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ACUTE  CONTAGIOUS  DISEASES. 


BY 

WILLIAM  M.  WELCH,  M.D., 

DIAtiNOS'ilCIAN    TO   THli    BUREAU  OIC  HEALTH  AND    CONSULTING    PHYSICIAN  TO  THE    PHILADKLPHIA 

MUNICIPAL   HOSPITAL  FOR   CONTAGIOUS    AND   INFECTIOUS    DISEASES;    FOR  THIKTY-THREK 

YEARS    PHYSICIAN-IN-CHARGE    OF   THE    MUNICIPAL   HOSPITAL;    FELLOW   OF 

THE    COLLEGE    OF    PHYSICIANS    OF   PHILADELPHIA; 


AND 


JAY  F.  SOHAMBERG,  A.B.,  M.D., 

PROFESSOR    OF    DERMATOLOGY    AND    OF    INFECTIOUS    ERUPTIVE    DISEASES,    PHILADELPHIA    POLY- 
CLINIC  AND   COLLEGE   FOR   GRADUATES   IN   MEDICINE;    ASSISTANT    DIAGNOSTICIAN   TO 
THE   BUREAU    OP   HEALTH  AND   CONSULTING   PHYSICIAN  TO  THE   MUNICIPAL 
^  HOSPITAL  FOR   CONTAGIOUS   AND   INFECTIOUS    DISEASES;    FELLOW 

OF   THE   COLLEGE    OF   PHYSICIANS    OF   PHILADELPHIA; 
MEMBER  OF  THE  AMERICAN  DERMATOLOGICAL 
ASSOCIATION. 


ILLUSTRATED  WITH   109   ENGRAVINGS  AND    61    FULL-PAGE    PLATES. 


LEA  BROTHERS  &  CO., 

PHILADELPHIA     AND     NEW    YORK. 
1905. 


Entered  according  to  the  Act  of  Congress,  in  the  3'ear  1905,  by 

LEA  BROTHERS   &   CO., 
In  the  Office  of  the  Librarian  of  Congress.     All  rights  reserved. 


DOEN.'VN,    PRINTER. 


PREFACE. 


In  this  work  on  Acute  Contagious  Diseases  the  writers  have  endeav- 
ored to  present  a  practical  treatise  for  the  guidance  of  students  and 
practitioners  of  medicine. 

Perhaps  some  explanation  may  be  sought  for  the  adoption  of  the 
title.  We  have  somewhat  arbitrarily  included  in  this  work  but  a 
small  group  of  diseases,  particularly  those  with  which  we  have  had 
experience  in  the  Municipal  Hospital  of  Philadelphia.  The  use  of  the 
term  "infectious  diseases"  would  have  necessitated  the  inclusion  of  a 
great  number  of  maladies  upon  which  we  do  not  feel  specially  qualified 
to  write.  Furthermore,  the  group  of  contagious  diseases  is  distin- 
guished by  great  transmissibility,  being  communicated  by  the  merest 
contact  or  even  by  proximity,  and  therefore  the  term  in  its  strict 
etymological  sense  appears  to  us  to  be  justified.  Vaccinia  is,  of  course, 
not  contagious,  but  its  relation  to  the  prophylaxis  of  smallpox  makes 
the   consideration   of  the  two  inseparable. 

The  comparative  infrequency  of  epidemics  of  smallpox  renders  it 
quite  possible  for  accomplished  and  otherwise  experienced  physicians 
to  be  somewhat  unfamiliar  with  this  disease.  We  have,  therefore, 
devoted  to  this  affection,  and  particularly  to  its  diagnosis,  an  amount 
of  space  not  usually  accorded  to  it  in  text-books  of  medicine. 

We  have  furthermore  endeavored  to  elucidate  the  subject-matter 
with  numerous  photographs  of  patients  under  our  care.  The  text  is 
based  upon  a  personal  study  of  over  9000  cases  of  smallpox,  9000 
cases  of  scarlet  fever,  and  10,000  cases  of  diphtheria,  in  addition  to 
a  considerable  number  of  cases  of  the  other  diseases  discussed,  all  of 
which  have  been  treated  in  the  Municipal  Hospital  of  Philadelphia 
during  the  past  thirty-five  years. 


vi  PREFACE 

We  desire  to  acknowledge  our  indebtedness  to  Dr.  E.  L.  Graf, 
formerly  Resident  Physician  in  the  Municipal  Hospital,  for  assist- 
ance in  securing  some  of  the  photographs;  to  Dr.  Burton  K.  Chance, 
for  the  contribution  of  the  chapters  on  Eye  Complications  and  Treat- 
ment in  Variola;  and  to  the  publishers^  Lea  Brothers  &  Co.,  for  the 
uniform  courtesy  extended  to  us. 

W.  M.  W. 

Philadelphia,  Mat,  1905.  t     xri     o 

J.    r.    o. 


CONTENTS. 


CllAVlTAi   I. 

PAGE 

Vaccinia 17 

CHAPTER  II. 
The  Relationship  oi-  Cowpox  or  Vaccinia  to  Smallpox 87 

CHAPTER  III. 
The  Variolous  Diseases  of  Lower  Animals 135 

CHAPTER  IV. 
Smallpox         144 

CHAPTER  V. 
Complications  and  Sequels  of  Smallpox 229 

CHAPTER  VI. 
Chickenpox 316 

CHAPTER  VII. 
Scarlet  Fever 341 

CHAPTER  VIII. 
The  Diagnosis  of  Scarlet  Fever 447 

CHAPTER  IX. 
Measles 476 


,•;;  CONTENTS 

VUl 

CHAPTER  X. 

PAGE 

547 

Rubella 


CHAPTER  XI. 
Typhus  Fever 

CHAPTER  Xn. 

....     598 
Diphtheria 

CHAPTER  Xni. 
The  Treatment  of  Diphtheria 

CHAPTER  XIV. 
The  Serum  Treatment  of  Diphtheria 730 

CHAPTER  XV. 
Disinfection        


(MIAPTER    r. 


VACCINIA. 


Synonyms. ^ — Latin,  vaccinia,  or  variola  vaccina;  fJenner);  P^nglish, 
cowpox  or  Jcinepox;  French,  la  vaccine;  German,  Kuhpocken, 
ImpfpocJcen,  Schutzbldttern;  Italian,  vaccinia;  Spanish,  vacuna. 

Definition. — Vaccinia  is  a  disease  commiinical^le  only  by  inocula- 
tion, and  is  characterized  by  one  or  more  skin  lesions,  accordinf(  to  the 
number  of  insertions  of  the  specific  virus,  running  through  the  stages 
of  papulation,  vesiculation  and  pustulation,  ending  in  desiccation  and 
falling  of  the  crusts  at  the  end  of  the  third  week.  The  process  is  attended  * 
by  slight  febrile  disturbance,  and  when  completed  confers  immunity 
against  smallpox. 

History.— When  Edward  Jenner  was  pursuing  his  professional  studies 
with  his  master  at  Sodbury,  a  young  country  woman,  on  hearing  small- 
pox mentioned,  immediately  observed,  "I  cannot  take  that  disease, 
for  I  have  had  the  cowpox."  This  incident  created  a  deep  impression 
in  the  mind  of  the  young  medical  student,  and  may  be  said  to  have  been 
the  awakening  impulse,  which,  after  years  of  patient  study  and  experi- 
ment, culminated  in  a  discovery  which  has  conferred  the  greatest  bene- 
fits upon  the  human  race. 

To  properly  appreciate  the  life-saving  value  of  Jenner's  discovery 
it  is  necessary  to  know  something  of  the  fearful  mortality  of  smallpox 
in  the  prevaccination  days.  It  was  the  most  dreadful  of  all  scourges, 
not  excluding  the  plague,  for  that  disease  came  but  rarely,  while  small- 
pox was  always  present.  Admiral  Berkeley,  chairman  of  the  committee 
of  the  House  of  Commons  (in  1S02)  to  investigate  the  petition  of  Jenner 
for  a  Parliamentary  grant,  in  an  elociuent  speech  said:^  "The  discovery 
of  Dr.  Jenner  is  unquestionably  the  greatest  discovery  ever  made  for 
the  preservation  of  the  human  species.  It  is  proved  that  in  these  united 
kingdoms  alone  45,000  persons  die  annually  of  the  smallpox;  but  through- 
out the  world  what  is  it?  Not  a  second  is  struck  by  the  hand  of  time 
but  a  victim  is  sacrificed  at  the  altar  of  that  most  horrible  of  all  dis- 
orders, the  smallpox." 

King  Frederick  William  III.  of  Prussia  stated  in  1803  that  40,000 
people  succumbed  annually  to  smallpox  in  his  kingdom.  The  French 
Minister  of  the  Interior,  in  reporting  on  vaccination  in  1811,  estimated 
that    150,000  persons   died   annually    in    France   from   smallpox.      In 

'  Quoted  by  Baron.    Baron's  Life  of  Jenner. 
2 


18  VACCINIA 

Russia  smallpox  is  reported  to  have  destroyed  2,000,000  lives  in  a 
single  year.^ 

The  mathematician,  BernouilK,  calculated  that  not  less  than  15,000,000 
human  beings  died  of  smallpox  every  twenty-five  years,  which  would 
give  a  yearly  average  of  600,000.  Dr.  Lettsom  estimated  that  Europe 
alone  claimed  210,000  victims  each  year.  When  to  this  number  are 
added  the  deaths  produced  by  devastating  epidemics  in  Asia,  Africa, 
and  America,  the  aggregate  estimate  mentioned  is  seen  to  be  conser- 
vative. The  early  records  of  the  London  Asylum  for  the  indigent  blind 
showed  that  three-quarters  of  the  inmates  had  lost  their  sight  through 
smallpox.^  De  la  Condamine  says  that  this  disease  destroyed,  maimed, 
or  disfigured  the  fourth  part  of  mankind. 

Traditions  Concerning  Cowpox  Protection. — The  fact  that  cowpox  con- 
ferred protection  against  smallpox  appears  to  have  been  noticed  by 
dairymen  in  England  as  far  back  as  the  middle  of  the  eighteenth  cen- 
tury. It  was  observed  by  these  people  that  when  smallpox  prevailed, 
those  who  had  been  accidentally  infected  by  the  matter  exuding  from 
certain  sores,  known  as  cowpox,  which  often  appeared  on  the  teats 
•  and  udders  of  cows,  resisted  the  infection  of  smallpox. 

It  is  said  that  Benjamin  Jesty,  a  Yetminster  farmer,  was  the  first 
person  in  England  to  employ  cowpox  virus  for  the  purpose  of  protecting 
against  smallpox.  In  1774  he  vaccinated  his  wife  and  children  with 
matter  taken  from  the  teats  of  cows  that  had  the  cowpox.  In  about  a 
week  the  arms  became  inflamed  and  considerable  constitutional  dis- 
turbance was  present.  The  children  were  later  inoculated  with  small- 
pox matter  without  result. 

In  Germany  the  protective  influence  of  cowpox  was  known  and  prac- 
tised prior  to  this  date.  Jobst  Bose,  a  government  official,  called  atten- 
tion (General  Conversations  of  Gottingen,  part  39,  May  24,  1769)  to  the 
fact  that  the  protection  conferred  by  cowpox  against  smallpox  was 
recognized  by  reputable  persons.  He  says:  "I  am  reminded  of  the 
not  unknown  attacks  of  cowpox  which  were  prevalent  in  this  country, 
and  to  which  to  this  day  milkmaids  are  subject.  In  passing  I  wish  to 
remark  that,  in  this  country,  those  who  have  had  the  cowpox  flatter 
themselves  to  be  entirely  free  from  all  danger  of  getting  smallpox,  and 
assert,  as  I  myself,  to  have  heard  this  same  statement  made  by  entirely 
reliable  persons."^ 

In  1791  a  school  teacher  by  the  name  of  Piatt,  who  lived  in  Starken- 
dorf,  near  Kiel,  vaccinated  several  children  of  his  landlord  to  protect 
them  against  a  prevailing  epidemic  of  smallpox.  Several  years  later 
they  escaped  smallpox,  although  intimately  exposed  to  the  disease.  He 
was  prompted  to  perform  this  procedure  by  the  popular  belief  concern- 
ing cowpox  protection  that  prevailed  in  Saxony  and  in  Holstein.     A 

1  Woodville  on  Smallpox.    Quoted  by  Baron. 

2  According  to  Sir  William  Aitken  90  per  cent,  of  the  cases  of  blindness  met  with  in  the  bazaars  in 
India  are  due  to  same  disease. 

3  Quoted  by  Kubler,  History  of  Smallpox  and  Vaccination,  Berlin,  1901.    Kubler  states  that  the 
writer  of  the  above  commentaries  was  a  man  with  practical  experience  in  farming. 


DISaOV/'^RV  OF  VAC'CTNATfON  19 

Holstein  fanner,  JeiiscMi  by  iiuine,  is  also  said  to  have  etii{)lrjyed  prophy- 
lactic cowpox  inoculation. 

The  same  tradition,  according  to  Humboldt,  existed  in  certain  parts 
of  Mexico  for  many  years,  and  similar  statements  are  made  concerning 
this  belief  in  Baluchistan. 

But  it  remained  for  Jenner  to  crystallize  this  half -forgotten  tradition 
into  a  scientific  theory,  and  then,  by  painstiiking  study  and  experiment, 
to  establish  its  truth  and  prove  it  to  the  world. 

Referring  to  the  vaccinations  performed  prior  to  -Tenner's  time,  Dr. 
Baron  says:  "They  did  not  advance  the  knowledge  or  the  practice  of 
vaccination  beyond  what  casual  observation  and  popular  rumor  had 
rendered  common  in  many  districts;  if  indeed  they  ever  took  place 
(which  I  think  more  than  doubtful)  they  were  quite  unknown  to  Dr. 
Jenner,  and  had  it  not  been  for  his  publication  they  never  would  have 
been  drawn  forth  from  their  obscurity." 

Early  Practice  in  England. — Edward  Jenner  was  born  in  the  vicarage 
at  Berkeley,  in  Gloucestershire,  in  1749.  He  was  the  third  son  of  Stephen 
Jenner,  rector  of  Rockhampton  and  vicar  of  Berkeley.  He  exhibited 
an  early  taste  for  natural  history,  and  as  a  boy  interested  himself  in 
zoology  and  geology.  After  his  scholastic  education  was  finished  he 
removed  to  Sodbury,  where  he  became  apprenticed  to  Mr.  Ludlow,  an 
eminent  surgeon  there,  to  be  instructed  in  surgery  and  pharmacy. 
In  1770  he  went  to  London  to  study  medicine  under  the  direction  of 
the  celebrated  John  Hunter,  with  whom  he  lived  for  two  years. 

In  1778  Jenner  won  the  fellowship  of  the  Royal  Society,  chiefly 
through  his  admirable  essay  On  the  Natural  History  of  the  Cuckoo. 
Despite  his  studies  in  natural  history,  the  tradition  concerning  cowpox 
gave  him  much  food  for  thought  and  was  frequently  mentioned  by 
him  in  conversation  with  his  friends. 

After  completing  his  course  in  medicine  and  locating  in  Berkeley, 
England,  where  dairy  farming  was  common,  Jenner  gave  close  atten- 
tion to  this  tradition,  and  it  was  not  long  until  he  was  convinced  of  its 
reality.  In  medical  coteries  and  societies  he  frequently  expressed  his 
belief  in  the  protective  power  of  cowpox,  but  his  views  on  this  subject 
were  always  regarded  by  his  confreres  as  idle  fancies  of  an  overcredii- 
lous  mind.  On  one  or  more  occasions,  in  a  certain  medical  society  to 
which  Jenner  was  a  liberal  contributor,  the  proposition  was  made,  half 
earnestly  and  half  jokingly,  to  expel  him  if  he  did  not  cease  boring 
them  with  his  absurd  notions  about  the  prophylactic  power  of  cowpox. 
But  the  evidence  he  had  already  collected  from  various  sources  was  too 
convincing  to  be  set  aside  by  such  idle  threats. 

At  length,  after  having  devoted  much  time  and  thought  to  the  sub- 
ject, Jenner  determined  to  inoculate  into  a  human  being  the  vaccine 
disease,  and  to  test  its  efficacy  by  actual  experimentation.  James 
Phipps,  a  lad  of  eight  years,  has  had  his  name  made  historical  by  ha%ing 
been  the  first  subject  to  undergo  the  experiment.  The  wus  used  was 
taken  from  a  vesicle  on  the  hand  of  a  milkmaid  named  Sarah  Xelms, 
who  had  been  accidentally  infected  while  milking  a  cow.    This  vaccina- 


20  VACCINIA 

tion  was  performed  May  14,  1796,  and  was  the  beginning  of  Jenner's 
work  which  has  made  his  name  immortal.  On  the  second  day  of  July 
following  Jenner  proceeded  to  test  the  efficacy  of  this  vaccination  by 
inoculating  the  lad  with  smallpox  matter  taken  from  a  patient  suffering 
from  that  disease,  but  no  result  followed.  At  various  intervals  after- 
ward, until  this  lad  grew  to  be  a  man,  he  was  inoculated  with  smallpox 
matter,  in  all  as  often  as  twenty  times,  and  each  time  was  found  to  be 
immune  to  that  disease.  It  is  no  wonder,  then,  that  Jenner  arrived  at 
the  conclusion  in  his  treatise  on  vaccinia  that  a  single  vaccination  con- 
fers permanent  immunity  from  smallpox. 

The  course  of  the  vaccine  disease  in  this  case  was  very  carefully 
noted  by  Jenner  each  day  fram  the  time  the  virus  was  introduced  until 
the  crust  came  off  spontaneously,  and,  finding  the  affection  was  benign 
and  wholly  unattended  by  unpleasant  results,  he  proceeded  to  subject 
others  to  the  "new  inoculation,"  as  vaccination  was  called  in  those  days. 
All  his  early  cases  were  subjected  to  the  same  crucial  test  that  was 
applied  in  the  case  of  James  Phipps,  to  prove  the  protective  power  of 
cowpox.  It  will  thus  be  seen  that  the  investigations  of  Jenner  were 
conducted  so  carefully  and  thoroughly  as  to  demonstrate  most  con- 
clusively the  value  of  his  discovery  before  he  ventured  to  publish  his 
observations  to  the  world.  Quoting  his  own  words:  "I  placed  it  on  a 
rock,  where  I  knew  it  would  be  immovable,  before  I  invited  the  public 
to  look  at  it." 

It  was  not,  therefore,  until  Jenner  felt  perfectly  secure  of  his  position 
that  he  ventured  to  detail  his  experiments  and  formulate  his  conclusions 
in  a  paper.  This  paper  was  prepared  in  1797.  It  was  Jenner's  inten- 
tion that  this  should  first  appear  in  the  Transactions  of  the  Royal  Society, 
but  this  design  was  abandoned  and  the  work  subsequently  appeared 
as  an  independent  publication.  In  1798  he  published  it  as  a  modest 
brochure,  entitled  An  Inquiry  into  the  Causes  and  Effects  of  the  Varioloe 
VaccincB,  a  Disease  Discovered  in  Some  of  the  Westerji  Counties  of 
England,  Particularly  Gloucestershire,  and  Known  by  the  Name  of  Cow- 
pox. 

This  publication  at  once  attracted  great  attention  from  the  medi- 
cal profession  in  London  and  throughout  England.  Like  all  innova- 
tions, the  "new  inoculation"  was  viewed  favorably  by  some,  with 
distrust  and  skepticism  by  others,  while  a  few  resolved  to  test  it  for 
themselves. 

Among  the  first  in  London  to  make  use  of  the  new  discovery  were 
Dr.  George  Pearson,  physician  to  St.  George's  Hospital,  and  Dr.  William 
Woodville,  physician  to  the  Smallpox  and  Inoculation  Hospital.  But 
the  early  work  of  these  gentlemen  tended  to  impair  confidence  in  vac- 
cination. They  reported  that  vaccinia  was  attended  with  a  generalized 
eruption  more  or  less  copious,  resembling  that  of  variola.  When  Jen- 
ner's attention  was  called  to  the  matter  he  denied  that  such  a  result 
followed  true  vaccinia,  and,  on  investigating  the  cases  presenting  this 
eruption,  he  found  that  Woodville  had  carelessly  permitted  the  virus 
which  he  and  Pearson  were  using  to  become  contaminated  with  the 


KAIUA'  IIISTOnV  OF   V/\  CCINA  T/0 \'  21 

infection  of  sinallpox.  A  coiisi(lorji})l(;  ((uuntify  of  lliis  virus  was  sent 
by  these  gentlemen  to  viirioiis  j),'irts  of  Eii/^land  aixl  tfic  C>)ntinent,  and 
in  many  instances  its  use  was  followed  by  disastrous  results.  Foreseeing 
that  vaccination  was  likely  to  be  (Jiseredit<!d  by  such  carelessness, 
.Tenner  remonstrated  against  their  proceciure  with  some  vehemence, 
but,  instead  of  being  listened  to,  was  rewarded  by  the  ill-will  of  Wood- 
ville  and  the  lifelong  enmity  of  Pearson. 

When  the  news  of  Jenner's  discovery  had  reached  the  various  civil- 
ized countries  of  the  world  he  became  literally  overwhelmed  with  corre- 
spondence. This  grew  to  such  immense  proportions  that  he  was  forced 
to  neglect  his  private  work.  He  was,  as  he  said,  for  many  years  the 
vaccine  clerk  of  the  world.  All  this  involved  a  large  expenditure  of 
money,  while  he  was  reaping  no  substantial  reward  from  his  discovery. 
Finding  that  his  small  fortune  was  rapidly  diminishing,  some  of  his 
friends  advised  him  to  make  application  to  the  British  Parliament  for 
an  honorarium.  His  claim  was  presented  and  ably  supported.  In 
the  discussion  it  was  contended  that  England  owed  to  this  worthy  citizen 
not  only  her  gratitude,  but  something  more  substantial,  in  consideration 
of  his  great  discovery,  which  had  already  been  the  means  of  saving 
thousands  of  lives  among  her  subjects,  and  had  prevented  untold  suffer- 
ing; and  that  the  author  of  which  was  magnanimous  enough  to  spend 
his  time  and  fortune  in  spreading  the  blessings  of  his  discovery  through- 
out the  entire  world.  The  claim  was  opposed  by  some  members  of 
Parliament  and  by  a  few  physicians,  who  should  have  been  friends  of 
the  claimant.  In  the  opposing  argument  it  was  contended  that  Jenner 
should  have  kept  his  discovery  a  secret  long  enough  to  grow  rich  by  it 
before  giving  it  to  the  world.  To  this  Jenner  replied:  "AYhile  I  had 
thus  been  employed  in  filling  my  own  purse,  should  I  not  have  indi- 
rectly been  filling  the  churchyard  with  those  slain  by  the  smallpox?" 
Surely  there  could  be  but  one  answer  to  this  question.  And  the  senti- 
ment it  contains  must  have  gone  very  far  toward  convincing  Parliament 
that  its  author  was  a  man  worthy  of  the  name  of  "great  benefactor," 
and  that  the  claims  made  for  him  as  such  could  not  be  lightly  set  aside. 

After  the  proposition  to  remunerate  Jenner  had  been  before  Parlia- 
ment a  long  time,  and  had  been  fully  considered  by  a  committee,  a 
grant  of  £10,000  was  voted  him.  This  occurred  in  1802.  But  con- 
siderable time  elapsed  before  the  money  was  paid,  and  its  collection 
cost  Jenner  £1000.  Feeling  that  this  grant  was  very  much  too  small 
for  a  great  country  like  England  to  bestow  upon  her  greatest  benefactor, 
Jenner's  friends  petitioned  Parliament  again  in  1807  for  a  secoiTd  grant 
of  £20,000.  By  this  time  the  value  of  his  discovery  was  better  known 
and  more  generally  appreciated,  so  that  this  grant  was  allowed  with 
much  less  opposition  than  the  first;  and  it  was  provided  in  the  act 
that  the  amount  should  be  promptly  paid  without  any  expense  to  the 
grantee. 

Jenner  labored  incessantly  to  disseminate  throughout  the  world  a 
correct  knowdedge  of  this  life-saving  agent.  In  1799  he  published 
Further   Observation   on  the   Variolce  Vaccincc,  or  Coicpox,  in  which 


22  VACCINIA 

he  carefully  pointed  out  the  difference  between  genuine  and  spurious 
cowpox. 

It  was  not  long  before  the  merit  of  Jenner's  discovery  was  universally 
admitted.  In  many  instances  the  crowned  heads  of  Europe  set  a  good 
example  by  promptly  accepting  vaccination,  and  very  soon  arrangements 
were  made  to  confer  its  blessings  on  the  peasantry  without  cost.  Honors 
were  freely  conferred  upon  Jenner  from  every  European  country,  and 
he  was  regarded  as  the  greatest  benefactor  the  world  had  ever  known. 
A  letter  from  him  served  as  the  best  passport  one  could  have  in  travel- 
ling through  foreign  countries  in  time  of  war.  As  showing  how  highly 
he  was  esteemed,  it  is  said  that  during  the  Napoleonic  war  two  British 
subjects  were  held  as  prisoners  by  Napoleon,  and  that  Jenner  was 
importuned  to  write  a  letter  requesting  their  release.  The  letter  was 
read  to  Napoleon  by  Josephine,  and  when  she  mentioned  the  name  of 
the  writer.  Napoleon  exclaimed:  "Jenner!  Oh,  we  can  refuse  nothing 
to  that  man."  And  the  prisoners  were  promptly  released  and  permitted 
to  return  to  England. 

The  Dowager  Empress  of  Russia,  Maria,  wrote  Jenner  a  most  com- 
plimentary letter  and  accompanied  it  with  the  gift  of  a  ring  set  in 
diamonds.  In  honor  of  the  discovery  she  gave  the  name  of  "  Vaccinoff  " 
to  the  first  child  vaccinated  in  the  Russian  Empire,  and  settled  an 
annuity  on  it  for  life. 

In  1821  Jenner  was  further  honored  by  being  appointed  physician 
extraordinary  to  the  King  of  Great  Britain. 

The  fame  of  Jenner  spread  throughout  the  entire  civilized  world. 
The  most  distinguished  scientific  bodies  vied  with  each  other  in  con- 
ferring honors  upon  him.  From  1801  to  1822  Jenner  received  no  less 
than  twenty-eight  diplomas  from  institutions  of  learning  and  scientific 
societies  in  every  country  of  Europe  and  in  the  United  States  and  Canada. 
Complimentary  addresses  were  sent  to  him  by  public  bodies  and  emi- 
nent individuals  in  every  part  of  the  world.  In  1803  the  corporation 
of  London  voted  Jenner  the  freedom  of  the  city,  which  was  presented 
to  him  in  a  golden  box.  In  the  several  succeeding  years,  Dublin,  Edin- 
burgh, Liverpool,  and  Glasgow  conferred  similar  honors  upon  the 
illustrious,  but  modest  physician. 

Within  a  period  of  six  years,  eight  medals  were  struck  in  Europe  in 
honor  of  the  great  discovery.  In  1804  one  of  the  most  beautiful  of  the 
Napoleonic  series  of  medals  appeared,  commemorative  of  the  emperor's 
estimate  of  the  value  of  vaccination. 

While  Jenner's  great  renown  rests  upon  the  discovery  and  introduc- 
tion of  vaccination,  he  is  to  be  credited  with  other  notable  scientific 
achievements,  which  would  in  themselves  have  entitled  another  to  dis- 
tinction. Dr.  Baron  briefly  summarizes  Jenner's  scientific  work  in 
directions  other  than  vaccination  in  this  language:  "In  conjunction 
with  Mr.  Hunter  he  carried  on  experiments  illustrative  of  the  structure 
and  functions  of  animals.  With  much  industry  and  ingenuity  he 
explained  one  of  the  most  unaccountable  problems  in  ornithology; 
he  ascertained  the  laws  which  regulate  the  migration  of  birds;  he  made 


KAIILY   VAddlNATION  IN  1)1  Fl'' I:I!I<:NT  COIfSTl! I ES  2:\ 

considerable  advances  in  geology,  ami  in  llic  knowlerlge  of  organic 
remains;  he  amended  several  pharmacciilicjil  j^rocesses;  he  was  an 
accurate  anatoinist  and  pathologist;  he  ex[)lained  the  cause  of  one  of 
the  most  painrui  Jiircctions  of  the  heart/  and  advanced  far  in  his  inves- 
tigations respecting  the  diseases  of  the  lymphatic  system,  and  the 
most  numerous  and  extensive  disorganizations  lo  which  animals  are 
liable." 

Jenner  died  of  an  a])oplectic  attack  on  .January  20,  1S2.':}.  Twelve 
days  before  he  expired  he  wrote:  ''My  opinion  of  vaccinatum  is  prcrisdy 
as  it  was  when  I  first  promvlrjatcd  the  discovery.  It  is  not  in  the  least 
strengthened  by  any  event  that  has  happened,  for  it  could  r/ain  no  strength; 
it  is  not  in  the  least  weakened,  for  if  the  failures  you  speak  of  had  not 
happened,  the  truth  of  my  assertions  respecting  those  coincidences  which 
occasioned  them  would  not  Jiave  hccn  made  oid." 

The  Early  Practice  of  Vaccination  in  Other  Countries.  Franch. — The 
practice  of  vaccination  had  traversed  the  wide  expanse  of  the  Atlantic 
and  was  in  vogue  in  America  before  it  was  employed  in  the  French 
capital.  Valentin  and  Desoteux  were  the  first  French  writers  to  call 
attention  to  the  subject.  CoUadon,  of  Geneva,  visited  Paris  on  his 
return  from  England,  and  vaccinated  some  patients  at  the  Salpetriere. 
These  vaccinations  were  unsuccessful.  The  failures  were,  however, 
unable  to  stem  the  growing  tide  of  popularity  of  the  new  inoculation. 
Dr.  Aubert  was  sent  to  London  in  1800,  as  the  representative  of  the 
National  Institute  and  School  of  Medicine,  to  obtain  all  possible  informa- 
tion and  to  secure  virus.  In  the  mean  time,  Liancourt  commenced  a 
subscription  to  establish  a  vaccine  institute,  and  secured  the  moral  and 
financial  support  of  Lucien  Bonaparte,  then  Secretary  of  the  Interior. 
In  January,  1800,  Dr.  Jenner's  publication  was  translated  into  French 
by  Count  de  la  Roque.  Five  years  later  Napoleon  demonstrated  his 
confidence  in  vaccination  by  ordering  all  soldiers  to  be  vaccinated  who 
had  not  passed  through  smallpox. 

Spain. — In  the  year  1800  the  practice  of  vaccination  reached  Spain, 
through  the  eflForts  of  Don  Francesco  Piguilem,  who  performed  the  first 
successful  vaccinations  in  December  of  that  year.  Dr.  Jenner's  "In- 
quiry" was  translated  into  Spanish  in  the  early  part  of  1801.  Spanish 
colonies  were  supplied  with  lymph  through  repeated  arm-to-arm  vac- 
cinations of  children  on  board  ships. 

India. — Jenner  endeavored  to  spread  the  benefits  of  his  discovery 
into  Asia  and  Africa.  He  sent  his  publications  and  large  supplies  of 
virus  to  India,  but  the  boat  carrying  these  was  lost  at  sea.  He  was 
about  to  start  a  subscription  to  send  another  vessel  when  he  received 
the  tidings  that  Dr.  De  Carro,  who  had  introduced  vaccination  into 


1  Jenner  refrained  from  publishing  his  ideas  on  the  subject  of  angina  pectoris  and  the  causative 
underlying  pathology  which  he  believed  to  be  calcification  of  the  coronary  arteries,  because  his 
friend  John  Hunter  was  beginning  to  present  symptoms  of  this  disease.  Jenner  communicated  his 
views  on  the  subject  to  Mr.  Cline  and  Mr.  Home,  but  these  gentlemen  did  not  seem  to  think  much 
of  them.  When  Hunter  died,  Home  wrote  to  Jenner  and  told  him  that  the  autopsy  proved  his  view 
to  be  correct. 


24  VACCINIA 

Vienna,  had  forwarded  vaccine  matter  from  that  city  to  Constantinople, 
and  thence  to  Bombay.  In  a  short  time  from  two  to  three  thousand 
children  were  vaccinated  in  the  latter  city. 

Italy. — ^To  Dr.  Louis  Sacco,  of  Milan,  belongs  the  credit  of  having 
been  one  of  the  earliest  and  most  successful  disciples  of  Jenner.  In 
1801  he  introduced  vaccination  into  the  Cisalpine  Republic,  which  gave 
authoritative  sanction  to  the  practice  and  made  him  Director  of  \ac- 
cination.  Sacco  labored  with  unwearied  activity,  and  in  a  few  years 
performed  over  20,000  vaccinations.  In  many  of  these  the  virus  was 
obtained  from  an  animal  with  natural  cowpox,  which  was  discovered 
in  Lombardy  after  a  prolonged  search. 

Sacco  was  a  warm  admirer  of  Jenner,  and  the  esteem  was  recipro- 
cated by  the  latter.  A  letter  written  to  Jenner  in  1801  by  Sacco  begins 
thus:  "It  is  to  the  genius  of  medicine,  to  the  favorite  child  of  nature, 
that  I  have  the  honor  to  write.  The  name  of  Jenner  will  be  always 
beloved  by  all  posterity,"  etc. 

Austria. — The  zeal  and  energy  of  Dr.  De  Carro  were  largely 
responsible  for  the  early  employment  of  vaccination  in  Vienna  (1799). 
Besides  being  influential  in  disseminating  this  practice  throughout 
other  countries,  De  Carro  interested  his  friend  Count  de  Salm,  who 
worked  for  the  cause  with  the  greatest  energy  and  activity.  This  phil- 
anthropic nobleman  distributed  virus  and  literature  gratuitously,  and 
held  out  rewards  to  physicians  who  performed  the  greatest  number  of 
vaccinations.  The  good  people  of  Brunn  erected  a  temple  which  was 
dedicated  to  Jenner,  and  in  which  they  annually  held  a  festival  to  cele- 
brate his  natal  day. 

Germany. — Jenner  sent  virus  to  Prussia  which  was  used  to  vaccinate 
the  Princess  Louisa.  The  admirable  example  set  by  the  royal  family 
excited  a  general  confidence  in  the  measure  and  led  to  its  widespread 
employment.  The  king  actively  interested  himeslf  in  vaccination,  and 
founded  a  Royal  Inoculation  Institute  in  Berlin  under  the  direction  of 
Dr.  Bremer.  The  latter  collected  funds  to  have  medals  struck  com- 
memorative of  Jenner's  discovery.  These  were  given  to  the  parents 
of  vaccinated  children  when  the  latter  were  brought  back  for  in- 
spection on  the  seventh  day.  In  1799  Ballhorn  and  Stromeyer  intro- 
duced vaccination  into  Hanover.  The  former  gentleman  translated 
Jenner's  work  into  the  German  language.  To  Bavaria  is  due  the  dis- 
tinction of  being  the  first  country  to  enforce  compulsory  vaccination 
(1807). 

Switzerland. — Vaccine  matter  was  carried  by  Dr.  Peschier  to  Geneva 
from  Vienna,  where  he  had  studied  the  process  under  De  Carro.  The 
physician  who  labored  most  earnestly  in  Geneva  in  the  cause  of  vac- 
cination was  Odier,  who  in  1801  wrote  a  memoir  on  the  subject  of 
cowpox. 

Russia. — In  1801  some  of  De  Carro's  ivory  points  and  threads  were 
sent  from  Breslau  to  Moscow,  where  the  Russian  court  was  assembled. 
Both  Emperor  Alexander  and  the  Dowager  Empress  evinced  a  keen 
interest   in   vaccination   and   energetically   promoted   its   employment, 


I'JARfjY   Vy\(!<!INATI()N  IN  AMI<:i:i('A  25 

The  esteem  in  wliich  the  empress  held  Jenrier  iriuy  he  jnd/^ed  fcom  the 
Following  gracious  cj)istle  sent  to  him  in  1X02: 

MONSIEIJU  jKNNKIt  : 

The  employment  of  vaccination  in  England  liavinj;  liad  the  greatest  atid  rnoHt  fully  atteKle'l 
success,  I  have  liastencd  lo  imitate  the  example  in  introducing  it  in  tlie  religiouH  cHtabliBlnnentH 
which  are  under  my  direction.  I  am  pleased  to  rei)ort  the  huccchs  of  my  attempt,  ami  to  acknowledge 
my  gratitude  to  him  who  has  rendered  this  Kiginil  service  to  humanity.  'J'hiH  motive  prompts  me, 
air,  to  present  to  you  the  accompanying  ring  as  an  evidence  of  my  sentiments  of  esteem  and  friend- 
ship, with  which  I  am 

Affectionately  yours, 

Makie. 
Pawlosk,  August  10,  1802. 

Denmark. — In  the  summer  of  ISO  I  Jenner  gave  some  vaccine  matter 
to  Dr.  Marcet  for  use  in  Copenhagen.  Ilis  majesty,  the  King  of  Den- 
mark, manifested  a  "personal  solicitude  for  the  welfare  of  his  people," 
and,  after  receiving  the  report  of  an  investigating  commi.ssion  on  the 
subject,  approved  of  all  of  the  regulations  suggested.  The  committee, 
of  which  Professor  Winslow  was  a  distinguished  and  active  member, 
recommended  legislation  the  enaction  of  which  stamped  out  smallpox 
in  Denmark  for  almost  twenty  years. 

America. — The  introduction  of  vaccination  into  this  country  marks 
an  epoch  of  great  importance.  Smallpox  had  been  present  here  almost 
from  our  earliest  history.  During  the  eighteenth  century  it  was  par- 
ticularly rife  in  certain  parts  of  the  United  States.  The  New  England 
States  attempted  to  prevent,  by  various  legislative  enactments,  the 
introduction  of  smallpox  into  that  section  of  the  country.  In  some  of 
these  States  variolous  inoculation — a  measure  commonly  practised 
during  the  middle  and  latter  part  of  the  eighteenth  century — was  pro- 
hibited by  law.  When  persons  residing  in  such  localities  wished  to 
avail  themselves  of  the  advantages  of  smallpox  inoculation  they  were  in 
the  habit  of  going  to  New  York  for  the  purpose  of  undergoing  the  dis- 
ease in  this  way,  and,  after  their  recovery,  returning  to  their  homes. 
There  was  some  inconvenience  and  considerable  expense  attending 
this  procedure,  but  it  was  deemed  wise  b}^  many  to  submit  to  this  rather 
than  run  the  risk  of  the  indiscriminate  introduction  of  smallpox  into 
those  States.  In  a  large  seaport  town,  however,  such  as  Boston,  where 
intercourse  with  foreign  countries  was  constant,  it  was  found  impossible 
to  exclude  the  disease  by  statutory  law,  so  that  the  people  of  that  city, 
thinking  they  would  relieve  themselves  of  the  anxiety  attending  the 
constant  risk  of  taking  smallpox  in  the  natural  way,  submitted  by  com- 
mon consent  on  one  occasion  to  a  general  inoculation.  In  order  that 
the  practice  of  inoculation  should  be  conducted  with  as  little  risk  as 
possible  of  the  disease  spreading  by  the  natural  transmission  of  infec- 
tion, Dr.  Benjamin  Waterhouse,  the  first  Professor  of  Theory  and  Prac- 
tice of  Medicine  in  Harvard  College,  published  important  rules  and 
regulations  governing  the  practice  of  the  smallpox  inoculation.  Having 
thus  been  engaged  in  considering  measures  for  restricting  the  spread 
of  smallpox,  it  is  not  surprising  that  this  physician  should  have  been 
the  first  to  urge  upon  the  citizens  of  Boston  the  acceptance  of  Jenner's 
discovery. 


26  VACCINIA 

Early  in  the  year  1799  Waterhouse  received  from  Lettsom,  of  England, 
a  copy  of  Jenner's  brochure  of  Variolce  Vaccinae,  and  he  became  at  once 
deeply  impressed  by  the  new  and  wonderful  facts  it  contained.  On 
March  12,  1799,  he  published  in  a  newspaper  of  Boston  a  short  com- 
munication, entitled  "Something  Curious  in  the  Medical  Line,"  in 
which  he  gave  a  brief  account  of  the  new  discovery,  referring  to  its  mar- 
vellous protective  power  against  smallpox,  and  predicting  the  incalculable 
benefits  that  the  citizens  of  his  own  town  and  country  would  derive  from 
it.  "But,"  says  Waterhouse,  "this  publication  shared  the  fate  of  most 
others  on  new  discoveries.  A  few  received  it  as  a  very  important  dis- 
covery, highly  interesting  to  humanity;  some  doubted  it;  others  observed 
that  wise  and  prudent  conduct  which  allows  them  to  condemn  or  applaud 
as  the  event  might  prove;  while  a  greater  number  absolutely  ridiculed  it 
as  one  of  those  whims  which  rise  to-day  and  to-morrow  are  no  more." 

Soon  after  this  Waterhouse  received  from  London  a  copy  of  Dr. 
Pearson's  book  (the  second  publication  on  vaccination)  entitled  An 
Inquiry  Concerning  the  History  of  the  Cowpox,  Principally  with  a  View 
of  Superseding  and  Extinguishing  Smallpox.  At  a  meeting  of  the 
American  Academy  of  Arts  and  Sciences,  held  in  the  University  Build- 
ing, and  presided  over  by  John  Adams,  then  President  of  the  United 
States,  Waterhouse  gave  an  account  of  the  "new  inoculation,"  read 
passages  from  Jenner's  publication,  and  recapitulated  from  Pearson's 
book  as  much  as  he  could  remember,  the  book  itself,  he  tells  us,  having 
been  loaned  and  lost.  The  membership  of  the  academy  included  the 
most  cultured  men  of  Boston,  and  the  communication  was  received 
with  interest  and  satisfaction  by  all;  but  none  manifested  so  great  an 
interest  as  the  illustrious  President  himself,  "  who,"  as  Waterhouse  says, 
"to  a  profound  erudition  in  letters  and  politics  joins  no  small  knowledge 
in  the  science  of  medicine." 

Before  the  next  quarterly  meeting  of  the  academy,  Waterhouse 
received  the  third  publication  on  the  subject  of  vaccination,  which  was 
from  the  pen  of  Dr.  William  Woodville,  physician  to  the  Smallpox 
Hospital  of  London.  This  publication  was  entitled  Reports  of  a  Series 
of  Inoculations  for  the  Variolce  Vaccinae,  or  Cowpox,  with  Remarks  and 
Observations  on  this  Disease,  Considered  as  a  Substitute  for  the  Small- 
pox. In  lieu  of  a  paper  which  he  had  been  asked  to  prepare  for  this 
meeting,  Waterhouse  read  extracts  from  this  publication.  Having  had 
as  yet  no  experience  in  vaccination,  not  even  having  seen  a  case,  he 
naturally  failed  to  recognize  the  almost  unpardonable  mistake  of 
Woodville.  In  his  publication  Woodville  states  that  a  large  number 
of  persons  whom  he  "vaccinated"  broke  out  during  the  course  of  the 
supposed  vaccine  disease  with  a  vesicular  eruption.  Some,  he  says, 
had  200,  some  300,  some  500,  and  a  few  had  from  1000  to  1500  vesicles. 
An  infant  at  the  breast  died  of  convulsions  on  the  eleventh  day  after 
the  "vaccine  matter"  had  been  inserted,  presenting  at  the  time  of  death 
from  80  to  100  vesicles.  The  explanation  of  this  unusual  phenomenon 
is  that  Woodville  first  vaccinated  a  number  of  persons  and  then,  three 
to  five  days  afterward,  inoculated  them  with  variolous  matter.     The 


EAIll^Y   VA(UJINAri()N  IN  AMKIirCA  27 

result  was  that  these  persons  were  affected  by  both  vaccinia  and  small- 
pox. Now,  it  was  tlie  virus  taken  from  this  sourr-e  that  produced  the 
eruption  in  the  cases  just  rt'ferrcd  to.  Tliis  m'n.cA  virus  was  (Jistril^uted 
freely  in  London  and  elscwlicre,  and,  as  already  staffed,  threatened  for 
a  time  the  re})utation  of  Jenner's  discovery.  Woodville  and  some  others 
regarded  this  generalized  eruption  as  peculiar  to  vaccinia. 

After  Waterhouse  had  collected  together  a  mass  of  evidence  in  sup- 
port of  the  efficacy  of  vaccination,  "too  great,"  as  he  says,  "to  be  resisted 
l)y  any  mind  not  perverted  by  prejudice,"  he  l)egan  to  seek  the  treasure. 
After  several  fruitless  attemj)ts  to  obtain  the  virus  in  an  active  state  from 
England,  he  at  length  received  some  from  Dr.  Haygarth,  of  Bath,  by 
a  short  passage  from  Bristol,  and  with  it  vaccinated  successfully  some  of 
the  younger  members  of  his  own  family.  This  virus  was  received  the 
latter  part  of  June,  LSOO,  and  on  July  Sth  he  vaccinated  one  of  his  sons, 
Daniel  OHver  Waterhouse,  aged  five  years.  So  far  as  existing  records 
show,  this  boy  was  the  first  person  vaccinated  in  America. 

Finding  that  the  course  of  vaccinia  in  this  child  was  typical,  as  com- 
pared with  Jenner's  description  of  the  disease,  he  then  vaccinated 
another  son,  aged  three  years,  with  virus  taken  from  the  arm  of  the 
first  child;  next  a  servant  boy,  aged  twelve  years,  with  some  of  the 
infected  thread  received  from  England;  then  an  infant,  one  year  old, 
and  its  nurse,  both  from  the  arm  of  the  two-year-old  boy.  A  few  of  the 
physicians  of  Boston  and  adjacent  towns  who  felt  an  interest  in  the 
matter  visited  the  subjects  for  the  purpose  of  learning  something  about 
the  new  disease.  The  visits  of  these  physicians  gave  rise  to  a  malicious 
report  that  one  of  the  Waterhouse  children  was  so  ill  from  the  "new 
inoculation"  as  to  require  a  consultation  of  several  members  of  the 
profession.  This  was  but  the  beginning  of  a  long  series  of  perversion 
of  facts  against  which  this  worthy  man  had  to  contend  in  his  work  of 
introducing  vaccination  into  Boston.  A  number  of  persons  now  applied 
to  Waterhouse  for  the  benefits  of  vaccination,  but  he  declined  to  vac- 
cinate anyone  residing  outside  of  Cambridge  until  he  had  proved  that 
this  new  agent  conferred  protection  against  smallpox.  He  determined 
therefore  to  subject  his  children  to  smallpox  inoculation. 

Dr.  Aspinwall,  who  was  the  physician  in  charge  of  the  Smallpox 
Hospital,  at  once  signified  his  willingness  to  assist  in  the  experiment, 
and  about  two  months  after  the  vaccination  of  Waterhouse's  children 
they  were  sent  to  the  hospital  and  not  only  freely  exposed  to  the  infec- 
tion of  smallpox,  but  also  inoculated  with  fresh  matter  taken  from  a 
patient.  Finding  the  children  resisted  the  disease  absolutely  when 
subjected  to  this  most  crucial  test,  Waterhouse  exclaimed:  "One  fact 
in  such  cases  is  worth  a  thousand  arguments." 

Having  now  proved  that  vaccinia  confers  protection  against  small- 
pox, Waterhouse  was  ready  and  anxious  to  extend  its  benefits  as  widely 
as  possible.  He  labored  earnestly  and  persistently  for  the  abolishment 
of  smallpox  inoculation,  which  was  then  commonly  practised,  and  the 
adoption  of  vaccination  in  its  stead.  While  he  recognized' the  fact  that 
inoculation  had  robbed  smallpox  of  very  many  of  its  terrors,  yet,  like 


28  VACCINIA 

Jenner,  he  looked  confidently  to  vaccination  to  effect  its  entire  exter-"* 
mination.     For  the  purpose  of  showing  the  public  the  danger  from 
smallpox,   the   benefit  of  smallpox  inoculation,   and   the   still  greater 
benefit  of  vaccination,  he  published  in  the  Columbian  Sentinel  a  com- 
parative view,  somewhat  figuratively  stated.     Thus: 

Natural  Smallpox.  Inoculated  Smallpox.  Kinepox. 

"  A  contagious  disease ;  1  in  "Contagious  ;  1  in  300  dies."  "Non-contagious;      never 

6  who  take  it  dies."  fatal." 

"  It  is  like  an  attempt  to  cross  "  It  is  like  crossing  the  stream  "  It  is  like  crossing  the  stream 

a  dangerous  stream  by  swim-  in  an  old  leaky  boat,  where  1  on  a  new  and  safe  bridge." 

ming,  where  1  in  6  perishes."  in  .300  perishes." 

Waterhouse  was  desirous  that  vaccination  should  at  first  be  placed 
only  in  careful  hands;  for  he  remembered  that  a  few  unsuccessful  cases 
at  the  beginning  of  smallpox  inoculation  in  Scotland  deprived  that 
country  of  the  benefits  of  this  measure  for  more  than  twenty  years. 

Jenner,  in  reply  to  a  letter  from  Waterhouse  informing  him  of  the 
deterioration  of  the  first  supply  of  virus,  and  detailing  certain  unfortu- 
nate experiences  in  the  hands  of  some  physicians,  wrote:  "I  do  not  care 
what  British  laws  the  Americans  discard,  so  that  they  stick  to  this — 
never  to  take  the  virus  from  a  vaccine  pustule  for  the  purpose  of  inocula- 
tion after  the  efflorescence  is  formed  around  it.  I  wish  this  efflorescence 
to  be  considered  as  a  sacred  boundary  over  which  the  lancet  should 
never  pass."  This  advice  was  so  constantly  given  by  Jenner,  and  was 
deemed  of  so  great  importance  by  him,  that  it  became  known  every- 
where as  the  "Golden  Rule"  of  vaccination. 

Early  in  the  spring  of  1801  Waterhouse  received  fresh  supplies  of 
virus  from  Jenner,  Lettsom,  and  other  friends  in  England.  With  addi- 
tional information  and  fresh  virus  he  began  vaccinating  again,  and  was 
rejoiced  to  find  that  the  vaccine  disease  presented  all  the  characteristics 
of  the  first  case  in  his  own  family.  He  was  now  anxious  that  the  benefits 
of  vaccination  should  be  difi'used  throughout  this  entire  country.  As 
he  had  received  some  months  before  a  letter  from  Thomas  Jefferson, 
President  of  the  United  States,  in  which  this  high  dignitary  manifested 
considerable  interest  in  the  subject,  Waterhouse  concluded  that  if  the 
Chief  Magistrate  of  the  nation  could  be  induced  to  take  hold  of  the 
matter,  vaccination  would  be  introduced  into  the  South  more  speedily 
and  safely  than  by  any  other  agency.  The  letter  of  the  President  con- 
tained not  only  an  acknowledgment  of  the  receipt  of  Waterhouse's 
pamphlet  on  the  subject  of  cowpox,  but  a  very  complimentary  refer- 
ence to  his  humane  work.    The  letter  read  as  follows : 

Washington,  December  25th,  1800. 

Sir  :  I  received  last  night,  and  I  have  read  with  great  satisfaction,  your  pamphlet  on  the 
subject  of  kinepock,  and  I  pray  you  to  accept  my  thanks  for  the  communication  of  it. 

I  had  before  attended  to  your  publications  on  the  subject  in  the  newspapers,  and  took  much 

interest  in  the  experiments  you  were  making.    Every  friend  of  humanity  must  look  with  pleasure 

upon  this  discovery  by  which  one  evil  more  is  withdrawn  from  the  condition  of  man,  and  must 

contemplate  the  possibility  that  new  improvements  and  discoveries  may  still  more  and  more  lessen 

the  catalogue  of  evils.    In  this  line  of  proceeding  you  deserve  well  of  your  country ;  and  I  pray  you 

accept  my  portion  of  the  tribute  due  you,  and  assurance  of  high  consideration  and  respect,  with 

which  I  am,  sir, 

Your  most  obedient,  humble  servant, 

Pr.  Waterhouse,  Cambridge.  Thomas  Jefferson. 


EAIU/Y   VAddlNATION  [N  AMEIiKJA  29 

In  j)ur,su!Uicc  of"  liis  purpose,  Watcrhoiisf;  fcjr\v;ir<lcfl  Iodic  IVcsidf-nf , 
June  8,  ISO],  some  virus,  toi^c^tlior  witli  hooks  aiuJ  drawiu^^s  <l(;scrif>tive 
of  vaccinia,  and  recpiested  that  they  he  ^iveri  to  sf>nie  careful  and  dis- 
cerning practitioner — to  his  own  family  physician,  if  he  preferred.  He 
also  sent  a  lengthy  letter  full  of  instruction  as  to  the  use  f)f  the  virus, 
and  courteously  reim"nded  the  ('resident  that  amidst  the  pelting  storms 
of  his  adversaries  Jenner  had  the  countenance  of  his  sovereign;  that 
the  Duke  of  York  v\^as  a  patron  of  the  London  Vaccine  Institution;  that 
Bonaparte  took  a  lively  interest  in  the  dissemination  of  vaccination  in 
France,  and  so  did  the  German  nobility  at  the  Court  of  Vienna.  He 
e.xpressed  the  hope  that  the  President  of  the  United  States  would  lend 
his  influence  to  extend  the  blessings  of  the  new  discovery  to  the  Middle 
and  Southern  States,  believing,  as  he  said,  if  it  came  from  the  hands 
of  the  Chief  Executive  of  the  nation  it  would  make  a  greater  and  more 
favorable  impression  on  the  minds  of  the  public. 

The  President's  reply  convinced  Waterhouse  that  he  had  made  Jio 
mistake  in  the  course  he  decided  upon.  The  virus  which  had  been  sent 
him  was  entrusted  to  a  judicious  and  successful  physician,  but  it  failed 
to  communicate  the  vaccine  disease.  So  also  did  the  second  and  even 
the  third  lot  sent  to  the  President  by  Waterhouse.  A  number  of  com- 
munications passed  between  these  gentlemen,  when  at  last  Jefferson 
suggested  that  as  the  weather  was  warm  the  virus  be  placed  in  a  small 
vial  hermetically  sealed,  and  that  this  vial  be  immersed  in  water  in  a 
larger  one,  which  must  also  be  hermeticallly  sealed.  The  virus  thus 
conveyed  was  used  on  some  members  of  the  President's  family  by  Dr. 
Wardlaw,  of  Monticello,  and  proved  successful.  This  occurred  August 
6,  1801.  From  his  own  family  the  President  supplied  Dr.  Gantt,  of 
Washington,  with  a  small  quantity  of  vaccine  matter,  and  thus  was  the 
seed  of  vaccination  planted  at  the  capital  of  the  United  States. 

All  apphcations  made  to  the  President  for  virus  received  his  careful 
attention.  To  him  belongs  the  honor  of  sowing  the  seed  of  vaccination 
not  only  in  the  District  of  Columbia,  but  in  Pennsylvania,  Maryland, 
Virginia,  and  the  States  farther  South.  He  studied  the  process  of 
vaccinia  so  carefully  that  he  was  able  to  advise  others  as  to  the  proper 
time  for  taking  the  virus.  This  period  he  fixed  at  eight  times  twenty- 
four  hours  from  the  date  of  vaccination.  His  advice  in  this  matter, 
we  regret  to  say,  was  frequently  disregarded  by  physicians,  who  be- 
lieved themselves  wiser  than  he,  but  never  Avithout  detriment  to  vaccin- 
ation. 

Waterhouse  had  the  satisfaction  of  knowing  that  the  virus  which 
first  proved  effective  in  New  York  City  came  from  him.  To  speak  more 
definitely,  it  was  taken  from  the  arm  of  Governor  Sargent's  domestic, 
who  had  been  vaccinated  in  Boston  by  Waterhouse,  and  thence  was 
inoculated  into  several  persons  in  New  York  City,  on  ]May  22,  1801,  by 
Dr.  Valentine  Seaman.  Vaccine  virus  first  reached  Philadelphia  in  an 
eft'ective  state  November  9, 1801.  It  was  forwarded  by  Jefferson,  through 
Mr.  John  Vaughan,  to  Dr.  John  Redman  Coxe,  and  was  accompanied 
by  a  personal  letter  from  the  President,  full  of  valuable  instruction  as 


30  VACCINIA 

to  its  proper  use.  The  first  person  who  is  said  to  have  been  successfully 
vaccinated  in  Philadelphia  was  Dr.  Coxe  himself. 

Soon  after  Jenner's  brochure  was  published  there  appeared  in  almost 
every  civilized  country  in  the  world  one  or  more  supporters  of  the  new 
discovery  who  adhered  more  faithfully  than  others  to  the  teachings  of 
the  master,  and  consequently  achieved  distinction  in  this  new  field  of 
beneficent  work. 

Waterhouse,  of  Boston;  Sacco,  of  Milan;  and  De  Carro,  of  Vienna, 
were  the  most  faithful  followers  of  Jenner.  Of  his  many  disciples, 
Waterhouse  was  probably  the  ablest  and  worthiest.  It  is,  perhaps,  not 
too  much  to  say  he  was  so  regarded  by  the  great  benefactor  himself. 
The  published  letters  of  Jenner  clearly  indicate  his  high  esteem  of  this 
disciple.  He  well  deserved  the  confidence  of  the  master;  for,  single 
handed  and  alone,  in  his  own  city,  he  faithfully  and  earnestly  defended 
and  vindicated  vaccination  against  the  ridicule  of  the  profession  and 
the  prejudice  of  the  public  for  seven  years,  or  until  conviction  became 
too  strong  for  argument,  and  theoretical  objections  were  forced  to  give 
way  to  stubborn  facts.  So  earnestly,  constantly,  and  successfully  did 
Waterhouse  devote  his  time  and  talent  to  the  dissemination  of  vaccina- 
tion in  this  country,  and  always  so  precisely  in  accordance  with  the 
teachings  of  Jenner,  that  he  received  the  complimentary  title  of  the 
"Jenner  of  America;"  not,  as  might  be  supposed,  by  favor  of  the  medi- 
cal profession  of  his  own  country,  but  by  the  unanimous  voice  of  the 
London  Medical  Society. 

THE  HYGIENE  OF  VACCINATION. 

In  order  that  a  vaccination  may  pursue  a  perfect  course  and  remain 
free  of  subsequent  complications  it  is  important  that  certain  precautions 
be  observed.  These  may  be  classified  as  follows:  Care  as  to  (1)  purity 
of  the  vaccine  virus;  (2)  condition  of  the  vaccinee;  (3)  asepsis  dur- 
ing insertion  of  the  virus;  (4)  subsequent  protection  of  the  vaccine 
lesion. 

Purity  of  Vaccine  Virus. — Vaccine  virus  may  be  of  human  or  bovine 
origin.  Within  recent  years  the  use  of  calf-lymph  has  become  generally 
and,  indeed,  almost  universally  adopted.  The  German  government^  in 
1884  passed  a  law  that  vaccinations  and  revaccinations  in  the  Empire 
of  Germany  be  performed  exclusively  with  animal  vaccine.^ 

Humanized  Virus.— In  cases  where  it  is  necessary  to  employ  human- 
ized lymph,  it  is  best  taken  from  a  vaccine  pock  from  the  fifth  to  the 
eighth  day.  Virus  should  only  be  used  from  a  perfect,  primary,  vaccine 
vesicle  containing  clear  or  opalescent  fluid.  Where  there  is  excessive 
inflammation  or  any  other  irregularity  present,  the  vaccinifer  should  be 
rejected.    The  employment  of  the  contents  of  lesions  which  have  become 

1  Resolution  of  the  Imperial  Vaccine  Commission  of  1884 ;  approval  of  the  resolution  by  the 
Bundesrath,  1885. 

-  In  Mexico  humanized  lymph  is  still  extensively  employed,  and  is  preferred  by  the  physicians  of 
that  country  to  bovine  virus. 


Till':  II  Yd  I  EN  K  OF   VACCINATION  31 

purulent  is  strongly  to  he  condemned.  Jcniicr's  dicfinii  \v;i.s  flujl  lympli 
should  never  he  taken  from  a  lesion  after  the  fornuition  of  th(r  areola; 
this  he  regarded  as  the  "golden  rule  of  vaccination."  'I'he  vaccine 
crust  is  inferior  to  direct  arm-to-arm  vaccination  with  fhiiri  lymph. 
When  a  crust  is  employed  at  the  present  day  it  should  be  moistened 
v^ith  boiled  water  and  rubbed  up  upon  a  sterile  piece  of  glass. 

The  condition  of  health  of  the  vaccinifer  is  of  the  greatest  importance. 
When  humanized  virus  is  employed  careful  incjuiry  as  to  the  health  of 
the  parental  antecedents  should  be  made.  The  subject  from  whom 
the  vaccine  is  obtained  should  be  in  thoroughly  good  health.  The 
greatest  care  should  be  taken  to  determine  that  the  vaccinifer  is  free  of 
hereditary  syphilis.  While  the  transmission  of  this  disease  by  vaccina- 
tion is  extremely  rare,  its  possibility  is  sufficiently  well  established  to 
warrant  every  precaution  being  taken. 

It  is  the  custom  to  obtain  vaccine  virus  only  from  young  subjects; 
these  are,  of  course,  less  apt  to  be  suffering  from  certain  transmissible 
diseases.  It  is  well,  however,  that  the  infant  vaccinifer  should  have 
reached  the  age  of  six  months  or  thereabouts,  so  as  to  have  passed  the 
period  at  which  evidences  of  hereditary  syphilis  usually  make  their 
appearance. 

To  obtain  human  vaccine  lymph  the  vesicle,  after  having  been  pre- 
viously cleansed  with  soap  and  boiled  water,  should  be  punctured  in 
several  places  with  a  lancet  and  the  droplets  of  lymph  allowed  to  flow 
out.  These  are  then  transferred  upon  a  clean  lancet  to  the  individual 
about  to  be  vaccinated;  or  if  the  lymph  is  to  be  used  later  or  employed 
upon  some  one  at  a  distance,  it  may  be  collected  in  a  sterile  capillary 
tube.  After  the  vesicle  is  punctured  the  tube  is  thrust  through  the 
opening,  the  lymph  filling  the  tube  by  capillary  attraction.  When  it  is 
about  two-thirds  full  the  tube  is  withdrawn  and  the  ends  sealed  by 
heating  them  in  a  Bunsen  flame.  The  tubes  should  be  kept  in  a  cool 
place  until  used.  To  expel  the  lymph  from  the  tube  the  ends  should  be 
broken  off  and  the  fluid  blown  out  with  a  small  rubber  bulb. 

At  the  present  day  we  are  chiefly  concerned  with  hovine  lymph .  This 
material  is  employed  in  two  different  forms — as  a  lymph  and  as  a  vesicle 
pulp.  Lymph,  which  is  the  clear  fluid  contents  of  well-developed  vac- 
cine vesicles,  has  been  in  use  a  long  time.  Pulp,  which  is  a  combination 
of  the  lymph  and  the  interior  epithelial  structure  of  the  pock,  has  more 
recently  come  into  favor,  and  is  at  the  present  time  regarded  as  possessing 
greater  vaccinal  activity  than  the  clear  fluid.  Vaccine  lymph  is  used 
either  in  the  dry  form  upon  strips  of  ivory  or  celluloid  (so-called  "dry 
points")  or  in  sealed  capillary  tubes  in  the  form  of  a  glycerin  emulsion. 

There  is  a  growing  sentiment  among  the  best  observers  in  favor  of 
the  use  of  glycerinated  lymph.  This  form  of  lymph  has  the  sanction 
and  endorsement  of  the  British  Royal  Vaccination  Commission.  The 
method  of  preparation  of  dry  and  glycerinated  lymph  is  elsewhere 
considered. 

Condition  of  the  Vaccinee. — There  is  nothing  in  the  condition  of  a 
child  that  constitutes  a  sufficient  contraindication  to  the  performance 


32  VACCINIA 

of  vaccination,  if  there  be  liability  of  exposure  to  the  infection  of  small- 
pox. We  have  vaccinated  scores  of  children  suffering  from  scarlet  fever 
and  diphtheria  in  the  Municipal  Hospital  during  the  presence  on  the 
grounds  of  smallpox  cases.  We  have  never  seen  any  untoward  results 
from  vaccinating  these  patients,  but  the  vesicles  have  not  always  been 
as  perfect  as  we  would  have  liked  to  see  them. 

When  smallpox  is  not  prevalent  it  is  proper  for  physicians  to  exercise 
discretion  in  choosing  the  time  for  the  vaccination  of  an  infant.  There 
being  no  urgency,  the  medical  adviser  may  wait  until  the  child  has  reached 
a  favorable  age  and  is  in  good  condition  for  the  reception  of  the  vaccine 
disease. 

Age  of  Child. — In  order  that  the  proper  protection  against  smallpox 
may  be  granted  to  infants  it  is  advisable  that  they  should  be  vaccinated 
during  the  first  year  of  life.  The  vaccination  laws  of  Germany  require 
that  every  child  be  subjected  to  this  measure  before  the  expiration  of 
the  first  year  of  life,  unless  it  is  contraindicated  by  reason  of  poor  health. 
The  age  which  is  generally  considered  most  appropriate  is  between  Jour 
and  six  months,  for  at  this  period  the  child  has  not  yet  begun  to  be  dis- 
turbed by  the  process  of  dentition.  If  there  be  danger  of  smallpox 
there  is  no  reason  to  delay  because  of  the  tender  age  of  the  child.  We 
have  on  a  number  of  occasions  vaccinated  infants  immediately  upon 
their  appearance  into  the  world,  and  we  do  not  recall  any  bad  effects 
that  have  resulted  from  such  early  vaccinations.  Indeed,  we  have 
been  impressed  with  the  very  slight  degree  of  constitutional  disturbance 
that  has  attended  such  vaccinations.  Where,  however,  no  haste  is 
necessary,  we  deem  it  well  to  wait  for  several  months  until  the  child 
becomes  stronger  and  more  accustomed  to  its  mundane  environment. 

Health  of  the  Child .^ — It  is  best  to  delay  the  performance  of  vaccina- 
tion (provided  smallpox  be  not  prevalent)  if  the  child  is  poorly  nour- 
ished, or  suffering  from  diarrhoea  or  vomiting,  scrofulous  glands,  eczema, 
etc.,  or  if  the  infant  has  been  recently  weaned  or  placed  upon  some  new 
food.  Vaccination  of  such  children  is  prohibited  by  the  regulations  of 
the  English  Local  Government  Board.  In  general  terms  it  may  be 
said  that  when  smallpox  is  not  prevalent  the  physician  may  select 
such  time  for  the  vaccination  of  an  infant  as  may  find  it  in  the  best 
physical  condition. 

TECHNIQUE  OF  VACCINATION. 

Vaccination  being  in  a  sense  a  surgical  procedure,  its  performance 
must  be  guarded  by  those  precautions  of  asepsis  which  at  the  present 
time  apply  to  all  chirurgical  manipulations.  Laboratory  studies  and 
practical  experience  have  both  shown  that  even  in  the  most  trivial  of 
all  surgical  procedures — the  introduction  of  a  hypodermic  needle  into 
the  skin — certain  precautions  as  to  bacterial  cleanliness  are  necessary. 
Many  years  ago,  before  the  days  of  bacteriology,  this  truth  was  not 
known  and  consequently  proper  care  was  not,  as  a  rule,  observed  either 
in  surgery  or  in  the  practice  of  vaccination. 


TECIINIQIJI':  OF   VACfUNATION  \\\\ 

Asepsis.-  It  is,  of  course,  dcsirahlc  that  the  vaccine  lynipli  he  free 
of  foreign  bacteria.  In  oi'der  that  all  wcjurui  infections  niay  be  avcjifled 
it  is  advisable  that  the  arm  of  tlu;  vaccinae,  the  instrutiKint  to  be  em- 
ployed, and  the  hands  of  the  vaccinator  1)6  perfectly  clean.  Further- 
more, the  vaccine  vesicle  must  l)e  so  y)r()te(-ted  as  to  prevent  subsecjuent 
infection  at  the  site  of  vaccination. 

Disinfection  of  the  Skin.  Some  difference  of  ojjinion  exists  as  to 
the  thor()U(>;hness  with  which  disinfection  of  the  j)roj)()sed  vaccination 
area  should  be  carried  out.  Some  writers  urj^e  such  a  preparation  of 
the  skin  as  is  practised  prior  to  an  ordinary  surgical  operation.  Others 
believe  that  the  use  of  strong  antiseptics  is  to  be  avoifled,  inasmuch  as 
they  may  destroy  the  activity  of  the  vaccine  material  when  placed  upon 
the  skin. 

We  would  counsel  the  following  techni(jue:  It  is  advisable  for  the 
patient  to  take  a  tub  bath  on  or  before  the  day  on  which  the  vaccination 
is  to  be  performed,  and  to  put  on  clean  undergarments.  fUnfoitunately, 
it  is  difficult  to  have  these  measures  carried  out  in  the  very  people  who 
most  need  them.) 

The  vaccination  area,  usually  the  arm,  is  to  be  thoroughly  washed 
with  potash  soap  and  hot  water,  some  friction  being  used  so  as  to  dis- 
tend the  cutaneous  capillaries.  Personally,  we  prefer  to  follow  this 
cleansing  with  the  application  of  alcohol,  although  in  cleanly  persons 
this  is  perhaps  not  necessary.  The  arm  is  then  to  be  dried  with  sterile 
absorbent  cotton,  or,  when  this  is  not  available,  a  perfectly  clean  towel. 
The  operator  may  employ  an  ordinary  lancet  or  a  needle  to  produce 
the  necessary  abrasion.  If  the  former  is  used  it  should  be  previously 
disinfected  by  boiling,  immersion  in  an  antiseptic  solution,  or  thorough 
cleansing  with  soap  and  water  or  alcohol.  It  is  perhaps  better  to  employ 
a  needle  for  the  purpose,  inasmuch  as  a  new  and  clean  one  can  be  used 
for  each  vaccination. 

The  insertion  of  the  deltoid  muscle  is  the  site  usually  selected  for  the 
introduction  of  the  virus.  The  skin  is  made  tense  through  the  grasping 
of  the  inner  side  of  the  arm  with  the  left  hand.  The  epidermis  is  then 
abraded  over  an  area  of  a  third  or  a  half  inch;  this  is  done  either  by 
vertical  or  cross  scarification  with  a  needle  or  simple  scraping  with  a 
lancet  or  scalpel. 

It  is  important  that  the  ahrasion  he  not  too  deep.  The  drawing  of 
blood  is  to  be  avoided,  inasmuch  as  it  may  float  away  the  lymph  and 
prevent  absorption;  it  is  further  claimed  that  the  deep  scarification  is 
more  likely  to  be  followed  by  an  excessive  degree  of  inflammation.  It 
is  not  desirable  to  abrade  deeper  than  is  necessary  to  see  the  little  red- 
dish points  which  represent  the  loops  of  the  papillary  bloodvessels. 

It  is  a  matter  of  some  importance  to  rub  the  virus  well  into  the  abraded 
surface.  The  hasty  smearing  of  the  hiiiph  upon  the  arm  with  no  further 
manipulation  is  probably  responsible  for  a  certain  percentage  of  failures. 

Some  writers  have  advocated  vaccination  by  hypodermic  or,  rather, 
intradermic  puncture.  This  is  accomplished  by  expelling  the  iMnph  upon 
the  previously  cleansed  vaccination  site,  and  then  passing  a  thoroughly 


34  VACCINIA 

sterile  hypodermic  needle  obliquely  through  the  skin  over  this  area. 
Several  punctures  should  be  made  v^ithin  an  area  of  1  cm.  square,  but 
they  should  not  be  deep  enough  to  draw  blood.  The  puncture  carries 
the  lymph  into  the  skin.  The  alleged  advantage  that  little  or  no  scar 
results  from  this  method  appears  to  us  to  be  in  reality  a  disadvantage — 
for  the  presence  of  a  scar  and  its  character  constitute,  as  a  rule,  visible 
evidence  of  the  amount  of  protection  against  smallpox  which  the 
individual  enjoys.  We  therefore  see  no  special  advantage  of  this  over 
other  methods  of  vaccination. 

It  is  best  to  allow  the  lymph  to  dry  upon  the  arm  by  exposure  to  the 
air;  this  will  ordinarily  take  from  ten  to  thirty  minutes.  Where  it  is 
inconvenient  to  keep  the  arm  bared  for  this  time,  there  is  no  objection 
to  protecting  the  abraded  surface  for  a  few  hours  with  a  loosely  fitting 
shield  made  of  pressed  linen.  It  is  important  that  no  shield  should  be 
applied  which  congests  the  parts  by  peripheral  pressure  or  which  exerts 
any  suction. 

The  vaccine  vesicle  when  formed  should  be  sedulously  guarded 
against  mechanical  violence  or  injury.  Nature  provides  an  excellent 
protective  covering  for  the  vaccine  wound — a  hard,  concrete,  firmly 
attached  crust.  This  crust  is  formed  by  desiccation  of  the  vaccine 
pock.  When  the  vesicle  is  ruptured  by  traumatism,  some  of  the  con- 
tents escape  and  form  an  irregular,  friable  crust  which  is  easily  detached, 
leaving  an  open  wound  which  is  liable  to  infection  with  pathogenic 
organisms. 

Shields. — Various  forms  of  shields  have  been  devised  to  protect  the 
vaccine  lesion  from  injury  and  infection.  Many  of  these  have  failed 
utterly  of  their  purpose,  and  some  have  done  actual  injury  by  increasing 
the  inflammation,  and  by  rubbing  off  the  scabs  and  thus  producing 
open  sores.  Some  writers  condemn  all  shields;  we  have  seen  a  few 
made  of  a  light  metal  like  aluminum  which  appeared  to  protect  the 
vaccine  lesions  from  the  adhesion  of  the  sleeve  and  from  accidental 
injury  without  exerting  any  injurious  compression.  The  use  of  such  a 
shield,  which  can  be  easily  sterilized,  may  be  recommended.  The 
application  of  a  sterile  gauze  compress  over  the  vaccine  vesicle  is  also 
advocated;  there  is  no  objection  to  this  save  where  the  vesicle  becomes 
ruptured,  when  the  crust  will  adhere  to  the  gauze  and  be  torn  off  with 
its  removal. 

Patients  should  be  advised  not  to  allow  the  sleeve  of  the  shirt  or 
undershirt  to  rub  against  the  vaccine  vesicle.  It  is  often  a  good  plan 
to  have  a  thoroughly  clean  piece  of  linen  sewed  into  that  portion  of  the 
sleeve  which  comes  in  contact  with  the  vesicle.  Caution  should  be 
given  patients  against  rubbing,  scratching,  or  otherwise  fingering  the 
vaccination  scab;  manipulation  of  this  character  is  a  fertile  source  of 
ulceration  and  late  wound  infection. 

Number  of  Insertions. — It  is  the  custom  abroad  to  insert  the  lymph 
at  several  sites.  When  this  is  done  the  scarifications  should  not  be  too 
close,  for  fear  of  interfering  with  the  vitality  of  the  intervening  skin, 
thus  leading  to  sloughing.    It  is  best  to  allow  three-quarters  of  an  inch 


8YMPT0MH  AND  <!<)ITIISI<:  OF  VAdafNIA  ;"{5 

or  an  inch  of  licaltliy  skin  hciwccii  the  lesions,     in  lliis  foiiiifry  it  is  llic 
custom  to  make  but  a  siii^'lc  insertion. 

When  a  person  has  hccn  ('X])os('(l  jo  tlic  infection  of  snnillpox  it  is 
well  to  insert  lym])li  from  two  or  three  (iiU'erent  tubes  in  (hiVerent  phices, 
so  that  the  fullest  op|)ortunity  of  inducing  vaccinia  may  he  offered.  It 
is  better  that  the  patient  should  suffer  from  a  sore  arm  than  from  small- 
pox. 

SYMPTOMS  AND  COURSE  OF  VACCINIA. 

Vaccinia  in  the  human  subject  is  always  produced  by  inoculation. 
While  the  evolution  of  the  vaccine  lesion  is  a  more  or  less  constant  one, 
yet  a  certain  degree  of  variation  will  result  according;  as  the  vaccination 
is  performed  with  oi'iginal  cowj)o\  virus,  lono-  humanized,  or  heifer- 
transmitted   virus.     These  dift'erences  refer  rather  to   the  comparative 


Iiilant  born  ola  variolous  mother  in  the  .Municipal  Hospital.    Vaccinated  ou  day  of  birlh. 
Protection  complete.    Photographed  on  niiath  day. 

rapidity  of  the  process,  the  size  of  the  lesion,  and  the  character  of  the 
crust  and  the  resulting  scar,  than  to  any  deviation  in  the  evolution  of 
the  pock. 

During  the  first  two  or  three  days  after  the  insertion  of  the  vaccine 
virus  no  symptoms  are  observed  beyond  those  incident  to  the  slight 
abrasion  of  the  skin  made  by  the  operator's  lancet.  Ciw  thp_third  or 
fourth  day  very  faint  redness  may  be  seen  around  the  site  of  the  inocula- 
tion. This  redness  gradually  increases  while  at  the  same  time  a  dis- 
tinct papule  is  formed,  which  becomes  slightly  more  prominent  by 
increasing  in  area  rather  than  in  height. 

On  the  fifth  day  the  lesion  begins  to  be  vesicular.  This  is  usually 
observed  first  upon  the  margin  of  the  inoculated  area.  The  vesicle 
gradually  increases  in  size,  and  the  l^miph  that  it  contains  is  at  first  thin 
and  perfectly  transparent.     On  the  eighth  day  the  vesicle  reaches  its 


36 


VACCINIA 


greatest  perfection;  it  is  then  considerably  elevated  above  the  surface 
of  the  skin,  and  presents  a  "pearly"  appearance,  although  at  times 
the  vesicle  is  yellowish.  When  examined  closely  it  will  be  found  to 
have,  even  at  an  early  stage  of  its  development,  an  umbilicated  form 
similar  to  that  seen  in  the  vesicle  of  variola.  The  peripheral  portion  of 
the  vesicle  is  bulging  and  prominent,  whereas  the  centre  is  depressed. 
About  this  time  there  appears  around  the  vesicle  an  inflammatory 
band  or  areola.     This  is  most  intense  in  the  immediate  neighborhood 


Fig.  2 


Vaccine  vesicles  on  the  eigtith  day,  showing  little  or  no  surrounding  inflammation. 
Infant  vaccinated  at  birth,  owing  to  exposure  to  smallpox. 

of  the  vesicle,  gradually  merging  into  the  normally  tinted  skin.  During 
the  ninth  and  tenth  days  the  redness  increases;  streaks  of  redness 
often  extend  a  considerable  distance  from  the  lesion.  Occasionally 
the  cellular  tissue  becomes  involved  in  the  inflammatory  process,  pro- 
ducing a  swelling  and  hardness  of  the  skin  of  the  arm.  The  glands 
of  the  axilla,  when  the  vaccination  is  performed  upon  the  arm,  fre- 
quently become  enlarged  and  painful. 


SYMPTOMS  y\N I)  dOlJIlSK  OF   VA(J(!INIA 


37 


At  the  same  time  niild  consiitiitioii.'iJ  syinjjioins  iiuikc  llicii-  iippear- 
ance.  Slight  rigors  soiiictiitics  occur,  followed  by  niodcniU;  elevation 
of  tem{)eratiire.  It  is  not  often  tliat  tlu;  ternperatiin!  rises  more  than 
one,  two,  or  three  degrees  above  the  normal.  There  are  apt  to  he 
malaise,  impaired  appetite,  and  disturbed  sleep;  but  none  of  these 
symptoms  continue  very  long.  In  recording  very  carefully  the  consti- 
tutional disturbance  observed  in  his  first  case  of  induced  vaccinia, 
Jenner  says:  "On  the  seventh  day  he  (a  boy  aged  eight  years)  corn- 
plained  of  uneasiness  in  the  axilla,  and  on  the  ninth  he  became;  a  little 
chilly,  lost  his  appetite,  and  had  a  slight  headache.  During  the  wliole 
of  this  day  he  was  perceptibly  indisposed,  and  spent  the  night  with 
some  degree  of  restlessness,  but  on  the  following  (lay  he  was  perfectly 
well."  It  cannot  be  doubted,  however,  that  many  children  pass  through 
the  regular  course  of  vaccinia  without  any  apparent  systemic  disturb- 
ance; our  experience  leads  us  to 

believe  that  in  very  young  infants,  fk,-.  3 

particularly  those  but  a  few  weeks 
old,  the  febrile  reaction  is  less  pro- 
nounced than  in  older  children.  At 
times  both  the  constitutional  and 
local  symptoms  of  vaccinia  are 
very  severe,  especially  in  second- 
ary vaccinations. 

It  occasionally  happens  in  severe 
cases  of  primary  vaccinia  that  a 
cutaneous  eruption  appears  at 
about  the  tenth  day  of  the  disease. 
This  eruption  consists  of  a  macular 
erythema  similar  to  but  flatter  than 
the  measles  eruption.  The  efflor- 
escence may  be  comparatively 
limited  in  extent  or  it  may  cover 
almost  the  entire  body.  On  ac- 
count of  its  not  infrequent  associa- 
tion with  the  vaccine  process  it  has 
been  called  roseola  vaccinosa.  An 
analogous  and  almost  identical  eruption,  designated  roseola  I'ariolosa, 
is  occasionally  seen  in  modified  cases  of  smallpox  just  before  the  appear- 
ance of  the  papules.  These  eruptions  seldom  continue  longer  than  two 
or  three  days. 

On  the  eleventh  or  twelfth  day  of  the  vaccine  process,  the  pock  begins 
to  fade.  In  its  declining  stage  its  contents  become  opaque,  desiccation 
appears  in  its  centre,  and  the  areola  shades  of¥  into  two  or  three  con- 
centric circles,  varying  in  color  from  a  pale  red  to  a  deep  red  or  livid 
tinge. 

By  the  fifteenth  day  desiccation  is  usually  completed,  although  the 
crust  does  not  fall  off,  nor  can  it  be  easily  removed  until  the  end  of 
the  third  and  frequently  not  until  the  end  of  the  fourth  week. 


Vaccine  vesicle  upon  the  seventh  day ;  areola 
just  beginning. 


38 


VACCINIA 


The  completed  crust  is  of  a  mahogany  color,  rough  on  its  exterior, 
thin  at  its  centre  and  periphery,  with  a  thick,  circular  ridge  between. 
The  scar  is  at  first  red,  but  in  the  course  of  some  months  becomes  paler 
than  the  surrounding  skin.  It  is  pitted  or  foveolated,  and  not  infre- 
quently presents  an  elevated  centre  from  which  cicatricial  bands  radiate 
to  the  periphery.  A  perfectly  typical  scar  looks  as  if  it  had  been  stamped 
into  the  skin  with  a  sharply  cut  die. 

As  the  analogy  between  cowpox  and  smallpox  is  in  most  respects  very 
close,  and  as  variola  frequently  differs  in  the  duration  and  severity  of 
its  local  manifestations,  so  also  it  must  be  expected  that  the  local  lesions 


Flo.  4 


Vaccine  vesicle  upon  seventh  day,  showing  beginning  areola.    Patient  was  suffering  from 
scarlet  fever.    Vesicle  shows  some  irregularity  in  form. 

of  vaccinia  will  not  invariably  follow  the  typical  course  just  described. 
In  some  cases  the  course  of  the  disease  is  undoubtedly  shorter  and 
milder,  while  in  others  it  is  longer  and  more  severe.  It  is  essential, 
however,  that  the  pock  pass  through  the  stages  of  papule,  vesicle,  and 
pustule.  Likewise,  the  constitutional  symptoms  are  not  uniform;  they 
may  not  be  present  at  all,  or,  if  present,  may  be  so  mild  as  to  pass  unob- 
served. 

Tardy  Vaccinia. — Occasionally  a  retardation  of  the  vaccine  process 
is  observed;  usually  this  does  not  amount  to  more  than  a  delay  of  two 
or  three  days  in  the  development  of  the  vesicle.    In  such  cases  vesicula- 


SYMPTOMH  AND  (JOIIUSI'J  OF   VA(,'('/NIA  41 

A  tardy  development  of  tlu;  vaccine  lesion  orcuis  more  comnionly 
with  the  use  of  dry  virus  than  witli  a  licjuid  lymph.  A  rctai(l;itiofi  of 
cowpox  in  a  healthy  individual  docs  not  in  the  least  impair  its  protect- 
ive power  provided  it  runs  a  rej^ular  course.  It  is  evident,  liowever, 
that  a  tardy  development  of  the  vesicle  in  one  who  has  been  expo.sed 
to  smallpox  might  result  in  most  serious  consequences,  in  that  the  indi- 
vidual might  develop  variolous  symj)toms  before  the  vaccine  vesicle  is 
sufficiently  far  advanced  to  confer  protectit^n. 

Precocious  Vaccinia. — This  modification  of  the  normal  course  of 
vaccinia  is  much  rarer  than  retardation  of  the  process.  An  acceleration 
of  the  cow-pox  vesicle  occasionally  occurs,  the  development  being  has- 
tened by  twelve  or  twenty-four  hours.  In  such  cases  the  usual  appear- 
ances of  the  eight-day  pock  are  manifest  on  the  seventh  day.  These 
remarks  apply,  of  course,  to  primary  vaccinations;  in  secondary  vac- 
cinations the  process  is  not  infrequently  hastened  and  shortened. 

A  very  hasty  development  of  vaccinal  reaction  in  a  primary  vaccina- 
tion should  direct  attention  to  the  possibility  of  a  spurious  result,  as  such 
lesions  not  infrequently  appear  early  after  the  insertion  of  the  l}Tnph. 

Accessory  or  Supernumerary  Vesicles. — It  occasionally  happens  that 
a  moderate  number  of  supernumerary  pocks  are  seen  in  the  neighbor- 
hood of  the  vaccine  inoculation.  Whereas  but  one  abrasion  may  have 
been  made  upon  the  arm,  we  now^  and  then  observe  two  or  more  vaccine 
lesions  develop.  At  times  the  accessory  pocks  never  pass  beyond  the 
stage  of  papulation,  but  at  other  times  they  undergo  the  usual  evolu- 
tion. The  fact  that  such  additional  pocks  observe  a  predilection  for 
the  immediate  neighborhood  of  the  original  inoculation  suggests  that 
they  may  have  resulted  from  absorption  of  virus  through  minute  and 
unobserved  abrasions.  It  is  contended  by  some  writers  that  they  are 
due  to  transmission  of  the  virus  through  the  lymphatics,  inasmuch  as 
they  commonly  develop  at  a  time  when  the  primary  vaccine  vesicle 
begins  to  fill  with  lymph.  In  rare  cases  vesicles  may  develop  upon 
other  parts  of  the  body,  but  to  this  reference  will  be  made  later. 

Bryce's  Test:  Reinsertion  of  Vaccine  Matter  Five  Days  After  a 
Successful  Vaccination. — Bryce.  of  Edinhuro-h.^  demonstrated  the 
fact  that  a  fresh  insertion  of  lymph  made  at  any  period  not  later  than 
tlie_fiflh^iiay  from  the  successful  insertion  of  vaccine  virus  into  a  child's 
arm.  w;ould  take  effect  as  surely  as  if  no  previous  vaccination  had  been 
performed.  The  later  vesicles  will  overtake  in  their  course  the  vesicles 
first  made,  and  will  mature  and  fade  at  the  same  time  with  them, 
although  they  will  be  smaller  in  size.  For  instance,  if  some  active  vac- 
cine lymph  be  inoculated  four  or  five  days  after  a  first  vaccination, 
the  vesicles  of  the  second  insertion  will,  by  the  tenth  day  of  the  primary 
vaccination,  mature  and  be  surrounded  by  an  areola,  although  they  will 
have  but  the  size  of  a  five  or  a  six-day  vesicle.  If  the  second  insertion 
is  delayed  beyond  the  fifth  day,  there  will  be  either  no  result  at  all  or 
rnereiy  the  formation  of  a  hard  papule.     Bryce  advocated  the  practica 

i  Practical  Observations  on  the  Inoculation  of  tjie  Cowpox,  Edinburgh,  1S02  ;  second  edition,  1S09. 


42  VACCINIA 

employment  of  lymph  reinsertion  to  test  the  efficacy  of  the  protection 
conferred  by  the  original  vaccination.  He  argued  that  there  might 
be  a  perfect  local  vaccine  result,  without  such  a  systemic  impression  as 
to  confer  absolute  immunity  against  smallpox;  he  thought  that  by  the 
routine  reinoculation  of  lymph  on  the  fourth  or  fifth  day  the  existence 
of  the  constitutional  protection  might  be  tested.  This  practice,  which 
has  become  known  as  Bryce's  test,  has  not  been  accorded  much  endorse- 
ment, and  has  fallen  into  disuse.  It  has,  however,  a  scientific  interest, 
for  it  is  the  analogue  of  the  accidental  auto  vaccination  which  occurs  in 
natural  cowpox,  as  a  result  either  of  movements  of  the  cow  or  the  manip- 
ulations of  the  milker. 

Spurious  Vaccination.^It  is  deemed  necessary  to  refer  to  a  spurious 
variety  of  vaccine  lesion  which  has  grown  more  frequent  of  late  years, 
namely,  the  red  raspberry  excrescence,  as  it  is  commonly  termed.  This 
growth,  when  seen,  usually  appears  from  three  to  seven  days  after  the 
introduction  of  the  virus,  beginning  as  a  red  elevation  at  the  site  of 
inoculation,  quite  similar  in  appearance  to  the  papule  of  true  vaccinia, 
but  instead  of  advancing  to  the  vesicular  stage  it  remains  hard,  dense, 
bright  red  in  color,  and  nodular  in  form,  looking  not  unlike  a  small 
ncevus.  A  thin,  friable  crust  forms  on  its  surface,  but  when  this  is  removed 
the  lesion  continues  to  present  the  same  general  appearance  just  described. 
It  is  very  persistent,  remaining  usually  for  weeks  or  even  months;  no' 
areola  forms  around  it  at  any  time,  and  it  is  not  followed  by  a  scar. 

This  peculiar  excrescence  was  described  by  some  of  the  earlier  writers 
on  vaccination;  but  during  the  long  period  in  which  humanized  virus 
was  used  exclusively,  it  was  not  observed.  Since  the  introduction  and 
general  employment  of  animal  vaccine  virus  it  has  frequently  been 
seen.  It  seems,  therefore,  that  it  occurs  as  the  result  of  inoculating  the 
human  subject  with  some  unknown  form  of  inert  or  non-specific 
material,  taken  from  a  vaccinated  bovine  animal.  That  this  is  a  spurious 
form  of  the  vaccine  disease,  and  utterly  devoid  of  protective  power 
against  either  variola  or  vaccinia,  the  writers  have  had  ample  oppor- 
tunities of  proving. 

The  vaccine  vesicle  sometimes  runs  an  entirely  irregular  course.  In 
such  cases  it  begins  with  itching  and  irritation;  instead  of  being  flat 
and  umbilicated,  the  vesicle  is  acuminated  or  conical.  The  fluid  is 
commonly  opaque  or  yellowish  instead  of  being  a  clear  lymph;  as  a 
result  the  characteristic  pearly  lustre  of  the  vesicle  is  absent.  An  irregu- 
lar areola  often  develops  about  the  fifth  or  sixth  day;  several  days  earlier, 
therefore,  than  in  the  normal  vaccine  vesicle.  A  small  scab  forms 
which  usually  drops  off  about  the  tenth  day. 

Not  infrequently  the  vesicle  ruptures  early,  giving  issue  to  a  thin, 
yellowish  fluid  which  dries  in  the  form  of  a  friable  crust.  ^This  may 
become  detached  and  succeeded  by  a  second  crust,  which  results  as 
the  first  from  the  desiccation  of  the  exuding  material. 

wSometimes  the  local  reaction  is  less  pronounced,  the  site  of  vaccina- 
tion inflaming  early  and  scabbing  within  a  few  days,  so  that  at  the  end 
of  a  week  the  process  has  entirely  terminated. 


SYMPTOMS  AND  (lOrJUSK  OF   VAOdlNIA  48 

Bousquct,  ((noted  by  'i'rousscjiii,  ,sa,ys:  '"rriic  cowpox  liardly  hc^Miis 
to  show  itself  at  the  end  of  the  third  (hiy;  hnt  the  false  is  rnneJi  earher, 
and  may  be  seen  from  the  first  to  the  second  day  after  I  lie  intioduetifni 
of  the  virns,  a  circnmstanee  which  from  the  first  constitiite.s  a  distine- 
tion  between  the  two  aHVetions.  False  cowpox  sometimes  shows  itself 
as  a  sirnill  pimple,  which  o^ocs  on  increasing  nntil  the  fonrth  or  fifth  day. 
On  the  sixth  or  seventh  day  its  progress  becomes  arrested,  it  grows 
pale,  and  dries  up.  At  other  times  it  advances  farther,  always  pre- 
serving in  its  rapid  development  a  conical  or  globular  shape,  which  I 
look  upon  as  an  unerring  sign  of  false,  as  the  flattening  and  central 
(le})ression    of    the   pock   are    signs   specifically    charactei-istic    of    the 

true The   false    pock   is    sometimes    red    and    sometimes 

yellowish.     It  never  assumes  the  brilliant,  silvery  lustre  which  distin- 
guishes the  prophylactic  cowpock." 

Such  lesions  as  those  described,  of  course,  utterly  fail  to  give  any 
protection  against  smallpox.  Inaccurate  observers  have  not  infre- 
quently regarded  such  "sore  arms"  as  successful  vaccinations,  and 
have  been  surprised  to  see  such  individuals  later  contract  smallpox. 

We  have  on  several  occasions  observed  smallpox  develop  in  iiiflividuals 
who  have  had  local  reactions  which  were  regarded  by  themselves,  and 
in  several  instances  by  their  physicians,  as  genuine  "takes."  We  recall 
the  case  of  a  stout  woman  of  thirty  years,  who  had  been  vaccinated 
without  result  some  years  previously,  and  who  was  vaccinated  one 
month  before  admission  to  the  Municipal  Hospital.  She  informed  us 
that  there  had  been  some  local  reaction,  and  the  physician  in  attendance 
had  been  for  a  time  in  doubt  as  to  whether  there  had  been  a  successful 
"take"  or  not,  finally  deciding  in  the  negative.  The  patient  developed 
confluent  smallpox  and  died  in  ten  days.  From  an  examination  of  the 
arm  on  admission  we  were  convinced  that  the  result  had  been  spurious. 

A  young  man,  aged  twenty-five  years,  was  vaccinated  for  the  first 
time  about  Christmas  of  1901.  He  stated  that  the  vaccination  was 
inflammatory  from  the  outset.  A  vesicle  was  rapidly  formed,  and  later 
an  areola  and  axillary  tenderness  developed.  K  reddish  crust  remained 
upon  the  vaccine  site  for  a  period  of  three  weeks.  The  physician  in 
attendance  regarded  the  sore  as  a  genuine  "take."  The  patient  was 
admitted  to  the  hospital  on  February  6,  1902,  about  six  weeks  later, 
with  a  malignant  type  of  confluent  smallpox,  to  which  he  rapidly  suc- 
cumbed. Examination  of  the  arm  of  this  patient  upon  admission  to  the 
hospital  showed  a  brownish-red  stain,  but  no  scar  whatsoever.  In  this 
case,  in  which  the  vaccination  was  a  primary  one,  its  spurious  character 
was  evidenced  not  only  by  the  atypical  development  of  the  vesicle  and 
the  absence  of  a  characteristic  resulting  scar,  but  by  its  signal  failure 
to  protect  against  smallpox. 


44  VACCINIA 


INSUSCEPTIBILITY  TO  VACCINATION. 

Occasionally  persons  are  encountered  who  exhibit  an  insusceptibility 
to  the  virus  of  vaccinia.  The  number  is,  doubtless,  much  smaller  than 
is  commonly  believed,  for  one  or  tv^^o  unsuccessful  attempts  at  vaccina- 
tion are  often  construed  to  indicate  an  insusceptibility  to  the  infec- 
tion. 

Gregory  says:  "The  proportion  of  mankind  who  exhibit  this  singular 
idiosyncrasy  is  very  small.  I  have  seen  thirty  or  forty  such  cases  in 
the  course  of  my  life.  It  would  be  very  interesting  to  determine  whether 
this  constitutional  inaptitude  to  cowpox  denotes  a  like  inaptitude  to 
receive  and  develop  the  variolous  poison.  In  the  few  cases  which  I  have 
seen,  where  inoculation  was  subsequently  tried,  the  insusceptibility 
was  proved  to  extend  to  both  poisons,  but  I  have  read  of  instances  of 
an  opposite  kind."^ 

Of  upward  of  9000  vaccinations  performed  at  the  Blackfriars' 
station  of  the  National  Vaccine  Establishment  during  a  period  of 
about  ten  years  following  1859,  there  was  but  1  case  which  on  a  second 
trial  was  unsuccessful.  In  this  case  a  third  attempt  was  made,  but  the 
child  was  not  brought  back  for  inspection,  and  the  result,  therefore, 
could  not  be  ascertained.^ 

There  is  strong  reason  to  believe  that  a  person  may  be  immune  to 
vaccinia  at  one  period,  but  later  develop  a  susceptibility  to  the  vaccine 
disease.  Such  instances  of  temporary  absence  of  susceptibility  are  not 
particularly  rare.  Gregory  believed  that  such  failures  might  be  attrib- 
uted to  atony  of  the  absorbent  system  in  children  exhibiting  "slowness 
of  dentition,  imperfect  ossification  of  the  head,  emaciated  aspect  of  the 
body,"  etc.;  in  other  words,  evidence  of  rachitis. 

It  has  also  been  claimed  that  the  existence  of  certain  cutaneous  dis- 
eases, the  eruptive  fevers,  etc.,  produces  a  temporary  immunity  against 
vaccinia.  This  statement  scarcely  coincides  with  our  own  personal 
experience;  owing  to  the  fact  that  children  suffering  from  scarlet  fever 
and  diphtheria  are  treated  in  the  Philadelphia  Municipal  Hospital 
upon  the  same  grounds  as  the  smallpox  patients,  we  have  been  obliged 
to  vaccinate  scores  and  scores  of  such  patients.  We  have  found  that 
the  vaccination  is  received  almost  if  not  quite  as  uniformly  in  children 
with  scarlet  fever  and  diphtheria  as  in  those  enjoying  good  health. 

In  Scotland  (1864—65)  1  of  every  200  children  proved  refractory  to 
three  successive  vaccinations,  thus  entitling  them  to  a  certificate  of 
insusceptibility.  Doubtless  many  of  these  children  would  have  responded 
to  vaccination  had  it  been  tried  some  years  later. 

During  the  period  that  vaccination  was  performed  from  arm  to  arm, 
successes  were  so  uniform  that  a  person  who  resisted  three  attempts  on 
three  successive  weeks  was  assumed  to  be  temporarily  insusceptible. 
Such  an  inference  would  scarcely  be  warranted  with  the  employment 

1  Lectures  on  Eruptive  Fevers,  1851,  p.  244. 

2  Mentioned  by  Seaton,  Handbook  of  Vaccination,  1868,  p.  196. 


11 1<:  VA  aaiNA  ti  o  n  45 

of  bovine  lyinj)li,  piuiicul.'u-ly  when  used  in  n,  dry  sliitc  \)v.  Spalding, 
Chief  Medical  lnsj)ector  of  the  (Jhicu^'o  lioiinl  of  llejdf.h,  writes  that 
lie  has  known  eifjjht,  ten,  and  in  one  instance — in  the  j>ractice  (jf  a  col- 
leajijue — thirteen  attempts  at  vaccination  to  he  made  Ix-fore  a  snccessfnl 
result  was  obtained. 

Insusceptibility  to  vaccinia,  or  rather  failure  of  result  after  repeated 
attempts  to  vaccinate,  does  not  of  necessity  indicate  an  insusceptibility 
to  smallpox.  We  recall  to  mind  a  youn^  ])hysician  who  had  been 
repeatedly  vaccinated  in  childhood  aiul  youth  without  successful  result, 
who  on  brief  exposure  to  a  mild  case  of  variola  contracted  a  severe 
attack  of  confluent  smallpox.  We  have  also  in  mind  a  young  woman 
wlio  fell  ill  with  hemorrhan;ic  smallpox,  although  she  liad  had  seven 
unavailing  trials  at  vaccination  made  upon  her,  three  of  which  were 
performed  within  a  year  preceding  the  attack  of  smallpox. 

The  late  Mr.  Spurgin,  of  Northampton,  forwarded  some  years  ago 
to  the  Epidemiological  Society  the  particulars  of  a  case  in  which  in 
1825,  a  boy  fourteen  years  old,  whose  family  was  greatly  opposed  to 
vaccination,  was  inoculated  with  variola  six  or  seven  times  without  any 
result,  that  disease  being  then  prevalent.  The  father  then  allowed 
vaccination  to  be  tried,  and  the  boy  was  vaccinated  six  or  seven  times, 
but  equally  without  effect.  About  a  year  after,  when  at  a  distance  from 
home,  he  contracted  natural  smallpox  of  the  discrete  kind,  and  went 
through  the  disease  favorably  (Seaton). 

REVACCINATION. 

Experience  has  demonstrated  the  fact  that  in  a  certain  number  of 
persons  the  protection  from  vaccinia  in  infancy  is  permanent,  while  in 
others  it  gradually  diminishes,  and  after  the  lapse  of  a  number  of  years 
may  become  entirely  extinguished.  The  extinction  of  immunity  is  evi- 
denced by  the  large  number  of  persons  in  adolescent  and  adult  life  who 
are  susceptible  of  revaccination;  also  by  the  observation  that  in  all  epi- 
demics of  smallpox  a  large  proportion  of  the  cases  occur  among  persons 
who  were  vaccinated  in  infantile  life.  The  statistics  of  smallpox  hospitals 
in  this  country  and  in  England  show  that  from  41  to  78  per  cent,  of  the 
admissions  are  postvaccinal  cases.  It  is  very  difficult  to  determine  the 
proportion  of  persons  vaccinated  in  infancy  that  fail  of  permanent  pro- 
tection, but  it  is  beheved  to  be  not  far  from  75  per  cent.  Some  yeais 
ago  a  very  careful  observation  in  a  certain  American  city  showed 
that  of  2362  persons  revaccinated  with  reliable  virus  (no  child  under 
twelve  years  old  with  a  good  scar  being  included  in  this  nimiber)  77.1 
per  cent,  were  susceptible  to  some  form  of  vaccinia. 

We  have  no  means  of  ascertaining  the  age  or  period  of  life  at  which 
the  protection  from  vaccinia  in  infancy  is  liable  to  diminish  or  cease 
entirely,  save  by  applying  the  test  of  revaccination  or  by  noting  at  what 
age  after  primary  vaccination  any  considerable  number  of  persons 
suffer  from  smallpox.  Data  tending  to  demonstrate  the  latter  may  be 
found  in  the  followino-  table: 


46 


VACCINIA 


Cases. 

Deaths 

Percentage 
of  deaths. 

Under  one  year j 

Unvaccinated 

Vaccinated 

Unvaccinated 

Vaccinated  in  infancy,  good  scars 
"           "       "         fair 
"            "       "         poor     " 

Total  number  vaccinated 

Unvaccinated 

Vaccinated  in  infancy,  good  scars 
"           "       "         fair       " 
"         poor      " 

Total  number  vaccinated 

Unvaccinated 

Vaccinated  in  infancy,  good  sears 
"            "       "         fair 
"            "        "         poor 

Total  number  vaccinated 

134 
2 

g6 
0 

64.18 
0.0 

676 

280 

41.42 

One  to  seven  years  .... 

11 
11 
16 

0 
1 
1 

0.0 

9.09 

6.25 

. 

38 

2 

5.26 

320 

61 
24 
64 

87 

2 
2 
9 

27.19 

Seven  to  fourteen  years    .    . 

3.28 
8.33 
14.06 

L 

149 

13 

8.72 

r 

1742 

868 

49.83 

Fourteen  years  and  upward 

1864 
894 
1240 

138 
114 
313 

7.4 
12.75 
25.24 

3998 

565 

14.13 

Among  over  9000  cases  of  smallpox  admitted  to  the  Municipal  Hos- 
pital of  Philadelphia  during  the  past  thirty-four  years  we  have  admitted 
only  two  vaccinated  patients  under  one  year  old.  One  of  these  was  a 
child  eleven  months  old  who  had  been  vaccinated  two  months  pre- 
viously and  showed  a  good  scar.  The  eruption  consisted  of  only  six 
small  vesicles,  and  the  child's  health  was  scarcely  at  all  disturbed.  The 
other  patient  had  the  diseass  so  indistinctly  marked  that  it  was  almost 
impossible  to  feel  certain  of  the  diagnosis  of  varioloid.  An  exceedingly 
modified  form  of  smallpox  was  occasionally  seen  among  well-vaccinated 
children  between  the  ages  of  one  and  seven  years,  but  no  deaths  occurred 
except  where  there  was  a  serious  complication.  The  child  that  died, 
whose  case  is  classified  under  the  head  of  "fair  scars,"  was  a  foundhng 
about  a  year  old,  badly  nourished  and  very  feeble,  with  a  disordered 
digestion.  The  eruption  consisted  of  only  a  very  few  small  vesicles. 
Death  really  resulted  from  inanition.  Very  little  need  be  said  of  the 
cases  classified  in  this  age  period  under  the  head  of  "poor  scars,"  as 
the  vaccination  in  them  had  been  in  good  part  either  imperfect  or 
spurious. 

The  query  is  often  asked,  What  constitutes  a  successful  revaccina- 
tion  ?  This  is  a  question  about  which  there  is  considerable  diversity  of 
opinion.  Many  believe  that,  unless  the  vesicle  and  areola  observe  the 
course  of  true  vaccinia,  the  effect  is  merely  local  and  devoid  of  prophy- 
lactic power.  But  it  is  evident  on  a  little  reflection  that  there  is  no  more 
reason  why  we  should  expect  the  vaccine  disease  produced  by  revac- 
cination  to  be  typical  than  we  should  expect  smallpox  after  vaccination 
to  run  the  typical  course  of  variola  vera.  If  there  be  modified  smallpox 
or  varioloid  after  vaccination,  so  should  there  be  modified  vaccinia  or 


UKVAddlNATION 


47 


vaccinoid.  l^'rom  tlicsc;  premises  the  coiicliision  m;iy  Ix'  (Iciliiccrl  thai 
}is  varioloid  conlors  iitiiniiiiity  a(i;a,iii,sl  a  rcciirrcncc  oF  smallpox,  so  also 
(Iocs  tlic  inodificd  form  ol"  vaccinia,  I'csiilliii^  IVoiri  rcvaccinalioii  rciriove 
froni  the  individiiaJ  whatever  siisccplihilily  U>  the  disease  riiay  he  present. 

It  is  frecjucntly  a  matter  of  ^reut  didiculty  in  revaccinations  to  dis- 
tinfi;uish  between  irritative  local  reactions  and  lesions  which  rcsnit  from 
the  S])ecific  action  of  the  vaccine  princij)le. 

Course  of  Revaccination.  The  <lc<j;ree  of  perfection  of  the  vaccine 
lesion  produced  by  a  revaccination  obviously  dejx'iids  upon  the  extent 
of  vaccinal  susceptibility  remaining  in  the  individual.  W'iiere  the  [pro- 
tection conferred  by  the  primary  vaccination  is  still  complete  no  specific 
result  at  all  is  j)roduced  by  a  second  insertion  of  \'accine  lymph.     Such 


liovaeL-inution  in  an  adult,  showing  vesicles  upon  the  eighth  day. 

a  condition  obtains  in  the  vast  majority  of  children  who  have  been 
vaccinated  in  infancy.  As  time  goes  on  there  occurs  in  most  vaccinated 
individuals  a  gradual  depreciation  in  the  character  of  the  vaccinal  pro- 
tection, and,  pari  passu,  an  increasing  susceptibility  to  revaccination. 
In  some  cases  the  deterioration  of  the  vaccinal  influence  may  go  on 
to  complete  extinction,  in  which  event  the  subject  ofl'ers  an  unmodified 
susceptibility  to  revaccination,  and  a  vaccine  lesion  results  which  is 
almost  or  quite  indistinguishable  from  a  primary  vaccination.  This 
occurs  in  a  comparatively  small  number  of  people,  and  chiefly  in  adults 
whose  primary  vaccination  was  performed  many  years  before.  In  the 
vast  majority  of  persons  the  phenomenon  of  a  typical  vaccinia  can  only 
be  produced  once  in  a  life-time.  IMore  commonly  the  vaccine  lesion  is 
much   modified.     There   may  result   merely  a   papule   or   more   often 


48  VACCINIA 

an  acuminated  vesicle  with  an  irregular  areola  which  runs  a  rather 
rapid  course.  There  is  often  considerable  itching  and  not  infrequently 
marked  constitutional  disturbance.  Severe  systemic  symptoms  appear 
to  develop  more  often  in  re  vaccinations  than  in  primary  vaccinations, 
although  in  many  cases  they  are  absent  altogether. 

Hervieux,  in  1893,  read  before  the  Paris  Academy  of  Medicine  an 
article  on  vaccinoid,  in  which  he  classifies  the  modified  vaccine  lesion 
as  follows:  "There  are  three  types  of  vaccinoid,  dependent  upon  the 
extent  to  which  the  weakening  of  the  immunity  has  advanced: 

"1.  At  the  point  of  inoculation  there  appears  a  pink  papule  hardly 
at  all  elevated  above  the  surrounding  integument,  and  without  any 
areola;  it  disappears  at  the  end  of  a  few  days,  leaving  no  scar. 

"2.  There  forms  an  acuminate  papule,  larger  than  that  seen  in  the 
first  type  of  vaccinoid,  redder,  more  distinctly  visible,  surmounted  by 
a  little  vesicle  at  its  point,  surrounded  by  a  faint  areola,  and  leaving 
after  desiccation  a  little  scab,  which  falls  soon  without  the  formation 
of  a  cicatrix. 

"S.  The  vesicle  is  more  distinct,  the  areola  is  more  pronounced,  the 
scab  is  larger  and  more  adherent,  and  leaves  behind  it  a  cicatrix,  which, 
however,  disappears  in  the  course  of  time.  These  evidences  of  vaccinal 
action  are  usually  accompanied  by  considerable  itching,  but  there  is  no 
fever  and  the  process  confers  immunity." 

Hervieux  states  that  vaccinoid  transmits  by  inoculation  true  vaccinia. 

The  above  classification  does  not  take  cognizance  of  the  well-developed 
vaccine  results  which  we  not  infrequently  encounter  in  individuals  in 
whom  the  immunity  conferred  by  the  primary  vaccination  has  become 
almost  completely  exhausted.  In  these  cases  there  may  be  a  well-formed 
vesicle  with  central  umbilication  surrounded  by  an  areola,  but  the 
course  of  the  disease  is  more  rapid  and  shows  some  degree  of  modifica- 
tion. 

It  is  seen  from  the  above  that  the  vaccinal  result  in  revaccination 
is  most  variable,  and  that  there  is  no  standard  in  an  individual  case. 
The  criteria  upon  which  the  result  in  any  given  instance  might  be 
judged  are  obscured  by  the  indeterminable  degree  of  existing  vaccinal 
susceptibility. 

It  is,  therefore,  often  a  matter  of  difficulty  to  know  whether  the  result 
in  a  revaccination  is  specific  and  genuine,  or  spurious.  Such  doubt, 
however,  should  not  extend  to  the  judgment  of  a  primary  vaccination. 
Jenner's  description  of  the  course  of  vaccinia  constitutes  an  ever-impor- 
tant guide.  Any  result  which  deviates  to  any  considerable  extent  from 
the  description  of  primary  vaccinia  given  by  Jenner  should  not  be 
regarded  as  genuine.  Therefore,  while  the  modified  results  referred 
to  might  be  credited  with  being  the  specific  results  of  revaccination, 
they  should  never  be  regarded  as  genuine  in  primary  vaccinations. 

We  are  convinced  of  the  fact  that  many  local  reactions  similar  to 
those  described  by  Hervieux  are  not  genuine  "takes."  Such  lesions 
not  uncommonly  show  an  unusual  degree  of  inflammatory  action,  even 
as  early  as  the  second  or  third  day.     Upon  this  area  there  frequently 


PLATE   I. 


Secondary  Vaccination  of  Doubtful  Character  (T\velftli  Day) 
foUo^A^ed  by  a  Slightly  Pitted  Scar. 


U  1<:  VA  (JCINA  TfO  N  49 

Sj)rinf^s  up  with  snrj)risinf^  r!i,])i(lity  n.  (norr  or  less  conic;!!  or  }^r|(;l)iil;u- 
blister,  instead  of  a  ty|)ic-al  vcsich;.  This  epidermal  elevation  is  thin- 
roofed,  and  ruptures  readily,  f^ivin<^  exit  to  a  thin,  irritating  fluid,  which 
speedily  dries  in  the  form  of  a  friable,  yellowish  crust,  the  exudation 
eontinuing  to  ooze  out  at  the  margins.  After  shecJding  of  the  crust 
there  is  left  a  faint  scar,  which  is  devoid  of  the  characteristics  of  a  true 
vaccine  cicatrix. 

The  proof  that  many  of  these  results  are  spurious  is  in  the  fact  that 
they  do  not  protect  against  smallpox.  Numerous  cases  have  been 
reported  in  which  lesions  erroneously  interpreted  as  genuine  conferred 
only  a  fancied  and  not  a  real  security  against  smallpox.  Glycerinated 
bovine  lymph  manufactured  by  a  certain  firm  in  1000  was  extensively 
used  in  some  of  the  Southern  States  with  alleged  large  percentage  of 
successes.^  Some  of  the  vaccinated  persons  on  being  exposed  to  small- 
pox a  short  time  afterward  contracted  the  disease.  The  vast  majority 
of  the  persons  upon  whom  this  lymph  had  been  used  were  subsequently 
successfully  vaccinated  with  virus  from  another  source. 

The  following  case  demonstrates  the  difficulty  in  estimating  the 
genuineness  of  revaccination.  In  the  spring  of  1902  a  trained  nurse, 
who  had  been  in  attendance  upon  a  private  patient  suffering  from  small- 
pox, was  brought  into  the  Municipal  Hospital  with  a  mild  attack  of 
varioloid.  She  presented  upon  her  arm  a  poor  mark  from  a  vaccination 
in  childhood.  She  had  been  revaccinated  a  number  of  weeks  before 
admission  with  dried  virus  upon  an  ivory  point.  According  to  her 
description,  a  vesicle  formed  in  from  two  to  four  days.  This  itched 
considerably,  and  later  became  surrounded  with  an  areola  the  size  of  a 
silver  half-dollar.  The  axillary  glands  were  distinctly  tender.  The 
crust  remained  upon  the  sore  for  a  few  weeks.  The  nurse  and  the 
physician  in  attendance  regarded  the  result  as  a  successful  vaccination. 
Upon  admission  to  the  hospital  the  patient  exhibited  a  reddish-brown 
stain  at  the  site  of  vaccination,  but  no  true  scar.  We  were  convinced 
that  the  result  had  been  spurious. 

Value  of  Revaccination. — As  to  the  value  of  revaccination  there  can 
be  no  question.  It  is  the  logical  complement  of  vaccination.  Bousquet 
says  very  truly  that  there  never  has  been  an  epidemic  of  smallpox  since 
the  general  employment  of  Jenner's  discovery  which  has  not  proved  the 
virtue  both  of  vaccination  and  revaccination.  He  adds:  "The  success 
of  revaccination  is  at  the  same  time  the  effect  and  the  proof  of  the  wants 
of  the  system;  ....  when  it  succeeds,  it  not  only  proves  that 
the  protective  power  of  vaccination  is  diminished,  but  it  supplies  a 
remedy  for  this  diminution." 

No  person  should  be  regarded  as  having  been  revaccinated  if  the 
secondary  vaccination  has  not  been  followed  by  a  successful  result. 
Where  a  revaccination,  unproductive  of  result,  is  successful  when  again 
tried  after  a  brief  period  of  time,  the  probabilities  are  that  the  first 
failure  was  due  to  the  emplo}anent  of  inert  lymph  or  imperfect  technique 

1  Reported  by  Dr.  F.  J.  Runyon,  Clarksville,  Tenii. 
•i 


50  VACCINIA 

rather  than  to  insusceptibihty  on  the  part  of  the  subject.  The  failure 
of  a  revaccination  should  not  be  interpreted  as  an  evidence  of  certain 
immunity,  but  the  process  should  be  repeated  with  carefully  selected 
virus  two  or  three  times  in  order  to  eliminate  all  sources  of  error.  When 
the  character  of  the  resulting  lesion  in  a  revaccination  is  doubtful,  the 
procedure  should  be  repeated,  particularly  if  the  individual  is  liable 
to  be  exposed  to  the  infection  of  smallpox. 

Does  insusceptibility  to  revaccination  indicate  Immunity  against  small- 
pox f  Jenner  in  his  "Inquiry"  says:  "Although  the  cowpox  shields  the 
constitution  from  the  smallpox,  and  the  smallpox  proves  a  protection 
against  its  own  future  poison,  yet  it  appears  that  the  human  body  is 
again  and  again  susceptible  of  the  infectious  matter  of  cowpox."  In- 
stances are  given  of  the  cowpox  twice  or  thrice  taken  by  persons  who 
could  not  be  variolated  either  by  inoculation  or  exposure. 

Our  own  experience  would  lead  us  to  believe  that  in  the  great  majority 
of  cases  insusceptibility  to  a  revaccination  carefully  performed  with 
good  lymph  means  insusceptibility  to  smallpox,  and  vice  versa.  The 
English'  Royal  Vaccine  Commission  makes  the  following  conservative 
statement:  "No  doubt  the  want  of  success  (in  a  revaccination)  shows, 
if  the  operation  has  been  thoroughly  performed,  that  the  person  is  at 
the  time  insusceptible  to  the  virus,  and  it  may  be  to  the  virus  of  smallpox 
also." 

Vaccination  After  Smallpox. — In  one  of  his  later  publications  Jen- 
ner remarks:  "Although  the  susceptibility  of  the  virus  of  the  cowpox 
is  for  the  most  part  lost  in  those  who  have  had  the  smallpox,  yet  in 
'  some  constitutions  it  is  only  partially  destroyed,  and  in  others  it  does 
not  appear  to  be  in  the  least  diminished.  By  far  the  greater  number  on 
whom  trials  were  made  resisted  it  entirely ;  yet  I  found  some  on  whose 
arms  the  pustules  from  inoculation  (vaccination)  was  formed  completely, 
but  without  producing  the  common  efflorescent  blush  around  it,  or 
any  constitutional  illness,  while  others  have  had  the  disease  in  the  most 
perfect  manner." 

We  presume  that  Jenner  in  this  essay  refers  to  vaccination  performed 
a  number  of  years  after  an  attack  of  smallpox;  such  results  as  he  observed 
are  quite  in  consonance  with  those  obtained  at  the  present  day.  One 
attack  of  smallpox  will,  in  the  vast  majority  of  instances,  protect  against 
a  second  attack  of  the  disease.  Inasmuch,  however,  as  complete 
immunity  is  not  invariably  conferred  against  smallpox,  it  is  not  to  be 
expected  that  a  permanent  insusceptibility  to  cowpox  will  be  produced. 
f  Therefore  it  is  quite  possible  to  successfully  vaccinate  a  certain  propor- 
tion of  persons  who  have  some  years  before  passed  through  an  attack 
I'  of  variola.  JBjii^inour  experience,  it  is  not  possible  to  produce  a  success- 
ful vaccine  lesion  in  an~individual  who  has  but  recently  been  the  subject^ 
of  smallj^ox.  We  have  repeatedly  tried  to  vaccinate  persons  wKcTirave 
re'cently  reco\eied  from  smallpox,  but  always  without  success,  even 
in  individuals  who  had  never  been  vaccinated. 


VA  cdfNA  />  S(;a  h's  5X 

RETROVACCINATION  OR  VACCINATION   FROM  TKE  HUMAN 
SUBJECT  BACK  TO   THE  BOVINE   SPECIES. 

The  inoculation  of  lyin[)li  from  a  Imiiian  vaccination  into  tin;  cow 
produces  quite  constantly  a  ty})i('al  vaccine  lesion.  'J'his  expedient 
was  at  one  time  resorted  to  with  the  viev^^  of  restoring  j)otency  to  the"" 
attenuated  lymph  of  lonf^"  humanization.  ]\Iost  careful  investij^ators 
concluded,  however,  that  lonr^  humanized  virus  so  transplanted  gained 
neither  in  strength  nor  in  purity,  and,  indeed,  became  more  difficult  to 
retransfer  back  to  the  human  subject,  although  this  (Jifficulty  was 
overcome  in  the  second  human  remove.  Retrovaccination  is  seldom 
employed  at  the  present  day. 

VACCINAL  SCARS. 

Physicians  are  often  in  doubt  as  to  what  constitutes  a  typical  vaccine 
cicatrix.  We  deem  the  subject  of  sufficient  importance  to  warrant  a 
brief  study  of  the  objective  features  of  vaccination  scars. 

When  an  individual  has  undergone  a  vaccinia  which  has  been  per- 
fect in  every  respect,  there  is  left  after  the  fall  of  the  crust  a  cicatrix 
which  is  characteristically  distinctive  in  its  features.  Such  a  scar  is 
indicative  of  the  fact  that  the  bearer  thereof  has  passed  through  the 
vaccine  disease  in  its  most  perfect  form.  The  typical  cicatrix  is  round 
or  oval,  distinctly  excavated,  with  well-defined  margins,  reticulated  or 
foveolated,  and  altogether  presenting  the  appearance  of  having  been 
stamped  into  the  skin  with  a  sharply  cut  die.  Not  all  true  vaccinations 
are  followed  by  scars  presenting  these  characteristics,  but  the  more 
closely  the  cicatrix  approaches  to  this  standard  the  greater  is  the  assur- 
ance that  the  vaccine  disease  has  been  genuine  in  every  respect,  and  is 
calculated  to  give  the  greatest  degree  of  immunity  against  smallpox. 
However,  the  appearance  of  the  scar  may  vary  within  certain  limita- 
tions and  still  be  regarded  as  the  sequential  imprint  of  a  genuine  vac- 
cinia. 

The  variety  of  vaccine  scars  is  very  great;  the  most  frequent  ^•aria- 
tions  from  the  type  above  depicted  are  the  result  of  the  employment 
of  lymph  which  has  become  more  or  less  enfeebled  by  long  human 
transmission.  Modifications  of  the  resulting  scar  may  also  be  due  to 
abnormalities  or  complications  of  the  vaccine  process,  and  to  mechanical 
injury  or  interference  with  the  normal  development  of  the  vesicle. 

In  1851,  Decanteleu,  of  Paris,  published  an  excellent  monograph 
on  the  subject  of  vaccine  scars,  in  which  the  classification  is  given  after 
the  system  of  Lamarck.^  The  author  distinguishes  fifteen  species  of 
vaccine  scars  and  depicts  these  and  many  sub^•arieties  in  .well-executed 
drawings,  some  of  which  are  here  reproduced.  These  drawings  represent 
the  type  of  each  species.  Fig.  10  represents  examples  of  perfect  scars 
resulting  from  vaccinations  with  vigorous  bovine  l^inph  or  of  an  early 

1  Monographic  des  cicatrices  de  la  vaccine,  par  J.  E.  B.  Deuarp-Decanteleu.  Paris,  1S51.    Quoted 
by  Dr.  H.  A.  Martin. 


62  VACCINIA 

human  remove  therefrom.  The  centre  of  the  cicatrix  is  rounded, 
smooth,  and  convex,  and  surrounded  by  a  deep,  depressed,  circular 
furrow  or  sulcus,  which  is  traversed  by  short  ridges  radiating  from  the 
centre  to  the  periphery.  Most  of  these  scars  are  round,  but  occasionally 
those  of  oval  shape  are  encountered.  Decanteleu  found  this  type  of 
scar  in  24  per  cent,  of  over  five  thousand  scars  examined. 

Fig. 10 

J  a  ■■  'I  !  (I 


Ih 


Various  forms  of  good  vaccinal  scars,  showing  a  central,  elevated  disk  surrounded  by  a  furrow 
with  radiating  bands  ;  the  scars  look  as  if  they  had  been'  punched  out  with  a  die.  (Alter  Denarp- 
Decanteleu.) 

Fig.  11 


Smooth  scars  on  a  level  with  the  surrounding  skin,  showing  slight  pitting;  such  scars  may  result 
from  genuine  vaccination  with  long  humanized  virus.    (After  Denarp-Decanteleu.) 

It  is  but  natural  that  vaccine  scars  should  present  variations.  A 
cutaneous  scar,  no  matter  from  what  cause,  is  the  result  of  the  destruc- 
tion of  dermal  tissue.  When  merely  epidermis  is  lost  no  scar  results, 
for  the  cells  of  the  rete  mucosum  proliferate  and  restore  the  complete 
integrity  of  the  cuticle.  When,  however,  a  portion  of  the  cutis  proper 
is  destroyed,  repair  takes  place  through  the  formation  of  fibrous  con- 
nective tissue,  which  is  scar  tissue. 

The  appearance  of  a  cicatrix  will  depend  upon  the  character,  extent, 
and  depth  of  the  tissue  loss,  and  sometimes  upon  certain  personal  pre- 
dispositions. 

The  minute  joveolations  or  'pits  which  are  commonly  seen  in  vaccine 


VA  (JCJ/NA  L  S(!A  ILS  53 

scars,  and  which  are  ref^arded  by  some  as  essci)ti;il  (o  tlif  [x-rfcrt  cifjdrix, 
represent  the  (h'latcd  orifices  of  hair  folhclcs  and  schaccous  ^hirids.  It 
is  readily  seen  that  if  tlie  vaccine  [process  (h-stroys  tlic  si<ir)  to  a  sufficient 
depth  the  hair  folhch'S  and  f^lands  may  he  ohhterated  and  the  resultant 
scar  may  be  devoid  of  the  j)its  referred  to.  It  is  not  at  all  rare  to  see  scars 
from  burns,  ecthyma,  and  perhaps  also  furuncles,  which,  owing  to  the 
presence  of  nmnerous  ])ittinfjjs,  [)resent  an  appearance  wliicli  closely 
simulates  vaccine  cicatrices. 

The  peculiar  foveations  or  large,  excavated  pits  seen  in  the  peripiieral 
portion  of  a  vaccine  scar  probably  result  from  the  specific  histological 
changes  in  the  vaccine  vesicle,  each  excavation  doubtless  representing 
the  floor  of  a  dissepiment  or  cellular  compartment. 

The  greater  the  vigor  and  activity  of  vaccine  lymph,  the  more  inflam- 
matory is  the  process  and  the  deeper  is  the  tissue  destruction.  Animal 
lymph,  which  is  more  vigorous  than  virus  of  long  humanization,  pro- 
duces a  larger  and  deeper-seated  vaccine  lesion  and  consecjuently  a 
larger  and  more  pronounced  scar.  The  cicatrix  following  the  use  of 
long  humanized  virus  is  often  quite  small  and  but  little  depressed 
beneath  the  level  of  the  skin.  The  depth  of  involvement  of  the  true 
skin  appears  to  be  inversely  proportionate  to  the  number  of  human 
removes  from  the  original  cowpox  source. 

Size  of  Vaccine  Scars. — Of  3493  round  scars  examined  byDecanteleu, 
2758,  or  about  75  per  cent.,  had  a  diameter  of  6  to  9  mm.  Sixty-three 
measured  4  mm.,  eleven  measured  20  mm.,  while  the  remainder  had 
intermediate  dimensions. 

With  the  animal  lymph  now  in  use  the  average  diameter  of  the  scar 
is  certainly  greater  than  those  studied  by  Decanteleu.  It  is  not  rare 
to  observe  scars  measuring  half  an  inch  (12  mm.),  three-quarters  of  an 
inch  (18  mm.),  and  even  one  inch  (24  mm.),  and  scars  below  one-third 
of  an  inch  (8  mm.)  are  uncommon. 

We  occasionally  encounter  much  larger  scars  which  are  smooth  and 
glossy  and  devoid  of  foveations,  which  have  evidently  resulted  from 
sloughing  of  the  skin.  While  it  is  quite  possible  that  the  vaccine  process 
in  such  cases  has  conferred  protection,  it  is  impossible,  owing  to  the 
absence  of  the  characteristic  features  of  the  scar,  to  be  sure  that  such 
is  the  case.  A  large  scar,  therefore,  does  not  necessarily  mean  a  good 
scar. 

In  some  individuals,  particularly  negroes,  scar  tissue  tends  to  become 
hypertrophic  and  keloidal  in  character.  It  is  not  uncommon  in  the 
dark  race  to  see  the  vaccinal  scar  smooth  and  elevated  like  a  button, 
instead  of  being  excavated  or  depressed.  This  change  does  not  inter- 
fere with  the  protection  which  the  vaccination  confers,  but  does  obscure 
to  some  extent  the  true  estimate  of  the  perfection  of  the  antecedent  vac- 
cine disease. 

Upon  spontaneous  detachment  of  the  vaccine  crust  the  underlying 
scar  tissue  is  seen  to  be  quite  reddened.  This  is,  of  course,  due  to  the 
hyperR-mia  or  excessive  amount  of  blood  in  the  skin.  In  the  course  of 
some  months  the  color  fades  awav  and  the  scar  tissue  becomes  whiter 


54  VACCINIA 

than  the  surrounding  skin.  While  the  redness  persists  the  scarring  is 
not  so  easily  perceived;  later  it  becomes  more  visible. 

In  the  course  of  many  years,  however,  the  vaccine  scar  often  loses 
some  of  its  distinctness  and  becomes  less  conspicuous.  Indeed,  where 
the  original  scar  has  not  been  pronounced,  it  is  possible  for  it  to  fade 
to  such  an  extent  that  after  a  lapse  of  many  years  it  may  no  longer  be 
visible,  but  disappearance  of  the  scar  is  not  likely  to  result  where  the 
original  vaccinia  has  been  perfect  in  every  respect. 

Scars  After  Revaccination. — ^The  degree  of  perfection  of  a  revac- 
cination  depends,  as  has  been  previously  stated,  on  the  extent  of  vaccinal 
susceptibility  remaining  in  the  individual.  The  more  nearly  the  sec- 
ondary vaccination  resembles  a  primary  vaccinia,  the  more  closely  will 
the  cicatrix  conform  to  the  standard  described  above.  Revaccinations 
are,  in  the  vast  majority  of  instances,  considerably  modified.  They 
produce  what  has  been  aptly  termed  vaccinoid.  This  modified  process 
is  usually  followed  by  a  scar  which  commonly  presents  upon  its  surface 
minute  pittings.  Where  but  little  vaccinal  susceptibility  remains,  and 
the  process  is  greatly  modified,  it  is  quite  possible  that  no  indelible  scar 
will  be  left.  Usually,  however,  a  pitted  scar  marks  the  site  of  a  suc- 
cessful revaccination. 

Discolorations  are  not  infrequently  seen  after  unsuccessful  attempts 
at  vaccination  or  revaccination.  These  are  sometimes  of  a  brownish 
color,  representing  an  increased  deposit  of  pigment;  at  other  times  the 
pigment  is  lost,  leaving  a  white  spot  which  is  neither  elevated  nor  de- 
pressed. Occasionally  the  lines  of  scarification  produced  by  a  pointed 
instrument  will  remain  visible  for  a  long  time,  although  the  vaccination 
has  been  unsuccessful. 

Prognostic  Import  of  Vaccine  Scars. — It  has  been  clearly  shown  that 
the  degree  of  vaccinal  protection  is  proportionate  to  the  perfect  evolu- 
tion of  the  vaccinia.  Marson  and  others  of  large  experience  have  found 
that  smallpox  is  less  fatal  among  patients  who  bear  unmistakable 
evidence,  in  the  form  of  typical  scars,  that  the  vaccine  disease  has  run 
a  perfect  course.  While  Jenner  never  said  very  much  about  the  char- 
acter of  the  scar,  he  nevertheless  constantly  insisted  that  the  vaccinal 
process  should  observe  a  certain  definite  course  in  order  that  the  pro- 
tection should  be  perfect. 

In  examining  the  vaccine  cicatrices  of  a  large  number  of  persons,  it 
is  found  that  the  scars  differ  considerably  in  appearance  and  degree  of 
perfection;  the  question  arises,  Can  protection  be  measured  to  any 
degree  by  the  different  characteristics  of  the  scars?  There  is  no  doubt 
that  many  persons  with  quite  inferior  vaccine  marks  are  fairly  well 
protected,  or  even  enjoy  immunity  against  smallpox,  while  some  with 
typical  marks  prove  to  be  susceptible  to  the  disease,  and  indeed  some- 
times perish  from  it.  But  such  results  must  be  regarded  as  exceptions 
to  the  rule.  When  a  large  number  of  patients  are  examined  and  the 
results  tabulated,  the  degree  of  protection  is  found  to  bear  a  very  close 
and  direct  relation  to  the  character  of  the  vaccine  cicatrices. 

All  of  the  patients  represented  in  the  subjoined  tables  were  carefully 


VA(.'(J/iyAlj  SdMlS  Ofj 

examined  on  their  admission  to  tlic  hospital,  and  the  number  and  char- 
acter of  their  varciiK;  scars  at  once  rec;orded.  At  this  time  it  was,  of 
course,  inij)ossihh'  to  foi-etcll  the  final  outcome  of  the  disease.  The 
scars  are  divided,  according;  to  their  rpiality,  into  three  grades,  which 
are  designated  in  the  tables  by  the  terms  (jood,  fair,  and  poor.  Under  the 
first  head  are  included  all  cases  presenting  typical  vaccine  cicatrices — 
that  is  to  say,  cicatrices  which  are  distinctly  excavated,  with  well-defined 
margins,  reticulated  or  foveolated,  and  altogether  presenting  the  a})pear- 
ance  of  having  been  stamped  into  the  skin  by  a  sharply  cut  die.  Under 
the  second  head  are  included  all  cases  with  scars  Iiaving  the  same  general 
characteristics,  though  much  less  distinctly  marked.  Under  the  third 
head  have  been  classified  all  cases  having  scars  which  were  said  to  have 
been  the  result  of  vaccination,  but  which  in  very  many  instances  were 
so  indistinct  or  uncharacteristic  as  to  make  it  difficult  and  sometimes 
impossible  to  recognize  them  as  vaccine  scars. 

In  the  cases  classified  under  the  heads  of  both  good  and  fair  marks 
the  patients  had  all,  doubtless,  passed  through  a  well-marked  or  reason- 
ably well-marked  course  of  vaccinia  in  infancy.  We  are  strongly  of  the 
opinion  that  very  many  of  the  cases  classified  under  the  head  of  "poor 
cicatrices"  were  never  successfully  vaccinated.  Very  often  we  felt 
fully  convinced  at  the  time  of  making  the  examination  and  recording 
the  vaccine  condition  that  such  was  the  case,  but,  as  the  patients  insisted 
that  they  had  been  vaccinated,  we  could  not  reject  their  testimony 
without  being  considered,  especially  by  the  enemies  of  vaccination, 
partial  judges.  It  certainly  does  not  detract  from  the  reputation  of 
vaccination  to  know  that  when  the  vaccine  process  is  irregular,  imper- 
fect, or  spurious,  the  protection  is  diminished  or  absent.  As  the  mean 
death  rate  of  the  cases  showing  good  and  fair  cicatrices  is  8.34,  and  the 
death  rate  of  those  showing  poor  scars  is  22.64,  it  is  evident  that  not  only 
very  many  of  the  latter  had  been  imperfectly  vaccinated,  but  that  a 
large  number  had  never  been  subjected  at  all  to  the  vaccine  influence. 

As  tending  to  show  that  the  degree  of  protection  can  be  measured  to 
a  considerable  extent  by  the  quality  of  the  vaccine  scars  borne  by  per- 
sons, the  following  table  of  cases  of  smallpox  treated  at  the  Municipal 
Hospital  is  presented: 


Vaccinated  in  infancy,  good  scars 
"  "       "         fair       " 

"  "        "  poor 

Postvaccinal  cases 
Unvaccinated    "  ... 

Total 


Cases. 

Deaths. 

2335 
1105 
1524 

152 
135 
345 

4964 
3687 

632 
1542 

8651 

2174 

Percentages 
of  deaths. 


6.5 
12.21 
22.64 


12.53 

41.82 


25.13 


The  opinion  has  been  advanced,  more  especially  by  jNIarson  and 
other  English  writers,  that  the  degree  of  vaccinal  protection  in  an  indi- 
vidual is  directly  proportionate  to  the  number  of  insertions  made. 


56 


VACCINIA 


Marson  based  this  opinion  upon  an  extended  experience  with  small- 
pox, in  which  he  found  that  the  disease  was  less  severe  and  less  fatal  in 
proportion  to  the  number  of  vaccine  scars  that  the  patient  presented. 

The  following  table  published  by  Marson  gives  an  analysis  of  all  the 
cases  of  smallpox  admitted  into  the  London  Smallpox  Hospital  between 
the  years  1836  and  1855: 


Patients  admitted  with  smallpox. 

Number 

of 
patients. 

Character 
of  scar. 

Cases. 

Died. 

Rate  %  of  mortality 

from  smallpox  after 

deducting  deaths 

from  superadded 

diseases. 

1.  Having  one  vaccine  scar     .    . 

2.  Having  two  vaccine  scars     .    . 

3.  Having  thiree  vaccine  scars  .    . 

4.  Having  four  or  more  vaccine 

scars. 

5.  Stated  to  have  been  vaccinated, 

2001     j 

1446     1 

518     -j 

544     1 
370 

17 

Good 
Indifferent 

Good 
Indifferent 

Good 
Indifferent 

Good 
Indifferent 

1032 
969 

873 
573 

307 
211 

358 
186 

370 
17 

54 
134 

32 

57 

7 
9 

2 
3 

101 
3 

402 

23.57 

but  having  no  scar. 
6     stated  to  have  been  vaccinated, 

6.60 

but  particulars  of  cicatrix  not 
noted. 

Total 

4896 

6.56 

In  addition  to  Marson's  statistics  the  English  Vaccination  Commis- 
sion presents  observations  on  6839  other  cases.  The  figures  are  as 
follows : 


Scars. 

1  scar 1357 

2  scars 1971 

3  scars '.  1997 

4  scars 1514 


Deaths. 

Percentages 

85 

6.2 

115 

5.8 

75 

3.7 

34 

2.2 

In  summing  up,  the  Commission  says:  "The  evidence  appears  to  point 
to  the  conclusion  that  the  greater  the  number  of  marks  the  greater  is 
the  protection  enjoyed  by  the  vaccinated  person  in  relation  to  smallpox. 
This  further  indication  also  seems  to  be  afforded,  that  while  the  dura- 
tion in  this  respect  between  those  with  one  and  those  with  two  marks 
is  not  very  great,  there  is  a  very  marked  contrast  between  those  with 
four  or  even  with  three  marks  as  compared  with  those  with  either  one 
or  two." 

Our  own  experience  on  the  comparative  protection  conferred  by 
multiple  scars  does  not  entirely  coincide  with  that  of  the  English  writers, 
as  will  be  seen  on  reference  to  the  following  tp,ble: 


VA  C'flTNA  L  SdA  ns 


57 


Cabics  of  SMAr.r.pox  TiiEATico  IN  THE  Philadelphia  MuNKJirAi.  II(j.si'Ital 

FKOM    1871   TO    1003,  JNC'LUHIVK. 

Number  of  vaccine  scans  and  death  rate. 


Cases. 

Death  H. 

PercentaRes 
of  deaths. 

Unvaecinated 

Claiming  to  have  been  vaccinated  ;  no  visible  scar 
Vaccinated  seven  days  or  less  before;  variolous  eruption 

"         longer  than  seven  days  before  variolous  eruption 

Vaccinated  in  infancy,  one  good  scar 

"          "       "           "    fair      " 

"          "        "           "    poor    " 

3220 

.   258 
106 
264 

1282 
695 
1176 

1392 
150 
39 
39 

84 
90 
293 

467 

28 
19 
30 

43.23 
.58. 13 
38.79 
14.77 

6. 55 
14.39 
24.83 

Total  ninnber  showing  one  scar  .... 

3153 

14.81 

Vaccinated  in  infancy,  two  good  scars      .     ■  . 

"          "       "          "    fair       " 

"          "       "           "    poor      " 

486 
182 
153 

5.76 
10.44 
19.61 

Total  number  showing  two  scars 

821 

183 
65 
72 

77 

9.50 

Vaccinated  in  infancy,  three  good  scars 

"          "        "            "     fair       " 

"         "       "            "     poor      " 

11 

4 
14 

29 

6.01 
6.15 
19.44 

320 

9.06 

Vaccinated  in  infancy,  four  or  more  good  scars 

"          "       "           "     "      "      fair      "          ... 
"         "       "           "     "      "      poor     "          ... 

291 

95 

105 

25 
11 
12 

8.68 
11.57 
11.42 

Total  number  showing  four  or  more  scars . 

491                    48 

9.77 

We  believe  that  the  quality  of  vaccine  scars  is  a  far  more  rehable 
index  of  the  degree  of  protection  than  the  quantity.  The  table  shows 
that  when  the  scars  are  typical  it  makes  but  little  difference  whether 
they  are  single  or  multiple,  the  protection  being  almost  the  same.  There 
is  no  doubt  that  vaccinia  characterized  by  a  single  typical  vesicle  confers 
immunity  against  smallpox;  it  is  impossible  for  multiple  vesicles  to  do 
more.  We  have  seen  some  adults  with  smallpox  who  bore  upon  their 
arms  as  many  as  twenty  scars  from  an  infantile  vaccination;  they  appeared 
to  be  no  better  protected  than  individuals  with  one  scar  of  equal  Cjuality. 

We  have  seen  a  girl  of  twelve  years  who  had  six  vaccination  scars 
from  infancy  contract  smallpox;  the  six  insertions  did  not  seem  to  confer 
greater  protection  than  one  ordinarily  does. 

However,  as  a  safeguard  against  failure  when  the  danger  of  variolous 
infection  is  imminent,  it  is  advisable  in  vaccinating  to  make  more  than 
one  insertion. 

The  English  Vaccine  Commission  report  indicates  that  patients  with 
foveated  scars  enjoy  an  advantage,  both  as  far  as  the  fatality  and  the 
mildness  of  the  disease  are  concerned,  over  those  with  unfoveated 
scars.  The  data  upon  which  this  conclusion  is  based  are,  however, 
too  limited  to  warrant  any  too  great  importance  being  laid  upon  this 
point.  Furthermore,  in  the  statistics  of  some  outbreaks  the  figures  were 
by  no  means  conclusively  in  favor  of  the  foveated  class. 


58  VACCINIA 

There  was  some  evidence  to  support  the  view  that  there  was  superior 
protection  according  as  the  area  of  the  vaccination  marks  was  larger. 

VACCINAL  COMPLICATIONS  AND  INJURIES. 

The  chapter  on  vaccination  statistics  will  indicate  the  great  life-saving 
power  of  vaccination.  During  the  past  century  there  have  been  probably 
more  than  fifty  million  human  lives  preserved  through  its  beneficent 
influence.  If  accidents  have  now  and  then  attended  the  practice  of 
vaccination  and  deaths  have  resulted  therefrom,  deplorable  though 
these  results  may  be,  they  fade  into  insignificance  when  compared  with 
the  inestimable  benefits  conferred  by  this  procedure. 

In  discussing  the  complications  and  accidents  of  vaccination  we  have 
tried  to  preserve  a  fair  judicial  attitude.  We  present  the  entire  list  of 
injuries  that  have  been  claimed  from  time  to  time  to  result  from  vac- 
cination. The  list  is  a  long  and  formidable  one  and  calculated  to  con- 
vey the  impression  to  the  mind  of  the  inexperienced  that  vaccination  is 
a  dangerous  procedure.  We  desire  to  point  out  the  fact  that  many  of 
the  enumerated  conditions  are  excessively  rare,  and  that  others  are  not 
the  result  of  vaccination  at  all,  but  are  inserted  in  order  to  be  fairly 
discussed. 

Vaccinal  Mortality. — ^The  practice  of  vaccination  is  a  measure  which 
is  not  absolutely  unattended  with  risk.  It  must  be  remembered  that 
vaccinia  is  an  infectious  disease,  and  that  some  danger  attaches  to  the 
mildest  diseases  of  this  character.  Furthermore,  vaccinia  is  compli- 
cated by  the  presence  of  a  wound,  and  cutaneous  wounds,  particularly 
if  neglected,  are  liable  to  infection  with  disease-producing  germs.  Even 
a  pin  scratch  has  on  more  than  one  occasion  given  opportunity  for  an 
infection  which  has  resulted  in  death. 

Most  of  the  injuries  and  fatalities  that  from  time  to  time  result  from 
vaccination  are  preventable.  Already  the  use  of  bovine  lymph,  special 
methods  of  preparation  and  preservation,  an  improved  vaccination 
technique,  and  care  of  the  vaccinated  arm  have  taught  us  how  to  avoid 
most  of  the  vaccinal  complications. 

Deaths  have  from  time  to  time  resulted  from  vaccination,  but  the 
number  is  exceedingly  small  when  compared  with  the  enormous  num- 
ber of  vaccinations  performed. 

In  England,  where  antivaccination  prejudice  is  strongest,  the  alleged 
death  rate  is  the  highest.  According  to  the  Registrar  General's  return 
from  1881  to  1889  the  number  of  deaths  certified  as  connected  with 
vaccination  was  476,  or  about  53  a  year.  Inasmuch  as  6,739,902  pri- 
mary vaccinations  were  performed  during  this  period  of  nine  years, 
we  have  an  average  death  rate  of  1  to  14,159  primary  vaccinations. 
Admitting  that  vaccination  was  really  accountable  for  all  of  these 
deaths,  the  mortality  rate  is,  as  Acland  has  pointed  out,  still  far  below 
that  attendant  upon  the  use  of  chloroform  as  an  anaesthetic.^ 

1  The  deaths  from  chloroform  in  England  are  about  1  in  every  2000  ansesthesias  ;  from  ether,  1  in 
20,000. 


VAC(JINAL  aoMI'LK'ATIONS  AND  IS.imiKS  '/.) 

The  mortality  of  vaccination  in  Germany  carefully  estimated  by 
Voigt"^  is  stated  to  have  heen  35  in  2,275,000  vaccinations  fa  ratio  of  ] 
death  to  65,000  vaccinations),  including  both  primary  and  secondary 
insertions.  Of  the  deaths,  19  were  due  to  erysipelas,  8  to  gangrene,  2 
io  cellulitis,  3  to  "blood  poisoning,"  and  3  to  other  causes. 

Voigt  himself  during  an  ex})ciicnce  of  twenty  years  vaccinated  over 
a  quarter  of  million  of  people.  Within  the  last  five  years  he  has  vac- 
cinated 100,000  people  with  but  a  single  death.  This  is  an  evidence 
of  the  results  that  may  be  expected  when  all  precautions  are  taken. 

Kiibler^  states  that  in  the  thirteen  years  from  18^5  to  1897  there  were 
recorded  113  deaths  among  32,000,000  vaccinations  in  the  German 
Empire;  46  of  these  deaths  were  shown  to  have  been  caused  by  subse- 
quent wound  infection  through  some  neglect  on  the  part  of  the  patient. 
In  only  67  cases  was  there  a  connection  with  the  vaccination  itself;  even 
in  these  cases  the  relation  was  not  proved,  but  it  could  not  be  disproved. 
Admitting  that  all  of  the  113  deaths  resulted  from  vaccination,  this 
would  give  a  rate  of  1  death  in  every  283,177  vaccinations. 

When  this  mortality  is  compared  with  the  hideous  loss  of  life  from 
smallpox  in  the  prevaccination  days,  and  when  it  is  recognized  that 
properly  repeated  vaccination  is  an  absolute  safeguard  against  small- 
pox, the  virtues  of  this  procedure  can  be  properly  appreciated. 

It  is  a  judicial  weakness  of  human  judgment  to  confound  sequence 
and  consequence;  and  the  medical  mind  even  in  matters  medical  is  not 
exempt  from  this  failing.  It  is  scarcely  to  be  wondered  at,  therefore, 
that  laymen  with  but  a  hazy  comprehension  of  medical  theory  and 
practice  should  view  a  succession  of  events  in  the  light  of  cause  and 
effect.  It  would  be  a  difficult  matter  to  prove  to  the  average  individual 
that  a  cutaneous  disease  appearing  within  a  few  days  after  the  perform- 
ance of  a  vaccination  was  not  the  result  of  it. 

Vaccination  is  more  universally  practised  throughout  the  entire 
world  than  any  other  medical  procedure.  Probably  three-quarters  of 
all  civilized  people  submit  to  the  inoculation  of  vaccine  material  in 
order  to  be  granted  immunity  against  smallpox.  In  Germany  alone, 
from  1885  to  1897,  32,000,000  people  were  vaccinated. 

In  the  natural  course  of  events  it  must  occur  that  among  millions  of 
people  there  will  be  some  in  whom  the  vaccination  will  have  just  pre- 
ceded the  development  of  some  disease  or  other.  I>,aymen  and  even 
physicians  are  too  prone  under  such  circumstances  to  apply  the  prin- 
ciple of  post  hoc  ergo  propter  hoc.  Vaccination  immunizes  only  against 
smallpox;  it  will  not  protect  one  from  tuberculosis,  syphilis,  skin  dis- 
eases, etc.  Therefore,  as  these  are  common  diseases,  it  will  of  necessity 
happen  that  they  will  from  time  to  time  attack  persons  who  have  been 
recently  vaccinated.  We  do  not  desire  to  convey  the  impression  that 
vaccination  never  does  any  harm,  but  we  are  convinced  that  many  mor- 
bid conditions  are  attributed  to  vaccination  which  bear  no  relation  to  it 
save  a  chronological  one. 

1  Quoted  by  Holt,  Diseases  of  Children.  -  History  of  Smallpox  and  Vacciiiation,  1901. 


60 


VACCINIA 


Vaccination  and  Cutaneous  Disease. — The  following  classification 
of  skin  diseases  associated  with  vaccination  is  a  modification  of  that 
formnlated  by  Malcolm  Morris  and  later  revised  by  Frank: 


Local . 


{ 


Eruptions  attributable  to  , 
the  vaccine  virus  pure  j 
and  simple. 


t  Constitutional 


II.  Eruptions  attributable  to 
mixed  infection  at  time 
of  vaccination  or  later. 


Local . 


Constitutional 


Normal  vaccinia. 

Erythematous  dermatitis  (areola). 

Generalized  vaccinia. 
Diffuse  vaccine  erythema. 
Vaccinal  roseola . 
Vaccinal  lichen. 
Vaccinal  miliaria. 
Purpura. 

Erythema  multiforme. 
Urticaria. 

{Erysipelas. 
Impetigo  contagiosa. 
Furunculosis. 
Vaccinal  ulcer. 
Localized  gangrene. 
L  Cellulitis. 

f  Disseminated  gangrene. 
Syphilis. 
Leprosy  (?). 
Tuberculosis  (?). 


III.  Eruptions   sometimes  fol- 
lowing vaccination. 


f  Eczema. 

I  Bullous  eruptions  (acute  pemphigus,  dermatitis  bullosa, 

j         dermatitis  herpetiformis). 

1  Psoriasis. 

I  Furunculosis. 

i  Urticaria. 


The  above  classification  is  doubtless  faulty  in  many  respects  and 
open  to  criticism,  but  will  perhaps  serve  the  purpose  of  indicating  in  a 
general  way  the  etiological  factors  in  the  production  of  the  various  der- 
matoses that  may  complicate  vaccinia. 

Generalized  Vaccinia. — This  is  perhaps  the  only  eruption  among  those 
enumerated  (with  the  exception,  of  course,  of  the  normal  vaccine  dis- 
ease) which  may  with  positiveness  be  attributed  to  the  pure  vaccine 
virus.  There  are  two  varieties  of  generalized  vaccinia — 1.  Spontaneous 
generalized  vaccinia  (vaccinal  eruptive  fever,  vaccinola).  2.  General- 
ized vaccinia  from  autoinoculation. 

Spontaneous  generalized  vaccinia  is  an  extremely  rare  condition; 
many  cases  formerly  regarded  as  instances  of  spontaneous  diffusion 
of  the  eruption  are  in  all  likelihood  cases  of  autoinoculated  vaccinia. 
The  eruption  appears  usually  from  the  fourth  to  the  tenth  day  after 
vaccination  and  most  often  from  the  sixth  to  the  ninth  day. 

The  lesions  appear  in  successive  crops  and  pass  through  the  stages 
of  papule,  vesicle,  and  pustule.  The  eruptive  lesions,  being  of  different 
age,  may  be  seen  in  varying  stages  of  development.  Complete  subsi- 
dence of  the  efflorescence  usually  occurs  before  the  twenty-first  day. 
The  lesions  may  be  few  or  numerous  and  may  appear  upon  any  portion 
of  the  body  surface.  Fever  is  absent  in  some  cases  and  present  in  others, 
being  usually  proportionate  to  the  extent  of  the  eruption  and  the  asso- 
ciated  complications,   particularly  glandular  enlargement. 

The  causes  of  generalized  vaccinia  are  but  poorly  understood.  An  ab- 
normal susceptibility  to  the  vaccine  virus  has  been  invoked  as  a  cause. 
The  administration  of  the  vaccine  material  through  the  digestive,  cir- 
culatory, or  respiratory  system  is  regarded  by  Acland  as  capable  of 


VACCINA  1.  COMPIJdArrONS  AND  fNJfl/if/'JS  fj] 

iiuluciiij^  ii  j^ciKTiiliziitioii  of  llic  cnipdc))!.  This  wrilcr  niciilion-,  ;iii 
observation  of  Etieiine  tfiut  a  ^(Micralized  vaccinal  crii})tion  had  been 
|)ro(liice(l  in  children  who  had  sucked  their  vaccination  pocks;  general- 
ized vaccinia  has  also  been  produced  by  the  intentional  feedinj^  of  pow- 
dered vaccine  crusts  to  subjects  |)reviously  rej^arded  as  insusceptible 
to  vaccinia. 

Chauveau  was  able  to  produce  a  generalized  eruption  in  horses  by 
subcutaneous  injection  of  vaccine  lymph  and  also  by  administration 
through  the  res])irat()ry  and  digestive  tracts. 

Generalized  vaccinia  may  present  a  considerable  resemblanr-e  to 
variola.  It  may  usually  be  distinguished  by  the  absence  of  an  initial 
stage,  its  occurrence  after  vaccination,  the  appearance  of  the  eruption 
in  crops,  and  the  irregular  distribution  of  the  lesions.  Its  differentiation 
from  inoculated  variola  is  rather  more  difficult. 

Generalized  Vaccinia  from  Autoinoculation. — This  foim  of  generaliza- 
tion of  the  vaccine  lesions  is  by  no  means  rare.  Many  writers  at  the 
present  day  are  inclined  to  regard  the  vast  majority  of  cases  of  general- 
ized vaccinia  as  due  to  external  inoculation.  French  writers  have 
reported  a  number  of  instances  of  diffusion  of  the  vaccinal  eruption 
over  an  extensive  cutaneous  area  the  seat  of  a  moist  eczema.  Unless 
there  is  danger  of  exposure  to  smallpox,  it  is,  indeed,  advisable  to  post- 
pone vaccination  if  the  subject  is  suffering  from  a  dermatosis  in  which 
there  is  denudation  of  the  skin.  The  number  of  lesions  may  be  but  two 
or  three  or  there  may  be  a  profuse  eruption.  The  development  of  a 
few  supermnnerary  lesions  in  the  neighborhood  of  the  original  vaccine 
insertion  is  by  no  means  uncommon;  this  may  occur  even  when  there 
is  no  demonstrable  abrasion  of  the  skin.  The  virus  may  be  transferred 
by  the  patient  himself  through  scratching,  or  it  may  be  conveyed  by  a 
second  person.  Fig.  12  represents  six  vaccine  lesions  upon  the  face  of 
a  woman  which  were  produced  by  the  finger-nails  of  an  infant  in  arms; 
both  the  mother  and  child  had  been  vaccinated  upon  the  arm.  We 
recall  the  case  of  an  infant  born  of  a  variolous  mother  at  seven  and  a 
half  months.  The  child  was  immediately  vaccinated,  the  insertions 
"taking:"  well.  From  eleven  to  fourteen  davs  after  the  vaccina- 
tion,  lesions  indistinguishable  from  vaccine  vesicles  appeared  upon 
the  left  side  of  the  thigh,  the  left  loin,  the  middle  of  the  back,  the 
hip,  the  splenic  region,  and  the  scrotum.  These  varied  in  diam- 
eter from  five-eighths  of  an  inch  to  three-quarters  of  an  inch,  were 
depressed  in  the  centre,  the  depression  later  acquiring  brownish  crusts. 
Sixteen  days  after  the  vaccination  a  half-doxen  firm  variolous  papules 
developed  upon  the  face,  neck,  scalp,  and  foot.  The  infant  was  feeble 
and  died  a  few^  days  later.  In  this  case  it  w^as  difficult  to  determine 
whether  the  multiplicity  of  vaccine  lesions  was  due  to  circulatory  diffu- 
sion or  autoinoculation.  Accidental  vaccine  lesions  may  appear  upon 
any  portion  of  the  cutaneous  or  mucous  surfaces.  They  may  even  occur 
upon  the  conjunctiva  or  upon  the  eyeball.  In  the  latter  case  there  may 
be  loss  of  vision.  One  of  the  writers  recently  saw  in  the  practice  of  a 
medical  friend,  an  ophthalmologist,  a  case  in  which  a  vaccine  lesion 


62 


VACCINIA 


had  been  accidentally  produced  upon  the  bulbar  conjunctiva.  The 
family  physician  while  vaccinating  several  children  was  requested  by 
the  mother  to  remove  a  foreign  body  from  her  eye.  The  physician, 
without  cleansing  his  hands,  everted  the  eyelids  to  determine  the  pres- 
ence of  the  offending  substance.  In  the  due  course  of  time  a  vaccine 
vesicle  appeared,  accompanied  by  tremendous  chemosis;  the  eye  was 
saved  only  after  prolonged  skilful  treatment. 

The  lesions  in  vaccinia  generalized  by  autoinoculation  appear  at 
intervals  after  the  original  vesicle  is  well  advanced;  they  seldom  con- 
tinue to  make  their  appearance  after  the  third  week. 


Fig.  12 


Accidental,  multiple  vaccinations  produced  by  the  scratching  of  an  infant's  hand 
contaminated  from  a  vaccine  lesion  on  its  own  arm. 


Sore  Arm. — Under  this  caption  we  shall  discuss  a  condition  which 
only  in  its  severer  phases  is  to  be  regarded  as  a  complication.  A  certain 
amount  of  inflammatory  reaction  (areola)  about  the  fully  developed 
vesicle  is  to  be  viewed  as  a  not  undesirable  and  probably  an  essential 
part  of  the  normal  evolution  of  the  vaccine  lesion.  It  not  infrequently 
happens  that  instead  of  a  moderate  erythema  and  oedema  of  the  skin, 
these  phenomena  are  present  to  an  excessive  degree.  Now  and  then 
the  inflammation  about  a  vaccination  reaches  a  violent  degree  of  inten- 
sity and  spreads  over  a  considerable  portion  or  the  whole  of  the  affected 
arm.     In  such  cases  the  cellular  tissue  may  become  implicated,  giving 


VA(/('fNy\fj  COMI'lJdATIONH  AND   / N.KU!/ i:S 


C/.i 


rise  to  a  difl'iise  cdluliiis.  Tlie  Jirin  uruJer  such  coixliiicjiis  is  i'(;fl,  swfjllcn, 
hot,  and  painful,  and  there  is  apt  to  be  some  associated  systemic  dis- 
turbance. 

In  other  cases  the  inflammation  is  more  circumscribed  and  its  force 
is  spent  upon  the  vaccine  lesion  and  the  skin  in  its  imni(;diatc  ncifrhbor- 
hood.  In  such  cases  a  necrosis  of  the  cutaneous  and  suljcutaneous 
tissues  may  occur,  with  the  formation  of  a  slouch.  Wlien  this  is  thrown 
off  an  ulcer  is  left  at  the  site  of  vaccination.  In  other  cases  the  vaccinia 
may  pursue  a  normal  course  to  the  development  and  decline  of  the 
areola,  but  instead  of  the  formation  of  a  typical  scab  an  excavated 
ulcer  appears,  covered  by  a  soft,  thin  crust,  which  fre(|uently  falls  off 
and  is  renewed,  the  idcer  persisting  in  this  manner  for  a  lont^  time.  Mar- 
Fro,  i:'. 


Sloughing  at  the  vacciuation  site  accompanying  au  unusually  inflammatory  vaccination. 

tin,  of  Boston,  repeatedly  observed  this  irregular  course  upon  arms 
which  had  been  vaccinated  with  long  humanized  virus,  whereas  upon 
the  opposite  arm  on  which  bovine  virus  had  been  simultaneously  em- 
ployed a  perfect  result  was  obtained. 

This  observation,  as  well  as  the  scientific  investigations  of  later-day 
observers,  suggests  that  the  excessively  "sore  arm"  is  due  to  the  intro- 
duction of  something  in  addition  to  the  pure  vaccine  \urus,  and,  further- 
more, that  this  additional  something  is  of  the  nature  of  extraneous 
micro-organisms.  The  Lancet  Special  Commission  on  Glycerinated 
liymph^  says  that  "the  presence  of  a  large  number  of  organisms  in  an 


1  London  Lancet,  1902 


64  VACCINIA 

active  vaccine  lymph  renders  the  local  lesion  more  severe,"  and  that 
"many  of  the  bad  results  obtained  in  vaccination  are  due  to  imperfect 
sterilization  of  the  skin  and  want  of  protection  against  the  invasion  of 
the  weakened  and  abraded  tissues  by  extraneous  organisms."  It  is 
also  stated  that  "one  of  the  most  certain  methods  of  producing  severe 
oedema  is  for  the  patient  to  use  his  arm  freely  and  to  bring  about  per- 
spiration just  before  and  after  the  vesicles  have  begun  to  form." 

Tt  is  not  uncommon  for  the  arm  to  become  very  "sore"  as  the  result 
of  thoughtless  or  accidental  traumatism  on  the  part  of  the  vaccinee. 
The  vesicle  is  frequently  ruptured  by  a  blow,  friction  of  clothing,  scratch- 
ing, and  other  like  causes.  Where  the  vesicle  is  unprotected  the  shirt- 
sleeve often  becomes  glued  to  the  vaccination  lesion,  and  attempts  at 
separation  cause  a  detachment  of  the  crust.  All  of  these  forms  of  trau- 
matism doubtless  act  in  the  same  manner;  they  prevent  the  formation 
of  a  firm,  compact  crust  which  is  nature's  protective  covering  of  the 
vaccine  wound.  By  opening  up  the  wound  they  permit  of  infection 
with  extraneous  germs  which  may  produce  merely  excessive  inflamma- 
tion or  may  lead  to  ulceration  or  other  more  severe  vaccinal  complications. 

Inasmuch  as  we  can  obtain  a  lymph  which  is  rendered  free  of  extra- 
neous germs  by  the  process  of  glycerinization,  by  proper  care  of  the  arm 
before,  during,  and  after  vaccination,  we  should  be  able,  in  the  vast 
majority  of  instances,  to  prevent  the  development  of  "sore  arms." 

Vaccinia  Hemorrhagica. — From  time  to  time  cases  of  vaccinia  are 
seen  in  which  the  areola  about  the  vesicle  at  the  acme  of  its  development 
becomes  hemorrhagic,  assuming  the  appearance  of  a  diffuse  ecchyraosis. 
In  some  instances  the  skin  beyond  the  areola  may  present  a  bluish 
appearance.  In  rare  cases  there  may  occur  scattered  petechise  and 
ecchymosis  and  hemorrhages  from  some  of  the  mucous  membranes. 
The  cause  of  this  complication  is  obscure;  it  is  doubtless  not  so  much 
due  to  any  peculiarity  of  the  lymph  as  to  some  underlying  systemic 
condition  favoring  hemorrhagic  extravasation,  such  as  scorbutus. 

Vaccinal  Ulceration. — Ulceration  at  the  site  of  insertion  of  the  lymph 
is  by  no  means  an  uncommon  complication  of  vaccinia.  Acland'  says 
that  nearly  4  per  cent,  of  the  vaccinal  injuries  inquired  into  by  the 
English  Local  Government  Board  (1888-91)  were  due  either  to  ulcera- 
tion or  glandular  abscess.  There  is  in  all  probability  one  of  two  factors 
which  may  give  rise  to  vaccinal  ulceration — either  the  introduction  into 
the  skin  of  extraneous  micro-organisms  (at  the  time  of  vaccination  or 
later)  capable  of  producing  a  tissue  necrosis,  or  an  abnormal  or  vitiated 
state  of  health  which  permits  of  an  excessive  and  unusual  local  reaction. 
Both  of  these  factors  appeared  to  play  an  important  role  in  the  produc- 
tion of  "bad  arms"  among  the  soldiers  during  the  United  States  Civil 
War.  In  the  admirable  report  of  the  Board  of  Health  of  Louisiana  of 
1884,  compiled  by  Dr.  Joseph  Jones,  we  read  the  following:  "In  scor- 
butic patients  all  injuries  tended  to  form  ulcers  of  an  unhealthy  charac- 
ter, and  the  vaccine  vesicles,  even  when  they  appeared  at  the  proper  time 
and  manifested  many  of  the  usual  symptoms  of  the  vaccine  disease, 

1  Article  on  Vaccinia,  Allbutt's  System  of  Medicine,  p.  59G. 


VA(J(JINAIj  (JOMriJdATIONS  and  INJlfltll'lS  65 

were  nevertheless  larger  and  more  slow  in  licalin^r,  und  tlic  srahs  [jrc- 
sented  an  enlarged,  scaly,  dark,  unhealthy  aj)j)caranc-e.  In  many  cases 
a  large  ulcer,  covered  with  a  thick,  laminated  crust,  from  f)M(;-f|uarter  to 
one  inch  in  diameter,  followed  the  introduction  of  the  vaccine  matter 
into  scorbutic  patients."  In  the  same  report  Dr.  Paul  F.  Eve  describes 
certain  abnormal  manifestations  of  the  vaccine  disease  due  to  the  use 
of  an  improper  scab.  "The  scab  used  in  Atlanta  which  did  so  much 
mischief  was  soft,  porous,  and  spongy,  resembling  concrete  inspissated 

pus In  every  instance  in  which  vaccination  was  attempted 

with  it,  premature  effects  were  developed.  No  proper  period  of  incuba- 
tion nor  papular  nor  vesicular  eruption  was  observed,  but  in  a  few  days, 
even  as  early  as  the  second,  inflammation  had  set  up,  and  by  the  fourth 
or  fifth  day  sores  were  produced,  covered  by  a  thick,  dirty  crust,  with 
an  ichorous  discharge.  Soon  an  ill-constituted  ulcer,  with  perpendicular 
edges,  ensued,  extending  through  the  dermoid  to  the  cellular  and  mus- 
cular tissues,  and  involving  the  neighboring  lymphatics."  These  cita- 
tions indicate  that  either  a  weakened  resistance  on  the  one  hand,  or 
an  extraneous  infection  on  the  other,  may  be  responsible  for  vaccinal 
ulcerations. 

We  have  seen  a  few  cases  of  ulceration  at  the  vaccination  sites  follow- 
ing the  use  of  bovine  lymph.  Fig.  13  shows  such  an  ulceration  occur- 
ring about  the  fifteenth  day  after  vaccination. 

Septicaemia  and  Pyaemia  Following  Vaccination. — Blood  poisoning 
is  a  rare  condition  after  vaccination  at  the  present  day,  and  with  care  in 
the  propagation  and  preservation  of  lymph,  an  aseptic  technique,  and 
proper  protection  of  the  vaccinated  arm,  this  unfortunate  complication 
will  doubtless  become  rarer  still.  Several  appalling  epidemics  of  sep- 
tictemia  after  vaccination  are  on  record;  one  occurred  in  the  United 
States,  one  in  Germany,  and  one  in  France.  In  all  three  the  disastrous 
results  followed  the  use  of  humanized  virus;  in  two  instances  there  was 
the  grossest  negligence  in  the  preservation  and  preparation  of  the  crusts, 
and  in  the  third  a  lymph  was  used  which  was  producing  in  progressive 
transmissions  increasingly  abnormal  reactions. 

These  epidemics  are  of  much  importance,  and  a  brief  account  of  theui 
is  herewith  presented: 

In  1860,  during  the  prevalence  of  smallpox  in  Westford,  Massachu- 
setts, a  physician  vaccinated  a  number  of  people  with  crusts  which  had 
been  shaken  up  in  a  bottle  with  snow-water  in  order  to  provide  a  suffi- 
cient quantity  of  vaccine  material.  For  ten  or  eleven  days  patients  were 
vaccinated  with  a  lancet  which  was  from  time  to  time  dipped  into  the 
bottle.  None  of  these  people  showed  any  results;  but  on  the  eleventh 
or  twelfth  day,  by  which  time  the  bottle  of  liquid  emitted  a  horrible 
stench,  he  "vaccinated"  twenty-five  more  people.  There  at  once 
ensued  in  half  the  cases  diffuse  abscesses.  Three  of  the  oldest  vaccinees 
died  in  a  short  time,  and  a  dozen  or  more  of  the  remainder  were  only 
saved  by  the  most  prompt  and  energetic  treatment.^  As  Dr.  Martin, 
who  was  foreman  of  the  coroner's  jury  on  this  occasion,  stated,  "the 

1  Mentioned  by  Dr.  Henry  A.  Martin.    Reprint  from  a  letter  in  the  Erie  Observer. 

5 


QQ  VACCINIA 

fearful  results  were  clearly  to  be  ascribed  to  the  development  of  a  septic 
poison  of  intense  and  virulent  malignanty  at  a  certain  stage  of  the  de- 
composition of  animal  matter." 

In  1878,  at  Grabnick,  a  similar  but  more  extensive  epidemic  of 
septicaemia  occurred  among  children  infected  with  some  old  virus  which 
had  been  exposed  to  the  air  for  a  long  time.  Fifty-three  children  were 
inoculated  with  the  decomposed  vaccine  material,  and  of  this  number 
fifteen  died.  Some  of  the  children  had  morbilliform  and  scarla- 
tiniform  eruptions,  and  others  abscesses  and  erysipelatous  symptoms. 
According  to  Pincus  the  vaccine  material  contained  septic  bacteria. 
Autopsies  were  made  upon  two  children  and  the  deaths  ascribed  to 
septicaemia, 

BrouardeP  reports  a  series  of  cases  of  blood  poisoning  following 
vaccination  at  Asprieres,  France,  in  1885.  Brouardel,  Pasteur,  and 
Proust  were  commissioned  to  determine  the  responsibility  of  the  attend- 
ing physician.  The  commission  says:  "In  our  investigations  we  were 
enabled  to  trace  the  vaccine  back  through  five  generations  and  to  deter- 
mine that  it  was  by  employing  a  virus  originally  good,  but  which  gave 
rise  successively  to  accidents,  at  first  of  slight  gravity,  then  more  and 
more  serious,  that  the  preparation  was  made  for  the  final  disaster." 
Forty-two  children  were  vaccinated  from  the  arm  of  a  little  girl  who 
herself  had  developed  fever  the  first  night  after  her  vaccination,  and 
whose  vaccination  "took"  on  the  following  day.  Of  this  number  four 
died  within  twenty  hours  and  two  others  later.  Almost  all  of  those 
vaccinated  were  more  or  less  ill.  The  symptoms  were  fever,  vomiting, 
diarrhoea,  and  in  the  fatal  cases  convulsions.  The  fever  appeared  at 
the  latest  eighteen  hours  after  vaccination;  in  those  who  recovered  it 
lasted  from  two  to  four  days.  All  the  children  developed  on  the  first 
day  an  inflamed  area  about  1  cm.  in  diameter  surrounding  the  point 
of  inoculation.  A  serous  or  seropurulent  discharge  occurred  from  the 
first  to  the  third  day.  In  all  of  the  children  a  local  and  generalized 
impetiginous  eruption  followed  the  inoculation. 

These  cases  represent  examples  of  acute  intense  septicaemia  analo- 
gous to  that  resulting  from  bad  dissection  wounds.  The  septic  micro- 
organisms were  doubtless  increased  in  virulency  by  successive  trans- 
missions from  one  subject  to  another. 

A  case  of  pyoemia^  after  vaccination  is  recorded  in  the  Lancet,  1884, 
vol.  i.  p.  857.  A  child,  aged  six  months,  vaccinated  with  two  other 
children  from  the  same  source,  showed  on  the  ninth  day  appearances 
of  successful  vaccination  with  no  unusual  symptoms,  but  on  the  six- 
teenth day  the  sores  were  ulcerated  and  freely  discharging  pus.  The 
child  was  also  suffering  from  bronchitis.  Death  took  place  on  the 
twenty-fifth  day  after  vaccination.  The  autopsy  revealed  the  presence 
of  pus  in  the  left  ankle,  right  sternoclavicular  joint,  both  temporomaxil- 
lary  articulations,  and  in  the  bursa  over  the  right  olecranon.  The  lungs 
presented  a  number  of  hemorrhagic  infarcts. 

1  Twentieth  Century  Practice  of  Medicine.    Article  on  Vaccinia,  p.  534. 

2  Mentioned  by  Poole,  Vaccination  Eruptions,  Edinburgh,  1893,  p.  118. 


VyiC('fNAIj  (lOMI'lJdATIONS  AND  IN.iriilKS  07 

There  was  in  the  .same  house  a  man  vnfh  an  ah.srrs.s  of  llie  /oo/,  unci 
occasionally  \\w.  mother  had  washed  some  linen  in  the  water  which  Ijufl 
been  used  for  cleansinn;  his  foot.  This  fact,  with  the  early  normal  devel- 
opment of  the  vaccine  lesion,  and  the  exeinj)tif)n  of  th(;  other  two  chil- 
dren vaccinated,  constitute  strong  presumptive  evidence  that  the  septic 
infection  occurred  subsefjuent  to  vaccination,  probably  through  neglect 
on  the  part  of  the  child's  carelakers. 

Glandular  and  Subcutaneous  Abscess. — In  most  normal  vaccinations 
enlargement  and  tenderness  of  the  neighboring  lymj)hatic  glands  are 
observed.  Where  there  is  an  unusual  degree  of  inflammation  about  the 
vaccine  lesion  or  actual  ulceration,  the  swollen  glands  not  infre(juently 
undergo  suppuration.  As  has  been  already  stated,  glandular  abscess 
and  vaccinal  ulceration  comprised  nearly  4  per  cent,  of  vaccination 
injuries  reported  to  the  English  Local  Government  ]}oard  from  1888  to 
1S91.  Sinigar'  reports  four  cases  of  abscess  among  1160  vaccinations. 
One  appeared  on  the  twentieth  day  in  the  lower  half  of  the  posterior 
triangle  of  the  neck,  one  between  the  pocks  on  the  arm  on  the  twenty- 
fourth  day,  one  on  the  arm  on  the  twenty-ninth  day,  and  one  in  the 
axilla  on  the  thirty-second  day.  These  abscesses  are  seldom  of  serious 
portent,  usually  healing  rapidly  after  incision  and  evacuation. 

Localized  Vaccinal  Gangrene. — In  extremely  rare  instances  death 
of  the  tissues  eii  masse  at  the  site  of  vaccination  may  occur,  producing 
a  locahzed  gangrene.  It  would  seem  that  in  these  cases  the  gangrene 
is  due  to  low  vitahty  of  the  tissues  rather  than  to  any  impurity  of  the 
lymph.  In  cases  observed  by  Balzer,  Wheaton,  and  Acland,  the  chil- 
dren were  of  syphilitic  parentage.  Hutchinson,  however,  saw  three 
cases  of  vaccinal  gangrene  in  children  in  wdiom  no  such  cause  could  be 
invoked.  The  view  that  the  condition  of  the  tissues  is  the  most  important 
etiological  factor  in  the  production  of  this  complication  is  corroborated 
by  the  experience  of  surgeons  in  the  Confederate  army  during  the 
United  States  Civil  War.  Dr.  Joseph  Jones'  writes:  "After  careful 
inquiry  w^e  were  led  to  the  conclusion  that  these  accidents  were,  in  the 
case  of  Federal  prisoners,  referable  wdiolly  to  the  scorbutic  condition  of 
their  blood  and  the  crowded  condition  of  the  stockade  and  hospital. 
The  smallest  accidental  injuries  and  abrasions  of  the  surface,  as  from 
splinters  or  bites  of  insects,  were  in  a  number  of  instances  followed  by 
such  extensive  gangrene  as  to  necessitate  amputation.  The  gangrene 
following  vaccination  appeared  to  be  due  essentially  to  the  same  cause, 
and  in  the  condition  of  blood  of  these  patients  would  most  probably 
have  attacked  any  puncture  made  by  a  lancet,  without  any  vaccine 
matter  or  any  other  extraneous  material." 

Vaccinia  Gangraenosa. — As  has  been  pointed  out  by  Crocker  and 
others,  the  term  vaccinia  gangrrenosa  is  a  misnomer,  inasmuch  as  the 
affection  recorded  under  this  title  occurs  after  varicella  (varicella  gan- 
gnenosa)  and  other  discrete  pustular  eruptions.  Disseminated  necrosis 
of  the  skin  which  in  rare  instances  follows  vaccinia,  varicella,  and 

1  Lftiicot,  1902.  =  Report  of  Louisiana  Board  of  HeaUh,  ]&<^S4. 


68  VACCINIA 

pustular  dermatoses  may  occur  independently  of  these  diseases  in 
apparently  healthy  infants;  a  better  designation,  therefore,  for  this  con- 
dition is  dermatitis  gangroenosa  infantum.  The  gangrenous  changes  in 
the  skin  may  occur  early  or  late.  Stokes/  of  Dublin,  reports  a  case  of 
so-called  vaccinia  gangrgenosa  developing  forty-eight  hours  after  vac- 
cination. The  vaccinal  or  varicellous  pustules  may  be  directly  con- 
verted into  blackish  sloughs,  which  are  thrown  off  and  leave  deep,  ex- 
cavated ulcers;  or  the  gangrene  may  not  set  in  until  a  week  or  two  has 
elapsed,  beginning  as  papulopustules  which  crust  over,  become  sur- 
rounded by  an  areola,  and  then  break  down  and  ulcerate.  High  fever 
is  often  present.  The  cause  of  this  rare  condition  is  obscure;  it  usually 
supervenes  in  the  course  of  some  pustular  febrile  disease,^  particularly 
in  tuberculous,  syphilitic,  or  rachitic  children.  It  is  quite  possible  that 
the  gangrene  is  due  to  infection  with  some  virulent  micro-organism. 

Vaccinal  Roseola  (roseola  vaccinosa,  vaccinal  rash,  or  erythema). — 
Under  the  above  designations  has  been  described  a  rosy,  macular  rash, 
which  occasionally  appears  in  vaccinated  persons  about  the  time  of 
maturation  of  the  vesicle.  While  this  eruption  is  ordinarily  seen  about 
the  tenth  day  after  vaccination,  it  has  been  observed  as  early  as  the  third 
day  and  as  late  as  the  eighteenth.  It  usually  appears  first  upon  the 
vaccinated  arm,  rapidly  spreading  to  the  trunk  and  other  portions  of 
the  body.  The  macules  are  large,  irregular,  blotchy  in  appearance,  of 
a  rosy  tint,  and  not  elevated  above  the  level  of  the  skin.  In  rare  instances 
the  macules  may  coalesce,  giving  rise  to  a  diffuse  erythema.  The  erup- 
tion is  of  brief  duration,  lasting  from  a  few  hours  to  a  day  or  two.  It 
may  be  accompanied  by  moderate  elevation  of  temperature. 

The  rash  is  not  unlike  that  of  measles,  with  which,  indeed,  it  has  not 
infrequently  been  confounded.  The  eruption  of  measles  is  more  elevated, 
being  maculopapular  in  character  and  more  persistent,  and  is  accom- 
panied by  higher  fever  and  the  characteristic  catarrhal  symptoms  of  this 
disease. 

During  epidemics  of  smallpox,  vaccinal  roseola  has  been  mistaken 
for  the  beginning  eruption  of  confluent  smallpox.  Roseola  vaccinosa 
has  a  complete  analogue  in  the  roseola  variolosa,  an  exanthem  pre- 
senting almost  identical  features,  which  is  not  infrequently  observed 
just  before  the  appearance  of  the  eruption  of  modified  smallpox. 

Vaccinal  Lichen. — Crocker  states  that  in  his  experience  vaccine 
lichen  has  been  the  most  common  of  the  true  vaccinal  exanthema.  He 
has  made  notes  of  twenty  cases  of  this  eruption.  He  states  that  it  may 
be  either  papular,  papulovesicular  or  pustular.  It  appears  from  the 
fourth  to  the  eighteenth  day,  most  commonly  on  the  eighth;  in  about 
one-half  the  cases  it  is  seen  first  on  the  arms,  appearing  in  the  remainder 
on  the  trunk,  neck,  or  face;  the  eruption  then  extends  in  successive 
crops  over  large  portions  or  the   entire   cutaneous    surface  (Fig.  14). 

1  Dublin  Journal  of  Medical  Science,  June,  1880.    Quoted  by  Crocker. 

2  The  writers  recall  the  case  of  a  young  girl  suffering  from  smallpox,  who  developed  at  the  end  of 
the  third  week  numerous  punched-out  areas  of  cutaneous  gangrene.  Tlie  patient  succumbed  to  this 
complication,  which  was  doubtless  a  condition  analogous  to  the  so-called  vaccinia  gangreenosa. 


PLATE  III. 


Roseola  Vaccinosa  Appearing  upon  the  Tenth  Day 
after  Vaccination. 


VA(J(!/NAIj  aOMI'LKIATIONS  AND  IN.IUIUI'IS 


69 


The  j);i,j)nl(',s  urc  rcuhJisli,  (-(Hiic^al,  piiilicad  .siz(;(J,  .siinoiiiidcd  hy  a 
reddisli  halo,  and  often  surmounted  by  minute  vesicles  or  pustules. 
In  the  experience  of  the  writers  vaccine  lichen  has  l)een  excessively 
rare. 

KiG.  H 


VacciuiUion  upon  the  tenth  da}',  showing  an  unusually  inteiife  areola.    A  papular  vaccinal 
eruption  is  also  seen  upon  the  face. 

Vaccinal  Miliaria. — In  rare  cases  instead  of  a  papular  eruption  a 
vesicular  outbreak  may  take  place,  usually  from  the  eighth  to  the  eleventh 
day.  Danchez^  writes:  "We  give  the  name  vaccinal  miliaria  to  a  satel- 
lite eruption  of  the  vaccinal  fever,  appearing  from  the  eighth  to  the  twelfth 
day  (very  rarely  later)  after  vaccination.  It  is  constituted  by  small  vesi- 
cles of  the  size  of  a  grain  of  millet,  accumulated  in  great  numbers  over 
large  surfaces,  containing  a  transparent  liquid  at  first,  then  opaque,  fol- 
lowed by  slight  furfuration,  and  never  leaving  cicatrices  after  it." 

1  Vaccinides,  "^hHe  de  Paris,  1SS3. 


70  VACCINIA 

A  miliary  vesicular  eruption  is  occasionally  seen  in  or  around  the 
vaccination  areola.  These  vesicles  are  not  true  vaccine  lesions,  for 
Martin  has  shown  that  the  contents  inoculated  upon  another  individual 
fails  to  produce  the  vaccine  disease. 

Erythema  Multiforme  and  Urticaria  after  Vaccination. — The  erup- 
tion of  multiform  erythema  is  occasionally  seen  in  vaccinated  individuals 
between  the  first  and  the  tenth  day  after  the  insertion  of  the  virus.  In 
some  cases  the  eruption  is  delayed  considerably  beyond  this  period. 
The  lesions  may  be  erythematous,  papular,  tuberculous,  vesiculobullous 
or  mixed. 

At  times  the  eruption  is  annular.  Crocker  saw  a  well-marked  case 
which  began  on  the  ninth  day  after  vaccination,  and  was  characterized 
by  shilling-sized  annulopapular  patches.  Napier  observed  a  case  on 
the  eleventh  day  which  began  as  rings. 

Not  infrequently  urticarial  lesions  are  present,  the  eruption  being 
a  type  of  combined  erythema  multiforme  and  urticaria.  Allen  and 
Sobel  regard  urticaria  as  one  of  the  most  common  of  the  generalized 
vaccinal  eruptions. 

Norman  Walker^  has  observed  five  cases  of  erythema  multiforme  after 
vaccinations  with  glycerinated  lymph.  In  all,  the  early  course  of  the 
vaccination  was  uneventful.  The  eruption  was  invariably  seen  on  the 
hands  and  face,  but  on  other  parts  as  well. 

In  a  review  of  the  vaccinal  complications  in  1160  vaccinations,  Sinigar^ 
states  that  there  were  23  cases  of  erythema,  including  simple  erythema- 
tous blushes,  finely  punctate  erythemata,  erythema  of  papular  or  urti- 
carial type,  and  erythema  multiforme.  Concerning  the  date  of  appear- 
ance, 1  rash  appeared  on  the  third  day,  5  on  the  eighth,  2  on  the  ninth, 
5  on  the  tenth,  4  on  the  eleventh,  1  on  the  twelfth,  4  on  the  thirteenth, 
and  1  on  the  sixteenth  day.  No  age  was  exempted ;  in  4  cases  the  patient 
was  over  seventy  years  of  age.  The  average  duration  of  the  rash  was 
forty-eight  hours,  but  in  1  severe  case  it  lasted  six  days. 

Impetigo  Contagiosa. — This  contagious  disease  of  the  skin  is  ex- 
tremely common,  independent  of  vaccination,  among  dirty  and  poorly 
nourished  children.  Any  abrasion  of  the  skin  increases  the  liability 
to  its  development.  Its  occasional  occurrence  after  vaccination,  par- 
ticularly among  children  in  poor  hygienic  circumstances,  is  therefore 
scarcely  to  be  marvelled  at.  The  introduction  of  the  infection  of  impetigo 
with  the  insertion  of  the  vaccine  virus  must  be  an  occurrence  of  the 
greatest  rarity;  inasmuch  as  impetigo  sores  develop  rapidly  (from  one  to 
two  days)  after  the  skin  is  infected,  we  would  expect,  if  the  disease  were 
invaceinated,  to  discover  the  impetigo  lesions  twenty-four  to  forty- 
eight  hours  after  the  vaccination. 

As  a  matter  of  experience,  however,  impetigo  usually  develops  at  a 
considerably  later  period;  it  may  make  its  appearance  at  any  period 
up  to  the  complete  healing  of  the  vaccinal  wound.  It  is  not  infrequently 
observed  at  the  end  of  the  second  or  third  week  after  vaccination.    The 

1  British  Medical  Journal,  1901,  p.  1201.  2  Lancet,  1902. 


VyiCC/Nyil.  aoMI'LldATIONH  AND  I  S.I  IJ  III  HS 


71 


first  lesions  are  usually  seen  about  the  site* of  iusertirtn  (jf  the  vaeciiK- 
lyriipli.  This  area  may  heeoine  quitc^  irifiain(!(l,  the  surrounding  epi- 
dermis raised  up  by  a  seropurulent  fluid,  and  the  process  extend  upon 
the  periphery,  with  the  production  of  voluminous  ochre-colored  crusts. 
From  this  as  a  focus  other  ])ortions  of  the  skin  become  infected  by 
aut()ino(nilation  through  scratchinn;  or  other  means.  At  times  impetigo 
may  assume  a  bullous  form,  simulating  ])emphigus;  most  oF  the  pem- 


Secondary  impetigo  engrafted  upon  a  late  vaccination  and  subsequently  upon  other  regions. 


phigoid  eruptions  after  vaccination  would  appear,  however,  to  belong 
to  the  group  of  bullous  dermatitis  presently  to  be  described.^ 

In  1885  an  outbreak  of  a  cutaneous  disease,  said  to  have  presented 
the  clinical  features  of  impetigo,  occurred  in  villages  on  the  Island  of 
Rtigen,  in  the  Baltic  Sea,  after  the  vaccination  of  seventy-nine  children. 

'  Engman  and  Grindon  have  each  described  (Journal  of  Cutaneous  and  Genito-urinary  Diseases, 
1901,  pp.  180  and  188)  extensive  cases  of  bullous  impetigo,  not,  however,  related  to  vaccination. 
They  state  that  this  form  of  the  disease  is  quite  common  in  St.  Louis,  and  that  epidemics  occasionally 
occur  in  foundling  asylums,  attacking  particularly  weak  and  undernourished  infants.  Some  of  the 
cases  reported  terminated  fatally.  [The  differential  diagnosis  between  bullous  impetigo,  acute 
pemphigus,  and  dermatitis  herpetiformis  is  sometimes  fraught  with  difficulty.] 


72  VACCINIA 

Impetigo  contagiosa  is  caused  by  invasion  of  the  skin  with  the  germs 
of  contagious  pus,  independently  of  its  source.  There  are  probably  two 
chief  varieties  due  respectively  to  the  streptococcus  and  the  staphylococ- 
cus pyogenes. 

Vaccinal  Erysipelas. — Erysipelas  is  an  acute  infectious  disease 
resulting  from  invasion  of  the  body  with  the  streptococcus  of  Fehleisen. 
In  the  vast  majority  of  cases  of  this  malady  the  infection  gains  its 
entrance  to  the  system  through  a  wound  of  the  cutaneous  or  mucous 
surfaces;  the  disease  therefore  is  essentially  a  wound  infection. 

Inasmuch  as  vaccinia  is  attended  with  the  production  of  a  wound  of 
the  skin,  it  is  not  surprising,  particularly  in  view  of  the  frequent  neglect 
of  vaccination  wounds,  that  erysipelas  should  occasionally  occur  after 
this  procedure.  The  erysipelatous  infection  is  usually  conveyed  to  the 
vaccination  wound  at  some  period  subsequent  to  the  insertion  of  the 
vaccine  virus;  in  rare  cases,  however,  the  specific  germs  of  erysipelas 
may  be  present  in  the  lymph,  in  which  event  this  complication  develops 
on  the  second  or  third  day  after  vaccination. 

Erysipelas  may  develop  in  an  infant  after  vaccination  and  still  be 
independent  thereof.  Erysipelas  is  a  common  disease  among  infants; 
according  to  Dr.  Ogle's  testimony  before  the  British  Royal  Vaccination 
Commission,  two  thousand  per  million  infants  under  three  months  of 
age  perish  from  it.  It  has  been  known  to  develop  after  very  trivial 
injuries,  such  as  the  scratch  of  a  pin,  abrasion  from  the  friction  of 
clothing,  etc. 

Both  vaccinal  erysipelas  and  erysipelas  from  other  causes  are  attended 
with  a  rather  high  mortality  rate  in  infants.  Of  the  deaths  attributed 
to  vaccination  in  England  between  1886  and  1891  almost  one-half 
resulted  from  erysipelas. 

Erysipelas  may  result  from  the  employment  of  lymph  containing 
streptococci,  from  infected  instruments,  unclean  hands,  contact  of 
soiled  linen,  or  from  previous  contamination  of  the  skin  at  the  vaccina- 
tion site.  When  the  disease  develops  late  it  is  often  favored  by  injury 
or  rupture  of  the  vesicle,  or  forcible  and  premature  detachment  of  the 
crust.  Bad  hygienic  surroundings  and  uncleanliness  of  the  body  or 
garments  increase  the  liability  to  infection.  Humanized  lymph  derived 
from  a  vaccinifer  with  an  inflamed  arm  may  give  rise  to  erysipelas. 
The  improper  preservation  of  crusts  has  likewise  given  rise  to  some 
cases.  One  of  the  writers  saw  some  years  ago  a  series  of  cases  of  ery- 
sipelas follow  vaccination  with  a  humanized  crust  which  had  been 
rubbed  up  with  water  and  kept  in  the  pocket  between  two  glass  slides 
for  several  days,  during  which  time  decomposition  had  taken  place. 

As  a  vaccinal  complication,  erysipelas  appears  to  be  distinctly  on  the 
decrease.  In  1877  Lotz  was  able  to  collect  in  Germany  but  two  cases 
of  death  from  this  cause  in  1,252,554  vaccinations. 

The  increased  attention  to  asepsis  in  vaccination,  the  careful  protec- 
tion of  the  vesicle  when  formed,  and  the  employment  of  bovine  lymph 
will  doubtless  continue  to  lessen  the  frequency  of  this  complication. 

It  is  claimed  that  animal  virus,  on  account  of  the  comparative  insus- 


VACOfNAL  (!()M/'/J(!AT/()NS  AND  IN.HHill-lS  70 

ceptibility  of  the  bovine  species  to  erysipelas,  gives  a  greater  security 
affainst  this  disease  than  humanized  virus.  In  1877  II.  A.  Martin 
emphasized  this  advantage  of  animal  lymph  in  the  most  positive  terms. 
He  Mfrote:  "During  the  sixteen  years  in  which  I  snpj)li(;d  humanized 
virus  the  presence  of  this  pest  (erysipelas)  in  my  prac-tice  and  in  that 
of  my  correspondents  w^as  the  one  great  and  serious  drawback,  the  one 
formidable  source  of  anxiety  and  blame.  Since  I  have  issued  bovine 
virus  to  a  far  greater  extent  (from  eight  to  nine  thousand  corre- 
spondents),! have  never  received  a  single  complaint  of  the  (n-crurrence 
of  erysipelas.  It  is  said  to  attack  particularly  cases  of  revaccination, 
but  in  1872-73  I  revaccinated  about  twelve  thousand  patients  with  my 
own  hand,  and  there  was  not  one  case  of  erysipelas  among  them  all, 
nor  have  I  ever  known  a  case  following  the  use  of  the  bovine  virus  at 
any  other  time."  Martin  abandoned  the  collection  and  propagation 
of  humanized  virus  in  1873  because  in  one  week  he  had  five  cases  of 
erysipelas.  These  children  were  vaccinated  on  one  arm  with  the  hum  an- 
ized  lymph  and  on  the  other  with  the  bovine  product,  and  in  each  in- 
stance erysipelas  appeared  on  the  arm  on  which  humanized  virus  had 
been  employed. 

True  vaccinal  erysipelas  should  be  trenchantly  distinguished  from 
the  dermatocellulitis  which  is  not  infrequently  observed  about  the  vac- 
cine lesion,  and  which  occasionally  involves  the  entire  upper  arm  and 
even  the  forearm;  this  is  nothing  more  than  an  exaggeration  of  the 
inflammatory  areola.^  The  arm  is  swollen  and  intensely  reddened, 
but  there  is  no  tendency  for  the  process  to  spread  to  other  parts  of  the 
body,  the  inflammatory  phenomena  subsiding  after  the  height  of  the 
vaccinia  has  been  reached. 

Tetanus  Following  Vaccination. — The  development  of  lockjaw 
after  vaccination  was  until  a  few  years  ago  an  occurrence  of  the  greatest 
rarity.  The  minority  contingent  of  the  British  Royal  Vaccination  Com- 
mission in  1896,  after  extended  investigation,  was  able  to  mention  but 
a  single  instance  of  this  complication. 

Tetanus  after  vaccination  is  said  to  be  unknown  in  France,  Germany, 
and  other  continental  countries  of  Europe.  Within  the  past  five  years 
(and  particularly  in  1901)  a  rather  alarming  number  of  cases  has  been 
reported  in  the  United  States.  Dr.  R.  N.  Willson  and  Dr.  Joseph 
McFarland^  have  independently  presented  analytical  studies  of  all  of 
the  cases  recorded  and  of  other  cases  personally  communicated  to  them. 
Willson  reports  52  cases  and  McFarland  95,  28  of  which,  however,  are 
shrouded  in  considerable  doubt. 

Willson,  from  a  painstaking  study  of  the  records  of  the  cases  reported, 
came  to  the  conclusion  that  while  the  tetanus  infection  gained  entrance  at 
the  site  of  vaccination,  it  was  not  introduced  with  the  vaccine  ^-irus,  but 
at  some  period  subsequent  to  this. 

1  Some  of  the  older  writers,  including  Jenner,  referred  to  this  condition  under  the  rather  mislead- 
ing designation  of  "erysipelatous  inflammation  ;"  but,  as  Jenner  himself  explains,  it  was  not  regarded 
as  true  erysipelas,  but  as  merely  bearing  a  resemblance  to  it. 

2  Proceedings  of  the  Philadelphia  County  ^Medical  Society,  September,  1902. 


74  VACCINIA 

McFarland,  on  the  other  hand,  beHeves  that  tetanus  organisms  may 
be  present  in  the  virus,  being  derived  from  manure  and  hay;  he  further 
states  that  the  future  avoidance  of  the  comphcation  is  to  be  sought  for 
in  greater  care,  in  the  preparation  of  the  virus. 

In  October,  November,  and  December,  of  1901,  there  v^^as  a  small 
epidemic  of  tetanus  after  vaccination  in  Camden,  Philadelphia,  and 
to  a  certain  extent  in  some  nearby  towns.  Camden  had  11  cases,  and 
Philadelphia  even  more  than  this  number.  These  groups  of  cases 
have  been  adduced  as  evidence  in  favor  of  the  view  that  the  tetanus 
infection  is  in  the  virus.  Willson,  however,  shows  that  there  occurred 
in  Philadelphia  during  the  above  period  12  cases  of  tetanus  inde- 
pendent of  vaccination.  In  Baltimore  during  the  month  of  August 
there  were  6  cases  of  tetanus  independent  of  vaccination,  in  September 
6  cases,  and  in  October  (the  month  in  which  the  Camden  outbreak 
occurred)  8  cases. 

In  1899,  in  New  York  City,  there  were  63  deaths  from  tetanus 
unrelated  to  vaccination;  in  Philadelphia,  in  1901,  there  were  29 
deaths  from  similar  cases,  and  in  Cook  County,  Illinois,  from  June 
25  to  July  14,  1900,  27  deaths  from  tetanus  from  causes  other  than 
vaccination.  In  1903  there  occurred  throughout  the  United  States  406 
deaths  from  tetanus  as  a  result  of  wounds  received  on  the  Fourth  of 
July  from  toy  pistols  and  blank  cartridges  (special  article  in  Journal  of 
the  American  Medical  Association).  These  figures  indicate  that  such 
epidemics  of  tetanus  as  occurred  after  vaccination  in  Philadelphia  and 
Camden  might  readily  have  developed  from  other  causes. 

Improper  care  of  the  vaccine  wound  and  the  development  of  exces- 
sive inflammation  and  ulceration  appear  to  be  important  factors  in 
predisposing  to  tetanus  infection.  Willson  says:  "In  every  instance 
in  the  series  of  cases  included  in  this  paper,  in  which  any  information 
could  be  obtained  whatsoever,  there  has  been  found  some  gross  breach 
in  the  care  of  the  wound,  and  usually  the  presence  of  some  active  influ- 
ence that  would  offer  more  than  a  likely  means  of  entrance  for  tetanus 
or  any  other  infection."  "  Nearly  every  case  showed  for  days  a  large 
open  ulcer,  burrowing  deep  into  the  tissues.  Two  cases  were  those  of 
soldiers,  sleeping  anywhere  and  everywhere,  and  looking  on  a  bath  as 
a  luxury.  Several  children  lived^over^  and  next  to  and  played  continually 
in  stables,  the  hotbed  of  the  tetanus  bacillus.  One  slept  in  bed  every 
night  with  her  father,  who  had  charge  of  horses.  Two  at  least  are  known 
to  have  forcibly  maltreated  the  vaccine  wound.  Many  removed  the 
scab  for  inspection.  Two  threw  or  dropped  the  scab  on  the  ground 
and  replaced  it  in  the  wound,  one  wearing  it  for  hours.  One  threw  his 
bandage  on  the  ground  and  replaced  it  on  the  arm  at  a  later  time. 
Several  wore  a  shield  over  the  wound  without  cleansing  or  removing 
it  until  it  was  full  of  pus  and  dirt  and  foul  to  smell;  one  of  these  reached 
the  eighteenth  day  and  the  writer's  case  the  twenty-eighth  with  the 
shield  still  in  place.  One,  when  tetanus  developed,  exhibited  a  merino 
shirt-sleeve,  that  had  never  been  washed,  matted  in  the  vaccine 
wound." 


VAddlNAIj  (JOMI'IjICATIONS  AND   IS'.HIIHI-IS  75 

Rosenau/  in  a  study  of  the  bacterial  impurities  of  vaeoirif;  virus,  was 
uiiahle  to  find  tetaruis  or(>;anistns  in  any  of  a  consi<Jcral)l(;  nuinhcr  of 
glycerinated  points  and  tubes  bouglit  in  open  market  and  examined 
with  this  object  in  view.  He  states  that  tetanus  organisms  cannot  grow 
or  produce  their  toxin,  either  in  glycerinated  virus  or  on  dry  points. 
"It  would  take  gross  carelessness  to  c;ontaniinate  the  vaccine  with  a 
sufficient  number  of  tetanus  S])ores  to  carry  the  disease  to  those;  vacci- 
nated. It  is  not  a  matter  of  surprise  that  some  outbreaks  of  tetanus 
have  occurred  when  thousands  of  open  wounds  are  presented  for  the 
reception  of  this  infection  so  widely  distributed  in  nature." 

Considering:  the  hundreds  of  thousands  of  vaccinations  which  are 
performed  each  year,  and  the  neglect  of  the  vaccination  wound  on  the 
part  of  many  persons,  the  wonder  is  that  not  more  cases  of  tetanus 
develop.  Where  the  vaccinia  runs  a  perfectly  normal  course,  and  the 
vesicle  is  uninjured  and  the  crust  undisturbed,  tetanus  is  much  less 
prone  to  develop.  Tetanus  would  appear  to  occur  no  oftener — if  as 
often — after  vaccination  than  after  ordinary  cutaneous  wounds. 

The  usual  period  of  incubation  of  traumatic  tetanus  is  from  seven 
to  nine  days.  The  average  period  of  incubation  of  the  reported  cases 
of  tetanus  after  vaccination  is  twenty-two  to  twenty-three  days.  Among 
Willson's  cases,  45  developed  tetanus  fourteen  days  or  more  after 
vaccination;  31,  twenty  days  or  more  after  vaccination;  1,  twenty-eight 
days  after  vaccination,  and  1,  at  the  end  of  seven  weeks. 

The  effort  has  been  made  to  explain  the  late  onset  of  tetanus  by 
assuming  that  the  tetanus  germs  lie  dormant  in  the  skin  until  the  vac- 
cinia reaches  the  stage  when  tissue  destruction  takes  place.  It  is  thus 
attempted  to  explain  the  two  weeks'  delay  in  the  appearance  of  the 
symptoms  of  tetanus. 

In  at  least  three  instances  in  which  tetanus  followed  vaccination  the 
same  virus  was  used  upon  other  persons  in  addition  to  the  one  that 
developed  the  disease.  In  a  case  investigated  by  the  British  Royal 
Vaccination  Commission  "a  female  child,  aged  two  months,  developed 
trismus  on  the  twenty-third  day  after  vaccination.  This  child  was 
vaccinated  from  the  arm  of  a  female  infant,  aged  five  months,  and  at 
the  same  time  and  with  the  same  lymph  six  other  children  irere  vaccinated, 
and  none  of  them  developed  tetanus  or  sore  arms." 

In  a  case  of  tetanus  occurring  in  a  woman  aged  twenty-one  years, 
reported  by  Drs.  William  Findlay  and  J.  W.  Findlay,'  several  people 
were  inoculated  with  virus  from  the  same  tube,  but  none  save  the  one 
patient  developed  tetanus.  In  one  of  the  Camden  cases  the  patient's 
"brother  was  vaccinated  from  the  same  tube,  the  vaccination  proving 
3uccessful  and  normal."  These  cases  would  certainly  seem  to  indicate 
that  the  tetanus  organisms  were  not  derived  from  the  vaccine  ^-i^us 
employed. 

Tetanus  germs  are  found  in  abundance  in  garden  soil  and  street  dirt ; 

1  Director  of  the  Hygienic  Laboratory  of  tlie  United  States  Public  Health  and  Marine  Hospital 
Service,  Bulletin  12, 1903. 

2  Lancet  February  22, 1902. 


76  •      VACCINIA 

they  are  commonly  present  in  the  manure  of  herbivorous  animals,  but 
to  a  much  less  extent  in  the  excrement  of  suckling  calves.  Huddleston, 
of  New  York,  found  them  in  8  per  cent,  of  the  calves  used  in  the  labo- 
ratory of  the  New  York  Health  Department. 

While  the  contamination  of  vaccine  virus  with  tetanus  germs  must 
be  admitted  as  a  possibility,  we  believe,  from  a  study  of  the  recorded 
instances  of  this  complication,  that  the  tetanus  infection  was  in  the 
great  majority  of  cases  received  into  the  system  at  a  period  sub- 
sequent to  the  insertion  of  the  lymph.  About  three-quarters  of  the 
cases  of  tetanus  after  vaccination  have  proved  fatal. 

Vaccinal  Syphilis.— The  study  of  vaccinal  syphilis  has  been  bereft 
of  much  of  its  importance  since  the  general  adoption  of  calf-lymph  for 
vaccination.  Inasmuch  as  the  bovine  species  is  totally  insusceptible 
to  the  syphilitic  infection,  it  is  obviously  impossible  to  convey  this 
poison  by  vaccination  with  lymph  from  this  source.  It  has  been  sug- 
gested that  syphilis  might  be  conveyed  in  the  vaccine  virus  as  a  result 
of  a  syphilitic  vaccinator  expelling  the  lymph  through  the  capillary 
tube  with  his  breath,  but  this  is  a  purely  gratuitous  assumption,  entirely 
without  any  clinical  evidence. 

With  the  employment  of  humanized  virus  and  particularly  with  arm- 
to-arm  vaccinations,  it  must  be  frankly  admitted  that,  though  relatively 
of  extremely  rare  occurrence,  it  is  possible  to  convey  the  syphilitic 
poison.  The  infrequency  of  this  lamentable  accident  may  be  com- 
prehended when  it  is  stated  that  Dr.  Robert  Lee  saw  but  one  case  of 
supposed  vaccinal  syphilis  among  30,000  children  at  the  Hospital  for 
Sick  Children,  Great  Ormond  Street,  London,  an  institution  particu- 
larly likely  to  attract  cases  of  syphilis.  At  the  East  London  Hospital 
for  Children,  Dr.  Radcliffe  Crocker,  although  for  many  years  on  the 
lookout  for  such  cases,  never  observed  a  single  instance  of  vaccinal 
syphilis. 

In  1856  the  London  Board  of  Health  collated  the  experiences  and 
opinions  of  a  large  number  of  prominent  physicians  concerning  vaccinal 
syphilis.  None  of  the  respondents  were  able  to  present  any  convincing 
facts,  and  a  large  majority  expressed  complete  incredulity  as  to  its 
occurrence.  The  English  Royal  Vaccination  Commission,  referring 
to  this  incident,  remarks:  "It  is  impossible  to  believe  that  an  event 
concerning  the  possibility  of  which  almost  all  the  leaders  of  the  pro- 
fession were  in  1856  incredulous  can  be  otherwise  than  extremely  rare." 

The  commission  in  its  judicial  sessions  examined  many  physicians 
who  had  extensively  practised  vaccination  for  many  years,  and  who 
had  never  personally  observed  vaccination  syphilis  themselves  or 
heard  of  it  in  the  immediate  practices  of  their  colleagues. 

Nevertheless,  the  fact  must  be  admitted  that  cases  of  syphilitic  infec- 
tion have  resulted  through  vaccination  from  arm  to  arm.  While  the 
number  of  such  cases  is  infinitesimally  small  when  compared  with  the 
enormous  number  of  vaccinations  performed,  the  aggregate  number 
of  cases  of  invaccinated  syphilis  on  record  throughout  the  past  century 
is  not  inconsiderable. 


VA  C'fJ  fNA  L  (I  OMP  L  Id  A  770  ^,S'  AND  I  N.I  URI KS  7  7 

Epidemics  of  vaccinal  ,syj)liiiis  have  hecii  olisT'.cd  iiiid  ic[)(>rtc(l 
by  Marcolini  (IS]4  in  IJdinej,  Cerioli  (1SI2  in  Crenioiia;,  'Jassani 
(1841  in  (innnello),  Wetreler  (1840  in  Coblentzj,  Oherfianken  i\^',2 
in  Freienfels),  Marone  (18r>()  in  Liipaiaj,  J'accliiotti  fhSf))  in  liivaltaj, 
Depaul  (18GG  in  Morbihan,  France),  Kocevar  (1870  in  Schleinitz  and 
St.  Veix),  Jonathan  Hutchinson  (1871  in  London,  two  series  of  cases), 
and  I>ayet  (1880  in  Algiers  and  1885  in  Turin). 

A  brief  account  of  the  Rivalta  and  Lupara  epidemics,  which  are 
fairly  typical  of  all  the  rest,  is  herewith  subjoined: 

In  1801  Pacchiotti^  reported  an  extensive  epidemic  of  vaccinal  sy}>hilis 
occurring  in  Rivalta,  Italy:  46  children  were  vaccinated  from  the  origi- 
nal vaccinifer;  of  these  40  contracted  syphilis.  From  1  of  these  subjects 
7  other  children  became  infected  through  vaccination.  In  a(lditif)n  20 
mothers  or  nurses  contracted  syphilis  through  contact  with  these  children. 
But  17  out  of  G3  vaccinees  escaped  infection. 

About  the  same  time  Marone^  published  an  account  of  a  similar 
epidemic  that  occurred  at  Lupara  in  1856.  A  large  number  of  infants 
were  vaccinated  with  humanized  lymph  received  in  tid)es  from  Campo- 
basso,  and  23  were  infected  with  syphilis.  From  1  of  these  children  1 1 
other  infants  were  inoculated  with  the  disease.  As  in  the  Rivalta  tragedy, 
a  number  of  mothers  and  nurses  subsequently  developed  chancres  of  the 
nipple. 

It  will  be  seen  that  more  than  half  of  the  cases  of  vaccinal  syphilis 
that  have  been  recorded  have  occurred  in  Italy.  The  remainder  have 
been  found  in  France,  Germany,  and  England.  Fortunately,  such 
infections  in  the  United  States  have  been  extremely  rare.  It  has  been 
estimated  that  the  aggregate  number  of  cases  of  vaccinal  syphilis  that 
have  occurred  is  about  seven  hundred.  When  we  think  of  the  millions 
of  lives  that  have  been  saved  by  vaccination  during  the  past  century, 
we  recognize  the  fact  that  the  sacrifices,  however  deplorable,  have  been 
relatively  small.     Many  blessings  are  leavened  with  misfortune. 

Pacchiotti,  in  1861,  laid  down  the  following  rules  to  be  observed  in 
vaccinating:  1.  Enquire  into  the  state  of  the  patient's  health.  2.  Take 
the  lymph  in  preference  from  those  children  who  have  passed  the  fourth 
or  fifth  month,  as  hereditary  syphilis  appears,  in  general,  before  that  time. 
3.  Do  not  use  lymph  taken  from  a  vesicle  which  has  passed  its  eighth 
day,  because  on  the  ninth  and  tenth  days  the  lymph  becomes  mixed 
with  pus,  which  later  may  be  of  an  infectious  character.  4.  In  taking 
the  lymph,  avoid  hemorrhage,  as  there  is  less  danger  with  hiiiph  free 
from  blood.  5.  Do  not  vaccinate  too  many  children  with  the  same 
lymph. 

The  observance  of  these  precautions  would  obviate  much  of  the  risk 
of  transmitting  syphilis,  but  would  not  confer  absolute  security  against 
such  infection.  The  British  Royal  Commission  on  Vaccination  says: 
"Absolute  freedom  from  risks  of  syphilis  can  be  had  only  when  calf- 

1  Sifilide  Transmissa  per  Mezzo  Delia  Vaceiiiazione  in  Rivalta  Presso  Acqui.    Gazetta  Delia  Asso 
ciazlone  Meri.,  October  20,  l^Bl. 
s  Impraziale  de  Florence,  November  5,  1862. 


78  VACCINIA 

lymph  is  used,  though  where  the  antecedents  of  the  vaccinifer  are  fully 
ascertained,  and  due  care  is  used,  the  risk  may  for  practical  purposes 
be  regarded  as  absent." 

Inasmuch  as  bovine  virus  is  at  the  present  time  generally  and,  indeed, 
almost  universally  employed,  the  subject  of  syphilis  may  be  dismissed 
in  a  discussion  of  the  complications  of  vaccination. 

The  employment  of  calf-lymph  and  the  complete  elimination  of  the 
risk  of  transferring  syphilis  to  the  vaccinee  have  robbed  the  opponents 
of  vaccination  of  one  of  their  most  potent  arguments  against  the  enforce- 
ment of  vaccination. 

The  Relation  of  Vaccination  to  Tuberculosis. — Whether  or  not  it 
is  possible  to  transmit  tuberculosis  in  vaccine  lymph  is  an  undeter- 
mined question.  Toussaint^  claims  to  have  successfully  inoculated 
rabbits  and  a  pig  w^ith  tuberculosis  with  lymph  taken  from  a  vaccine 
vesicle  induced  upon  the  vulva  of  a  tuberculous  cow.  On  the  other 
hand,  Josserand^  injected  lymph  taken  from  vaccine  vesicles  in  tuber- 
culous individuals  into  the  peritoneal  cavity,  under  the  skin,  and  into 
the  anterior  chamber  of  the  eye  in  47  animals.  Post-mortem  exami- 
nations gave  absolutely  negative  results  in  43  of  these,  and  in  no 
animal  was  there  conclusive  evidence  of  tuberculosis. 

The  danger  of  conveying  tuberculosis  in  bovine  lymph  is  almost 
inappreciable.  The  virus  is  obtained  from  calves,  and  it  is  pretty  well 
established  that  calves  are  but  rarely  the  subjects  of  tuberculosis.  It 
is  stated  by  Fiirst,  on  the  authority  of  Pfeiffer,  that  but  one  case  of 
tuberculosis  was  found  among  34,400  calves  under  four  months  of  age.^ 
The  statistics  of  the  abattoirs  of  Augsburg  and  Munich  corroborate 
the  above  figures;  only  one  tuberculous  calf  was  discovered  at  Augs- 
burg among  22,230  slaughtered,  and  a  smaller  percentage  at  Munich.'' 

Furthermore,  in  well-regulated  vaccine  establishments  calves  are 
subjected  to  the  tuberculin  test  before  vaccination,  and  are  autopsied 
before  the  lymph  is  distributed  for  use.  Even  though  it  were  possible, 
despite  these  precautions,  for  tubercle  bacilli  to  get  into  the  lymph,  they 
would  perish  if  the  lymph  were  glycerinated.  Copeman,^  speaking  of 
glycerinated  lymph,  says :  "  The  tubercle  bacillus  is  effectually  destroyed 
even  when  large  quantities  of  virulent  cultures  have  been  purposely 
added  to  the  lymph." 

Bollinger,  Heron,  and  Acland  all  seriously  doubt  whether  tubercu- 
losis has  ever  been  transmitted  by  vaccination. 

Postvaccinal  Lupus  Vulgaris. — Cases  of  lupus  occurring  in  and 
around  vaccination  scars  have  been  reported  by  I^enander,  Besnier," 
Perry,''  Little,^  Colcott  Fox,  x^cland,^  Stelwagon,^"  and  others.     Most  of 

1  French  Academy  of  Sciences,  August  8,  1881,  quoted  by  Acland,  Allbutt's  System  of  Medicine, 
p.  619. 

2  Contribution  a  Tetude  des  contamination  vaccinales,  Lyons,  1884,  p.  30,  quoted  by  Aclaud. 

3  Fiirst.    DiePathologiederSchutz-Pocljen-Impfung,  Berlin,  1896,  par.  431,  p.  112,  quoted  by  Acland. 
*  Strauss.    Gaz.  hebdom.  de  mod.  et  de  chirurg.,  1885,  p.  143,  quoted  by  Acland. 

s  Vaccination,  its  Natural  History  and  Pathology,  London,  1899,  p.  181. 

8  Annales  de  dermat.  et  de  syph.  1889,  p.  576.  ?  British  Journal  of  Dermatology,  1898,  )>.  r.m, 

8  Ibid.,  1900,  p.  60.  «  Loc.  cit. 

'"  Journal  of  the  American  Medical  A.ssociation,  November  22,  1902, 


VAddlNA  L  aOMPLKIATlONS  AND   INJUIUES  7(j 

these  observers  saw  the  lupus  years  after  the  vaccination  had  been  per- 
formed. Fox  saw  a  case  of  hjpus  begin  in  a  vaccination  scar  shortly 
after  tlie  sore  had  licalcd.  Tl)(M"hild  subsccjucntly  d(;v.(?Iopcd  a  di.sserni- 
nated  hi])ns,  subperiosteal  tuberculous  nodules,  and  jjulnionary  phthisis. 
It  is  higlily  probable  that  this  child  was  already  tuberculous,  as  another 
child  in  the  family  had  previously  died  of  this  disease.  Stelwagon  saw 
a  palm-sized  patch  of  lupus  on  the  arm  in  a  girl  ten  or  twelve  years  after 
a  vaccination  which  was  said  to  have  been  immediately  followed  by 
the  development  of  the  lupus,  the  history  being  given  by  a  physician, 
the  brother  of  the  patient.  All  that  can  be  stated  as  regards  the  rela- 
tionship of  vaccination  to  lupus  is  that  vaccination  may  in  rare  cases 
in  tuberculous  individuals  give  rise  to  a  lupus  at  the  site  of  vaccination. 
That  lupus  should  occasionally  choose  a  vaccination  scar  for  its  seat  is 
no  proof  that  it  was  caused  by  vaccination. 

Vaccination  and  Leprosy.^ — Since  the  general  adoption  of  bovine 
lymph  for  vaccination,  the  question  of  the  invaccination  of  leprosy  has 
resolved  itself  into  one  of  academic  and  retrospective  interest.  It  is 
well,  however,  for  physicians  in  leprous  countries,  if  required  by  unusual 
circumstances  to  employ  humanized  lymph,  to  remember  that  leprosy 
has  probably  in  isolated  instances  been  conveyed  by  vaccination.  Gaird- 
ner,"^  Daubler,^  and  Hillis  have  each  recorded  instances  of  vaccinal 
leprosy,  although  some  doubt  attaches  to  all  of  these  cases. 

Beavan  Rake  and  Buckmaster,  who  have  given  this  matter  much 
study,  believe  "that  the  alleged  cases  of  transmission  of  leprosy  by 
vaccination  are  open  to  serious  doubt."  Hansen,^  of  Bergen,  in  1890, 
made  extensive  inquiry  by  circular  to  all  of  the  physicians  of  Norway 
as  to  the  occurrence  of  vaccination  leprosy.  In  not  a  single  case  was 
there  any  ground  to  suspect  such  an  origin.  This  statement  is  of  espe- 
cial importance  inasmuch  as  there  is  much  leprosy  in  Norway,  and 
vaccination  is  practised  extensively  in  that  country. 

From  experimental  evidence  we  Would  scarcely  expect  leprosy  to  be 
transmissible  by  vaccination.  Inoculation  of  man  and  lower  animals 
has  been  I'epeatedly  attempted  by  Daniellson,  Profeta,  Hansen,  and 
others,  who  inserted  fragments  of  leprous  tissue  and  injected  blood 
from  lepers  beneath  the  skin,  but  with  entirely  negative  results.  There 
is  indeed  no  conclusive  case  on  record  of  the  successful  experimental 
transmission  of  leprosy. 

It  is  true  that  lepra  bacilli  have  occasionally  been  found  in  vaccine 
lymph  in  vesicles  raised  upon  leprous  skin,  but,  as  Beavan  Rake  properly 
states,  no  responsible  person  would  think  of  vaccinating  a  leper  in  an 
affected  part  and  using  such  l^aiiph  for  further  vaccinations. 

Eczema  Following  Vaccination. — Vaccination  may  now  and  then 
induce  the  appearance  of  an  eczema  in  a  child  predisposed  to  the  dis- 
ease, just  as  an  attack  of  measles,  scarlet  fever,  or  simple  teething  may 
act  as  an    exciting  cause.     Eczema  is  an  extremely  common    disease 

'  A  Remarkable  Experience  Concerning  Leprosy,  Briiisb  Nfedical  Journal,  1SS7,  vol.  i.  p.  12C9. 

-  Monatsheft.  f.  prakt.  Derm.,  1SS9,  p.  VIZ. 

■■'  Mentioned  by  Acland,  Allbutt's  System  of  Medicine,  p.  6Jo. 


80  VACCINIA 

among  infants  and  young  children,  and  is  particularly  referable  to 
faulty  feeding  and  digestive  disturbances.  Of  600  cases  of  eczema 
under  the  care  of  Dr.  T.  Colcott  Fox,  249,  or  41.5  per  cent.,  were  seen 
before  the  end  of  the  first  year;  in  40  of  these  eczema  was  known  to  have 
appeared  before  vaccination.  Doubtless  if  these  had  appeared  after 
vaccination,  the  latter  would  have  been  viewed  as  a  probable  etiological 
factor. 

Crocker^  says:  "In  no  case  can  vaccination  be  held  responsible  where 
the  vaccinia  pustule  has  completely  healed  before  eczema  appears." 

Eczematous  children,  if  in  good  health  otherwise,  may  usually  be 
vaccinated  without  any  aggravation  of  the  existing  cutaneous  disease. 
Van  Harlingen^  has  carefully  studied  the  influence  of  vaccination  on 
previously  existing  skin  diseases.  He  writes:  "During  the  smallpox 
epidemic  of  1872  I  observed  all  cases  of  skin  disease  coming  under  my 
notice  in  which  vaccination  had  been  practised.  In  a  few  some  aggrava- 
tion of  the  symptoms  followed ;  in  others  an  apparent  improvement  took 
place.  But  in  the  great  majority  of  cases  vaccination  did  not  appear  to 
exercise  any  influence  whatever  on  the  course  of  the  more  common 
diseases  of  the  skin  coming  under  my  observation."  We  have  from 
time  to  time  vaccinated  persons  with  eczema  and  other  cutaneous  dis- 
eases without  any  injury  whatsoever.  On  the  other  hand,  vaccination 
has  on  a  number  of  occasions  been  followed  by  improvement  and  even 
cure  of  eczemas.  Stelwagon^  says:  "I  have  noted  in  several  instances 
that  amelioration  followed  vaccination,  and  in  one  instance,  in  a  chronic 
case,  a  disappearance  of  the  eczema."  Duhring,  Tait,  and  others  have 
testified  to  the  occasional  curative  influence  of  vaccination  on  eczema. 

While  we  would  not  elect  to  perform  vaccination  upon  a  child  suffer- 
ing from  eczema,  we  should  not  consider  the  latter  condition  a  sufficient 
contraindication  if  smallpox  were  prevalent. 

Bullous  Eruptions  (dermatitis  bullosa;  dermatitis  herpetiforTnis ; 
acute  pemphigus). — In  relatively  rare  instances  vesicobullous  eruptions 
variously  designated  as  pemphigus,  bullous  dermatitis,  and  dermatitis 
herpetiformis  (Duhring's  disease)  have  followed  vaccination.  While 
we  have  no  proof  positive  of  a  causative  relationship  between  vaccinia 
and  these  eruptions,  they  have  now  been  reported  by  careful  observers 
in  a  sufficient  number  of  instances  to  warrant  the  assumption  that  the 
antecedent  vaccination  has  been  of  some  etiological  moment. 

Pusey*  reported  a  case  of  this  character  under  the  title  of  dermatitis 
herpetiformis,  in  which  the  lesions  were  vesicobullous  and  erythema- 
tous, followed  by  pigmentation. 

Dyer^  reported  two  similar  cases  under  the  same  title  after  vaccina- 
tion. One  case  occurred  three  weeks  after  vaccination  and  one  several 
(?)  weeks  thereafter. 

1  Diseases  of  the  Skin,  p.  324. 

2  Remarks  on  Vaccination,  in  Relation  to  Skin  Diseases  and  Eruptions  Following  Vaccination, 
Philadelphia  Medical  Journal,  1902,  p.  184. 

3  Vaccinal  Eruptions,  Journal  of  the  American  Medical  Association,  November  22, 1902. 
■*  Journal  of  Cutaneous  and  Genito-urinary  Diseases,  1897. 

5  St.  Louis  Medical  Gazette,  1898. 


VACCINA  [j  (lOMI'LldATIONS  AND  IS.HHilHS  81 

Bowen*  has  placed  on  record  a  series  of  six  casfs  f)f  l)iil!f>ii,s  dci-rnatitis 
resemblinfij  dermatitis  herpetiformis  following  vaffination.  In  three  of 
the  cases  the  eruption  is  stat(;d  to  iiav(;  made  its  appearance  within  two 
weeks  after  vaccination,  in  one  within  a  week,  while  in  two  it  did  not 
show  itself  until  after  the  lapse  of  a  month.  Corlett  exhibits  two  photo- 
graphs of  postvaccinal  bullous  dermatitis  in  his  work  on  tlie  acute 
infectious  exanthemata.  Stelwagon^  saw  within  one  year  three  cases 
of  bullous  eruption  after  vaccination,  two  of  which  he  regarded  as  acute 
peni'phigus,  and  the  third  as  a  persistent  bullous  erythema  multiforme 
or  dermatitis  herpetiformis.  In  these  cases  the  vaccination  was  what 
is  usually  described  as  a  "good  take,"  but  was  somewhat  slow  in  heal- 
ing, the  crust  remaining  adherent  a  long  time.  The  eruption  appeared 
from  two  to  four  weeks  after  vaccination,  and  had  persisted  at 
the  time  they  were  reported  three,  four,  and  eight  months,  respect- 
ively. 

Sequeira^  showed  to  the  Dermatological  Society  of  T.ondon  in  1902 
a  case  of  'pemphigus  in  a  man  aged  thirty-nine  years,  the  eruption 
appearing  three  weeks  after  a  revaccination.  Three  vaccine  insertions 
were  made,  and  the  first  bleb  is  alleged  to  have  developed  at  the  site  of 
one  of  these.  This  was  followed  in  several  weeks  by  bullre  on  the  arms, 
and  later  on  the  thighs.  Cultures  from  the  early  blebs  were  sterile,  and 
inoculations  of  this  fluid  into  animals  were  negative. 

In  all  of  the  above  cases  save  the  last,  the  patients  were  children 
under  twelve  years  of  age.  The  eruption  usually  appeared  from  two 
to  three  weeks  after  vaccination,  and  in  no  case  after  six  weeks.  In 
most  cases  the  eruption  was  extensive  and  of  long  duration,  with  marked 
tendency  to  relapse.  Some  of  the  cases  were  cured  at  the  end  of  three 
or  six  months,  but  some  persisted  much  longer.  Pusey's  case  continued 
to  have  relapses  for  four  and  a  half  years. 

Rowen  says :  "  The  chief  features  that  these  cases  present  in  common, 
and  that  lead  to  a  conviction  that  they  have  a  common  etiology,  are 
their  occurrence  in  children  after  vaccination;  their  course,  varying 
from  ssveral  months  to  several  years  or  perhaps  longer;  their  urfiformly 
vesicular  and  bullous  character,  with  only  occasional  evidences  of  mul- 
tiformity; the  almost  complete  exemption  of  the  trunk;  the  character- 
istic grouping  about  the  mouth,  nose,  ears,  wrists,  ankles,  and  feet,  and 
the  very  slight  prominence  of  itching  or  other  subjective  symptoms." 
While  most  of  these  cases  run  a  relatively  benign  course,  one  of  the 
writers*  saw  a  fatal  termination  in  a  case  of  bullous  eruption  of  the  acute 
pemphigus  type.  This  occurred  in  a  girl  of  five  years,  the  eruption 
beginning  two  weeks  after  vaccination.  The  writers  have  also  seen 
four  other  cases  of  generalized  bullous  eruption  of  the  t}^e  described 
above,  occurring  shortly  after  vaccination. 

A  remarkable  series  of  bullous  eruptions  occurring  after  vaccination 

1  Journal  of  Cutaneous  and  Genito-uriuary  Diseases,  September,  1901,  p.  401. 
-  Journal  of  the  American  Medical  Association,  November  22, 1902. 
3  British  Dermatological  Journal,  May,  1902,  p.  174. 

*  Schamberg  and  Keech.    A  Case  of  Acute  Fatal  Pemphigus,  Annals  of  Gynecology  and  Pediatries 
February,  1901,  p.  321. 

6 


82  VACCINIA 

is  reported  by'  Howe/  of  Boston.  Ten  cases  are  referred  to,  all  but  one 
occurring  in  persons  who  had  been  recently  vaccinated.  The  skin 
lesions  began  on  an  average  of  five  weeks  after  vaccination;  the  longest 
time  elapsing  between  vaccination  and  the  appearance  of  the  eruption 
was  sixteen  Weeks,  and  the  shortest  period  three  weeks. 

All  of  the  patients  were  adults,  the  ages  varying  from  twenty-one  to 
fifty-two  years.  Six  of  the  ten  cases  proved  fatal;  the  average  duration 
until  recovery  or  death  occurred  was  six  weeks. 

It  will  be  seen  that  these  cases  present  points  of  variation  from  the 
cases  described  by  Bowen.  The  interval  between  vaccination  and  the 
appearance  of  the  eruption  in  Bowen's  cases  was  about  two  and  a  half 
weeks;  in  Howe's  cases  it  was  double  this  period.  Bowen's  cases  occurred 
in  children;  none  of  them  were  fatal,  and  the  trunk  was,  as  a  rule,  free 
of  eruption,  which  was  not  true  in  the  cases  described  by  Howe. 

Howe  was  inclined  to  attribute  the  eruptions  to  infectious  material 
introduced  at  the  time  of  or  after  vaccination.  The  cases  occurred  at 
a  time  when  smallpox  was  prevalent  in  epidemic  form,  and  when  thou- 
sands of  vaccinations  were  being  performed. 

While  these  eruptions,  when  compared  with  the  number  of  vaccina- 
tions performed,  are  extremely  rare,  no  effort  should  be  spared  to  deter- 
mine their  cause  with  a  view  to  their  future  avoidance.  It  is  possible 
that  they  are  manifestations  of  an  extraneous  infection  through  the 
vaccine  wound.  In  this  connection  the  investigations  of  Fernet  and 
Bulloch^  into  the  causation  of  acute  pemphigus  are  of  interest.  These 
writers  report  and  analyze  eight  cases  of  acute  pemphigus  in  butchers; 
six  of  the  cases  proved  fatal  in  from  twenty-four  hours  to  eighteen  days. 
Three  patients  gave  histories  of  wounds  which  continued  to  suppurate 
up  to  the  time  of  the  pemphigus  outbreak.  The  period  of  incubation 
would  appear  to  be  very  long  if  the  disease  arose  from  an  infection,  as 
is  suggested.  In  the  three  cases  referred  to  the  wound  antedated  the 
eruption  three  months,  two  months,  and  five  weeks,  respectively.  Special 
interest  attaches  to  one  case,  in  which  the  patient  is  alleged  to  have 
inoculated  himself  by  contact  with  a  bullous  eruption  on  the  udders 
of  a  coAV. 

Psoriasis. — Psoriasis  is  known  to  have  made  its  first  appearance 
at  the  point  of  vaccination,  and  also  as  a  generalized  outbreak  after 
vaccinia.  No  one,  however,  who  is  at  all  familiar  with  this  disease 
would  look  upon  vaccination  as  a  cause  of  psoriasis.  It  may  simply 
determine  the  time  of  outbreak  in  an  individual  predisposed  to  this 
common  skin  affection;  it  is  quite  possible  that  those  persons  who 
developed  psoriasis  after  vaccination  would  not  have  been  attacked 
with  this  disease  until  a  later  period.  The  occurrence  of  postvaccinal 
outbreaks  of  psoriasis  has  been  noted  by  Klamann,^  1  case;  Camp- 
bell,* 1  case;  Roh€,*  2   acute  general  cases  of   psoriasis  after  vacci- 

1  Cases  of  Bullous  Dermatitis  Following  Vaccination,  Journal  of  Cutaneous  Diseases,  1903,  p.  254. 

2  British  Journal  of  Dermatology,  1896,  pp.  157  and  205. 

3  Jahrbuch  f.  Kinderheilk.,  1879,  Bd.  iv.  p.  371.  ^  Arch.  f.  Derm.,  1877,  p.  311. 
5  Journal  of  Ciitaueous  and  Genito-urinary  Diseases,  1882-83,  p.  11. 


UlSTOLOd  Y  Of  TIIK   Vy\(!(!INK  LESION  8'} 

nation;  Piffard/  1  case;  Wood,^  2  case."?'  Hyde,''  1  ease;  Gaskoin/  5 
cases;  Chain})ard,'''  1  case;  and  Kiohlanc,"  1  case. 

Furunculosis. — (Jropsof  fxjils  have  occasionally  been  observed  dur- 
ing the  course  of  and  following  vaccination.  The  complication  is 
usually  a  trivial  one,  the  furuncles  disappearing  in  a  short  time.  Sinigar^ 
met  v^ith  21  cases  of  furuncles  among  IKK)  vaecinations  in  a  large 
institution,  l^he  boils  develojx'd,  as  a  rule,  late  in  the  course  of  the 
vaccinia.  One  case  appeared  on  the  tenth  day,  1  on  the  sixteenth,  4 
on  the  twenty-second,  1  on  the  twenty-fifth,  2  on  the  twenty-seventh, 

2  on  the  twenty-eighth,  4  on  the  twenty-ninth,  3  on  the  thirtieth,  and 

3  on  the  thirty-fifth  day  after  vaccination.  As  bearing  on  the  cau.se 
of  this  complication,  it  is  interesting  to  note  that  13  of  these  cases 
developed  among  epileptics,  who,  as  Sinigar  remarks,  include  some  of 
the  dirtiest  and  most  troublesome  patients  in  the  asylum. 

HISTOLOGY  OF  THE  VACCINE  LESION. 

But  little  literature  is  available  upon  the  subject  of  the  histological 
changes  in  the  vaccine  pock.  The  following  description  is  condensed 
from  Copeman's'^  presentation  of  the  subject: 

The  vaccine  lesion  passes  through  three  more  or  less  defined  stages 
— namely,  papule,  vesicle,  and  pustule — just  as  does  the  characteristic 
lesion  of  smallpox.  In  both  diseases  the  papule  results  from  inflam- 
matory changes  which  are  most  pronounced  in  the  epithelial  cells  of 
the  mucous  layer  of  the  epidermis.  Through  certain  degenerative 
processes,  the  most  conspicuous  of  which  are  cell  liquefaction  and 
intercellular  oedema,  the  papule  becomes  converted  into  a  vesicle. 

The  vesicle  is  made  up  of  numerous  loculi  or  compartments  which 
are  formed  by  the  spinning  out  of  elongated  epithelial  cells.  The  more 
pronounced  swelling  and  vacuolation  of  the  cells  upon  the  advancing 
edge  of  the  vesicle  leads  to  greater  bulging  upon  the  periphery,  giving 
rise  to  the  umhilication.  The  process  is  identical  in  vaccine  and  vario- 
lous vesicles. 

Kent^  examined  a  series  of  vaccine  vesicles  removed  by  Copeman 
at  various  stages  of  development  from  the  calf.  At  a  quite  early  stage 
an  outpouring  of  leukocytes  occurs  toward  the  site  of  injury.  In  the 
course  of  time  each  bloodvessel  is  surrounded  by  a  mass  of  leukocytes 
which  rapidly  increase  and  convert  the  originally  transparent  fluid  of 
the  vesicle  into  a  purulent  fluid,  thus  giving  rise  to  the  pustule. 

The  rupture  of  the  epithelial  trabecule  or  partitions  converts  the 
multilocular  pock  into  a  unilocular  one.  The  fluid  now  gradually 
becomes  inspissated  and  with  the  necrosed  remains  of  epithelial  cells 
dries  into  a  crust.     Cicatrization  and  healing  go  on  beneath  the  crust; 

1  Journal  of  Cutaneous  and  Geuito-urinary  Diseases,  1882-S3,  p.  119. 

2  Ibid.,  p.  161.  3  itid.,  p.  14. 
*  On  Psoriasis  or  Lepra,  1875,  p.  49. 

5  Annales  de  derm.,  1895,  p.  498.  «  Ibid.,  p.  880. 

^  Vaccinal  Complications,  Lancet,  1902.  s  Loc.  cit.,  p.  73. 

9  Britisb  Medical  Journal,  1894,  vol.  ii.  p.  633.    Quoted  by  Copeman. 


84  VACCINIA 

the  depth  of  the  resulting  scar  depends  upon  the  extent  of  destruction 
of  the  true  skin. 

The  minute  histological  changes  in  the  vaccine  lesion  have  been 
studied  by  Gustav  Mann,^  for  whom  Copeman  excised  lesions  at  differ- 
ent stages  of  development  from  the  calf. 

In  a  specimen  removed  within  an  hour  after  vaccination  the  wound 
is  blocked  by  a  clot  which  externally  is  of  a  coarse,  granular  nature,  and 
between  the  edges  of  the  epidermis  finely  granular.  The  bloodvessels 
close  to  the  injury  are  dilated  and  many  completely  thrombosed  with 
leukocytes.  Red  corpuscles  may  be  seen  adhering  to  the  lumen  of 
the  capillaries  and  arteries. 

The  nuclei  of  both  the  epidermal  and  dermal  cells  are  swollen  and 
the  basophile  chromatin  contained  in  them  is  doubly  increased.  In  the 
dermis  an  infiltration  of  leukocytes  into  the  loose  connective  tissue  is 
visible. 

At  the  end  of  twenty-four  hours  the  epithelium  close  to  the  injury  has 
increased  twofold  or  threefold  in  thickness  and  a  characteristic  phenom- 
enon is  already  noticed,  namely,  the  formation  of  Guarnieri's  supposed 
parasites.  The  nuclear  and  nucleolar  chromatin  is  increased  and  a 
considerable  portion  of  the  latter  leaves  the  nucleus  and  is  found  lying 
free  in  the  cytoplasm.  The  granules  may  fuse  and  give  rise  to  more 
or  less  solid  spheres  lying  alongside  of  the  nucleus  or  even  indenting  it. 

From  the  twenty-fourth  to  the  forty-eighth  hour  the  dermis  shows 
a  gradually  increasing  oedema,  associated  with  an  emigration  of  leuko- 
cytes. As  a  result  of  the  oedematous  condition  the  lymph  is  prevented 
from  escaping  downward  by  the  dense  elastic  layer  of  the  dermis  and 
the  thick  fibrous  bundles  of  the  hypoderm.  Toward  the  periphery 
the  lymph  channels  are  blocked  by  leukocytes,  and  there  is  left  but 
one  path  for  the  lymph,  namely,  through  the  basal  membrane  and 
then  through  the  spaces  between  the  epithelial  cells.  These  lymph 
spaces  are  distended  by  the  fluid,  which  becomes  limited  by  the  dense 
and  resistant  horny  layer. 

At  the  end  of  three  days  three  zones  may  be  distinguished.  Farther 
away  from  the  line  of  inoculation  the  only  noticeable  change  is  a  dilata- 
tion of  the  interepithelial  lymph  channels.  All  of  the  cells  immediately 
within  this  region,  save  the  horny  cells,  are  swollen  and  contain  granules 
like  those  in  the  granular  layer,  thus  indicating  a  premature  aging  of 
the  cells. 

The  dermis  beneath  fonns  large  bullae,  the  walls  of  which  are  made 
up  of  compressed  connective-tissue  cells  and  leukocytes.  No  wander- 
ing cells  are  seen  in  the  blebs,  but  fairly  numerous  bacilli  singly  and 
in  pairs. 

Still  nearer  the  point  of  inoculation  the  epithelial  cells  show  enlarged 
nuclei,  which  undergo  fragmentation  into  six  or  twelve  smaller  nuclei. 
Concurrently  with  the  formation  of  these  multinucleated  giant  cells 
there  are  seen  greatly  distended  lymph  vesicles  in  the  epithehum,  the 

1  Quoted  by  Copeman,  loc.  cit. 


lIlSTOLOdY  OF  Till':  VA(J(;[NI<:  LESION  85 

walls  of  which  are  made  up  of  stretched  and  degenerated  ej;iUirli;il 
cells.  The  vesicles  contain  a  fibrin  reticuluin  and  vaiions  rnifMo-organ- 
isms. 

Internal  to  the  zone  just  described  the  giant  cells  are  re[>iaced  by 
cells  but  a  fifth  to  a  quarter  of  their  size,  and  containing  but  one  or  two 
nuclei,  which  appear  to  be  derived  from  the  multinucleated  giant  cells. 
The  centre  of  the  vaccinated  area  shows  no  living  epithelial  fells,  but 
merely  the  remains  of  the  horny  layer  and  a  dense,  dri(;d  blood  chjt. 

The  above  changes  hold  good  for  the  fifth  day,  the  only  diH'erence 
being  an  increase  in  size  of  the  central  necrosed  area  and  a  lateral 
spreading  of  the  zone  of  infection. 

The  increased  infiltration  of  leukocytes  causes  the  central  area  to 
necrose  more  and  more,  the  connective-tissue  elements  succu]id)ing  to 
the  pressure  exerted  by  the  wandering  cells. 

The  hypoderm  shows,  especially  about  the  fifth  day,  a  considerable 
swelling  of  the  thick,  white,  fibrous  bundles  called  forth  by  the  great 
activity  of  the  fixed  connective- tissue  cells. 

Copeman  considers  the  most  characteristic  feature  of  vaccination  to 
be  the  appearance,  immediately  outside  the  necrosed  area  in  the  super- 
ficial, loose  dermal  tissue,  of  a  number  of  globular  masses,  varying  in  size 
and  arranged  singly  or  in  pairs,  and  which  are  colored  by  a  special 
staining  process.     At  the  spreading  edge,  very  short  bacilli  are  seen. 

It  is  suggested  that  the  large  globules  represent  either  a  capsulated, 
sporulated,  or  involuted  stage  of  the  bacillus  which  Copeman  elsewhere 
intimates  may  be  the  specific  microbe  of  the  disease. 

Much  that  pertains  to  the  bacteriology  of  vaccinia  will  be  found  in 
the  chapter  on  the  pathology  of  variola. 

Tyzzer^  made  a  careful  experimental  study  of  vaccination  and  vario- 
lation lesions  in  animals,  particularly  with  reference  to  the  presence  of 
Guarnieri's  bodies.  He  successfully  inoculated  the  corneas  of  twenty- 
five  rabbits  with  vaccine  lymph,  and  the  corneas  of  twenty  rabbits  with 
variolous  lymph.  In  addition  a  number  of  calves  were  vaccinated, 
some  upon  the  cornea  and  others  upon  different  parts  of  the  cutaneous 
and  mucous  surfaces. 

He  interprets  the  cycle  of  development  of  the  c}i;orrhyctes  variola;  in 
vaccinia  as  follows: 

Injection:  Epithelial  cells  are  invaded  by  small  forms  in  which  it 
is  difficult  to  distinguish  structure.  These  small  forms  are  found  between 
cells  and  in  various  parts  of  the  cytoplasm,  but  after  their  entrance  into 
the  cell  they  take  a  position  near  the  nucleus.  Groivth :  After  becoming 
located  near  the  nucleus  they  become  larger,  and  with  tliis  growth  the 
character  of  their  structure  becomes  apparent.  They  then  consist  of  a 
reticular  protoplasm  in  which  is  a  clear  spot  containing  a  mass  of  basic 
staining  material.  Although  it  is  impossible  to  distinguish  a  nuclear 
membrane  bounding  this  clear  spot,  it  seems  probable  that  this  clear 
spot  with  the  granule  in  it  is  the  chromatin  of  the  organism.     The 

1  The  Etiology  and  Pathology  of  Vaccinia,  Journal  of  Medical  Research.  February,  1904. 


86  VACCINIA 

organism  is  situated  n  a  space  in  the  cell,  generally  many  times  its 
own  volume.  This  space  is  usually  continuous  with  or  is  a  part  of  the 
perinuclear  space.  Division  of  the  Nuclear  Material:  Certain  forms, 
in  which  the  chromatin  mass  is  irregular,  precede  those  in  which  the 
chromatin  is  divided.  In  the  latter  the  chromatin  granules  may  be  few 
or  numerous.  The  chromatin  granules  later  take  a  peripheral  position, 
where  they  then  form  the  centres  of  minute  masses  which  bulge  from  the 
surface.  Multiplication :  These  small  masses,  becoming  free,  are  found 
in  the  space  occupied  by  the  segmenting  form  and  in  the  cytoplasm  of 
the  same  cell.  They  constitute  the  small  forms  described  as  the  first 
of  the  series.  They  now  scatter  and  penetrate  neighboring  cells.  The 
invasion  of  the  surrounding  normal  cells  by  the  small  forms  resulting 
from  this  multiplicative  process  constitutes  autoinfection,  and  by  it 
the  process  extends.  The  immediate  effect  of  the  parasite  is  to  cause 
an  increase  in  size  of  the  epithelial  cells.  This  increase  in  cell  volume 
is  accompanied  in  the  corneal  lesion  by  proliferation.  The'  exudation 
which  usually  accompanies  the  lesions  is  secondary  to  the  degeneration 
of  the  epithelium.  Tyzzer  states  that  he  is  "fully  convinced  that  the 
vaccine  body  is  an  organism  and  represents  the  etiological  agent  in  this 
disease." 

THE  BLOOD  IN  VACCINIA. 

There  is  a  constant  leukocytosis  during  vaccination,  the  leukocytosis 
appearing  in  two  waves,  according  to  Sobotka.^  The  primary  one 
(varying  from  12,000  to  23,000)  is  observed  from  the  third  to  the  seventh 
day,  and  a  secondary  wave  (10,000  to  17,500)  from  the  tenth  to  the 
twelfth  day. 

Billings^  states  that,  no  changes  are  exerted  upon  the  haemoglobin 
or  red  cells  by  vaccination,  but  a  definite  leukocytosis  is  produced. 
The  counts  average  about  15,000  leukocytes  per  cubic  millimetre. 
The  maximum  of  the  leukocytosis  is  reached  during  the  height  of  pus- 
tulation  of  the  vaccine  lesion,  after  which  a  gradual  diminution  in  the 
white  cells  takes  place. 

1  Zeitschr.  f.  Heilk.,  1893,  Bd.  xiv.  p.  349. 

2  Medical  News,  lh98,  vol.  Ixxiii.  p.  301. 


CHAPTER    11. 

THE  RELATIONSHIP  OF  COWPOX  OR  VACCINIA  TO  SMALLPOX. 

It  has  taken  almost  a  century  of  experiiiKsntution  to  prove  the  truth 
of  the  statements,  made  by  Jenner  in  his  first  publication,  that  smallpox 
and  cowpox  were  modifications  of  the  same  disease.  What  a  tribute 
to  the  intuitive  discernment  of  this  great  man! 

The  experiments  which  have  led  to  the  general  (although  not  univer- 
sal) acceptance  of  this  view  have  been  in  the  direction  of  the  conversion 
of  smallpox  into  vaccine  by  variolation  of  the  cow.  It  is  impossible  to 
produce  in  the  cow  a  generalized  eruption  similar  to  the  smallpox  erup- 
tion in  man;  it  is,  moreover,  impossible  to  intensify  the  virulence  of, 
cowpox  and  convert  it  into  smallpox,  but  it  is  possible  to  convert  the 
virus  of  human  smallpox  into  vaccine  virus  by  passage  through  the 
bovine  species. 

The  English  Royal  Commission  on  Vaccination  presents  in  its  official 
report  (1898)  a  valuable  review  of  this  subject,  from  which  we  freely 
abstract. 

Most  of  the  endeavors  to  transfer  smallpox  from  man  to  the  bovine 
species  have  been  unattended  with  success,  and  have  usually  been  with- 
out any  definite  result.  This  has  been  true  not  only  in  attempts  to 
produce  the  disease  by  infection  through  the  respiratory  and  digestive 
tract,  but  also  in  many  instances  by  direct  inoculation.  Most  of  the 
inoculation  experiments  may  be  grouped  in  three  categories. 

The  first  class  includes  experiments  in  which  inoculation  of  smallpox 
matter  into  the  cow  produced  a  vesicle  identical  with  or  closely  resem- 
bling the  vesicle  produced  by  vaccine  inoculation.  If  a  typical  vesicle 
was  not  produced  at  the  first  inoculation,  the  transference  of  the  mate- 
rial from  the  first  vesicle  would  in  a  second  or  third  remove  in  the  cow 
give  a  typical  vesicle  capable  of  producing  in  man  results  indistinguish- 
able from  ordinary  vaccination.  Such  experiments  were  carried  out 
by  Thiele  (1838),'Ceeley  (1840),  Badcock  (between  1840  and  1860), 
Voigt  (1881),  Haccius  and  Eternod  (1890),  King  (1891),  Simpson  (1892), 
and  Hime  (1892). 

In  the  second  category  belong  the  experiments  performed  by  Klein 
and  Copeman.  Klein,  who  in  1879  had  apparently  failed  in  thirty-one 
attempts,  subsequently  found,  in  1892,  that  the  result  of  the  first  inocu- 
lation in  the  cow  of  smallpox  matter  was  not  a  distinct  vesicle,  but 
merely  a  thickening  and  redness  of  the  wound.  Lymph  pressed  from 
the  thickened  wound  produced,  when  inoculated  into  a  second  animal, 
a  similar  but  more  pronounced  result.  In  the  third  and  fourth  cow 
the   reddening   and   thickening  were   still   greater.      L^^Bph   squeezed 


88      RELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 

from  the  wounds  of  the  fourth  cow  produced  typical  vaccinia  in  a  child, 
and  the  crust  from  the  child  when  reinoculated  into  the  cow  produced 
similar  vaccine  vesicles.  Copeman  obtained  results  of  a  similar  char- 
acter, and  succeeded  in  the  third  remove  in  the  cow  in  producing  a 
reaction  which  showed  commencing  vesiculation. 

In  the  third  class  may  be  placed  the  results  obtained  in  an  elaborate 
investigation  conducted  by  a  commission  of  the  Society  of  Medical 
Sciences  of  Lyons,  under  the  direction  of  Chauveau  (1865).  Their 
results  may  be  briefly  summarized  as  follows: 

Inoculation  of  the  cow  with  smallpox  matter  in  any  one  of  the  thirty 
animals  experimented  upon  did  not  give  rise  to  a  vaccine  vesicle.  Never- 
theless a  definite  result  was  obtained  in  the  form,  not  of  a  vesicle,  but 
of  a  thickening  and  inflammation  of  the  wound;  when  a  puncture  was 
made  this  became  a  papule.  Lymph  squeezed  from  such  a  papule  and 
inserted  into  a  second  animal  gave  rise  to  a  like  papule;  and  this,  again, 
might  be  used  for  a  third  animal,  but  often  failed;  and  the  effect  could 
in  no  case  be  carried  through  more  than  three  or  four  removes.  When 
the  inoculation  was  repeated  on  an  animal  in  which  a  previous  inocula- 
tion had  produced  such  a  papule,  no  distinct  papule  was  formed,  and, 
moreover,  lymph  squeezed  from  the  seat  of  inoculation  produced  no 
effect  at  all  when  used  for  subsequent  inoculation  of  another  animal. 

Thus  Chauveau  and  his  commission  found  that  smallpox  implanted 
in  the  cow  gave  rise  to  a  specific  effect  which  was  not  cowpox,  but  was 
of  the  nature  of  smallpox,  though  its  manifestations  in  the  cow  were 
different  from  those  of  smallpox  in  man.  Lymph  from  the  lesions  in 
the  first  cow  was  capable  of  producing  smallpox  in  the  human  subject. 

It  is  evident  from  the  above  experiments  that  the  results  obtained 
from  attempted  variolation  of  the  cow  have  exhibited  marked  varia- 
bility. The  vast  majority  of  the  inoculations  have  been  of  a  negative 
character.  These,  however,  do  not  invalidate  the  positive  results 
which  have  now  attained  a  very  considerable  number,  and  which  have 
been  reported  by  careful  and  trustworthy  investigators  at  different 
times  and  in  different  countries. 

When  reaction  does  result  from  the  insertion  of  variolous  material 
into  the  cow,  the  local  effects  vary  somewhat.  There  may  be  directly 
produced  a  typical  vaccine  vesicle,  or,  as  occurs  in  most  instances,  a 
papule  or  inflammatory  induration  which  on  further  inoculation  yields 
a  vaccine  vesicle.  We  are  thus  forced  to  the  conclusion  that  smallpox 
_^s  converted  into  cowpox  by  passage  through  the  tissues  of  the  bovine 
species.  The  transformation  is  at  times  sudden  and  complet&._at  other^ 
__times^gradual  and  incomplete,  and  sometimes  fails  altogether^__  The 
circumstances  wliichTavor  such' a  are  but  little  unHer stood, 

although  it  would  appear  that  the  youth  of  the  inoculated  animal  is  a 
factor.  The  best  results  have  been  obtained  with  calves  not  overjjiree 
or  four  months  old.     "  ~~ — ^ 

It  is  claimed  that  it  is  possible  for  cows  to  develop  cowpox  through 
inhalation  of  the  contagium  of  variola.  In  this  connection  it  is  inter- 
esting to  refer  to  an  occurrence  noted  by  Ceely  in  1840.    This  writer 


BELATIONSmr  OF  f/OWPOX  on   VAC'C'/NFA    TO  SMALLPOX     HU 

states  that  he  observed  cowpox  develoj)  in  five;  out  of  eight  milch  cows 
twelve  to  fourteen  days  after  they  were  seen  li<.'king  some  floek  from  a 
mattress  upon  which  a  jjatiejit  died  of  eonfliuMit  smallj)OX,  and  which 
had  been  spread  upon  the  ground  to  be  aired.  (Jareful  investigation 
revealed  the  fact  that  the  animals,  which  had  been  on  the  farm  for 
considerable  time,  were  in  good  health  before  their  admission  to  the 
pasture  where  the  exposed  bedding  lay.  There  had  not  been  any  cow- 
pox  in  the  neighborhood.  That  the  cowpox  may  have  resultcfl  hom  a 
volatile  contagium  derived  from  the  smallpox-infected  bedding  is  not 
improbable,  in  view  of  the  simultaneous  sickening  of  the  cows  after  a 
period  of  incubation  of  about  two  weeks.  The  possibility  of  infection 
through  the  digestive  tract,  which  Chauveau  and  others  have  shown 
may  take  place,  must  not  be  entirely  ehminated  in  seeking  the  explana- 
tion of  the  manner  in  which  the  disease  was  received. 

That  the  transformation  of  the  smallpox  into  the  vaccine  virus  is 
frequently  a  gradual  process  which  is  not  completed  in  the  first  bovine 
inoculation  has  been  on  more  than  one  occasion  unfortunately  proven 
by  the  transference  of  true  smallpox  to  persons  who  were  vaccinated 
with  material  taken  from  the  first  cow. 

In  1836  J.  C.  Martin,  of  Attleborough,  Massachusetts,  inserted  into 
the  udder  of  a  cow  lymph  taken  from  a  smallpox  lesion  upon  the  body 
of  a  man  who  died  of  variola.  Subsequently  matter  derived  from  the 
cow  was  inserted  into  the  arm  of  about  fifty  persons.  Nearly  all  of 
these  individuals  developed  smallpox  in  the  due  course  of  time,  and 
three  of  the  number  died.  The  disaster  so  preyed  upon  the  mind  of 
the  unfortunate  physician  that  he  became  insane. 

A  similar  occurrence  has  been  reported  by  Dr.  Thomas  F.  Wood.^ 
We  quote  his  own  words:  "I  had  occasion  just  after  the  war  (1865- 
66),  while  in  charge  of  the  Wilmington  Smallpox  Hospital  during  an 
epidemic  of  the  disease,  to  go  over  the  same  ground  of  attempting  the 
production  of  artificial  cowpox.  It  happened,  during  the  progress  of 
the  experiment  that  an  army  medical  inspector,  whose  name  I  have 
forgotten,  was  making  a  tour  of  the  hospitals;  hearing  of  my  experi- 
ments, he  visited  my  hospital  and  after  examination  pronounced  the 
small  vesicles  genuine  cowpox,  and  confirmed  his  faith  in  his  opinion 
by  making  some  inoculations  on  the  arms  of  two  children  in  an  Irish 
family  near  by.  The  inoculations  resulted  in  a  genuine  smallpox, 
which  went  through  the  family  in  various  grades  of  intensity." 

Other  instances  of  a  similar  character  have  been  recorded.  That 
such  infections  are  not  the  result  of  inoculation  with  the  unchanged 
variolous  material  originally  introduced  into  the  cow  is  evidenced  by 
the  fact  that  smallpox  has  been  conveyed  to  the  human  subject  from 
a  papule  of  the  second  remove.     (Lyons  Commission.) 

These  deplorable  accidents  have  directed  attention  to  the  unwisdom 
of  using  material  of  the  first  or  second  bovine  generation,  and  empha- 
size the  importance  of  passing  the  variolous  virus  through  four  or  five 
or  more  animals  before  employing  it  upon  man. 

1  Chicago  liledical  Journal  and'Examiner,  October,  ISSl. 


90      RELATIONSHIP  OF  GOWPOX  ORIVACCINIA  TO  SMALLPOX 

The  demonstration  of  the  fact  that  vaccine  virus  may  be  produced 
from  a  variolous  source  is  of  great  importance.  It  is  readily  seen  that 
an  epidemic  of  smallpox  occurring  in  some  inaccessible  country,  w^here 
active  vaccine  lymph  could  not  be  obtained,  could  be  made  to  supply 
the  material  for  its  own  suppression. 

The  proof  of  the  common  ancestry  of  vaccinia  and  variola  refutes 
the  theoretical  arguments  advanced  by  Crookshank  and  others  against 
the  protective  influence  of  vaccination.  These  writers  have  attempted 
to  fortify  their  belief  in  the  inefiicacy  of  vaccination  by  assuming  the 
duality  of  these  two  affections,  the  opinion  being  maintained  that  an 
attack  of  disease  could  only  afford  protection  against  the  same  disease. 
The  premise  being  false,  the  entire  inference  falls  to  the  ground. 

Modern  bacteriological  research  strongly  supports  the  empiric  dis- 
covery of  Jenner.  Pasteur  and  others  have  shown  that  it  is  quite  possi- 
ble, by  the  use  of  an  attenuated  virus,  to  produce  a  mild  attack  of  an 
infectious  disease  and  thus  protect  against  a  more  severe  type  of  the 
same  infection. 

That  vaccinia  and  variola  are  in  essence  the  same  disease  is  scarcely 
to  be  doubted.  The  passage  of  smallpox  matter  through  the  compara- 
tively insusceptible  tissues  of  the  bovine  species  attenuates  the  virus 
to  such  an  extent  that  it  is  permanently  robbed  of  the  virulence  which 
it  once  possessed.  Instead  of  producing  a  dangerous  and  contagious 
disease,  it  gives  rise  to  an  innocent  affection  capable  of  transmission 
only  by  inoculation,  and  having  the  beneficent  property  of  protecting 
against  the  original  disease  which  gave  it  birth.  Shakespeare  might 
well  have  had  vaccination  in  mind  when  he  wrote: 

"  Take  thou  some  new  infection  to  thine  eye, 
And  the  rank  poison  of  the  old  will  die." 

Jenner  was  strongly  impressed  with  the  fact  that  smallpox  and  cow- 
pox  were  one  and  the  same  disease.  Baron  quotes  the  following  notes 
which  were  left  by  Jenner  in  one  of  his  journals: 

"The  origin  of  the  smallpox  is  the  same  as  that  of  the  cowpox;  and 
as  the  latter  was  probably  coeval  with  the  brute  creation,  the  former 
was  only  a  variety  springing  from  it."  Cowpox  and  smallpox  are  "not 
hona  fide  dissimilar  in  their  nature ;  but,  on  the  contrary,  identical.  On 
this  ground  I  gave  my  first  book  the  title  of  *  An  Inquiry  into  the  Causes 
and  Effects  of  the  Variolm  Vaccinae' — a  circumstance  which  has  been 
since  regarded  by  many  as  the  happy  foresight  of  a  connection  which 
was  destined  by  further  evidence  to  become  more  warranted." 

From  the  above  it  will  also  be  seen  that  Jenner  regarded  cowpox 
as  the  progenitor  of  human  smallpox.  This  belief  he  reiterated  on  a 
number  of  occasions.  It  will  be  remembered  that  in  the  beginning  of 
the  "Inquiry"  he  says:  "This  fluid  (from  the  grease)  seems  capable  of 
generating  a  disease  in  the  human  body  (after  it  has  undergone  the 
modification  I  shall  presently  speak  of — viz.,  transmission  through  the 
cow)  which  bears  so  strong  a  resemblance  to  smallpox  that  I  think  it 
highly  probable  that  it  may  be  the  source  of  that  disease."    Again,  in  a 


NAT!/ HAL  SOUnaiCH  OF  LYMPH  91 

letter  to  l)e  Carro  in  IS()3  he  remarks:  "1  am  happy  to  find  an  ojjinif^n 
taken  up  by  in(!  <\,m\  nicntionc^l  in  my  first  [)ubli('jition  hu.s  so  able  a 
supporter  as  yours(!lf.  I  thought  it  highly  probal^lc  tliat  tlic  smallpox 
might  be  a  mahgnant  variety  of  the  cowpox,  but  this  idc-a  was  scouted 
by  my  countrymen,  particularly  P.  (Pearson)  and  W.  (VVoodville)." 

'  Whether  smallpox  is  a  cowpox  of  exalted  virulence  or  cowpox  an 
attenuated  smallpox  remains  apparently  unsolvable.  Copeman  is 
inclined  to  support  the  view  championed  by  Jenner.  He  says:^  "The 
artificially  inoculated  form  of  cowpox  which  we  term  vaccinia  is  noth- 
ing more  nor  less  than  variola  modified  by  transmission  through  the 
bovine  animal.  Perhaps  the  most  reasonable  inter[)retation  of  such 
results  may  be  that  smallpox  and  vaccinia  are  both  of  them  descended 
from  a  common  stock — from  an  ancestor,  for  instance,  which  res(;m- 
bled  vaccinia  far  more  than  it  resembled  smallpox.  It  is  conceivable, 
indeed,  that  the  seeming  vaccinia,  obtained  in  the  calf  by  inoculation 
of  smallpox  matter  into  that  animal,  may  after  all  be  but  a  reversion 
to  an  antecedent  type." 

The  Various  Natural  Sources  of  Lymph. — During  the  investigation 
of  the  casual  cowpox,  Jenner  conceived  the  idea  of  propagating  the  dis- 
ease by  inoculation  after  the  manner  of  the  smallpox,  first  from  the 
cow,  and  finally  from  one  human  being  to  another.  The  first  vaccina- 
tion was  performed  in  1796  upon  a  lad  by  the  name  of  James  Phipps, 
the  virus  being  taken  from  the  hand  of  Sarah  Nelmes,  a  dairymaid 
who  had  been  accidentally  infected  with  the  cowpox.  Notwithstanding 
the  resemblance  of  the  vesicle  produced  to  that  obtained  by  variolous 
inoculation,  Jenner  could  scarcely  believe  that  the  patient  was  secure 
from  the  smallpox.  He  was,  however,  inoculated  with  smallpox  virus 
some  months  afterward  and  on  numerous  occasions  subsequently,  but 
each  time  without  result. 

In  1798  Jenner  again  came  into  possession  of  virus  from  the  cow 
and  made  arrangements  for  a  series  of  inoculations.  "A  number  of 
children,"  he  says,  "were  inoculated  in  succession,  one  from  the  other; 
and  after  several  months  had  elapsed  they  were  exposed  to  the  infection 
of  smallpox,  some  by  inoculation,  others  by  variolous  effiuvia,  and 
some  in  both  ways,  but  they  all  resisted  it." 

This  strain  of  lymph  was  suffered  to  die  out  and  none  was  found 
until  Woodville,  in  1799,  discovered  a  case  of  natural  cowpox  in  Gray's 
Inn  Lane.  With  this  lymph  he  vaccinated  seven  persons,  and  likewise 
certain  others  from  the  hand  of  a  dairj^maid  who  had  contracted  cow- 
pox  from  one  of  the  cows  at  this  place.  This  virus  was  successively 
passed  through  hundreds  of  persons  and  became  known  as  "Wood- 
ville's  lymph." 

Dr.  Pearson  also  discovered  a  case  of  cowpox  in  a  dairy  at  ]Maryle- 
bone  Road,  although  some  of  the  lymph  which  he  sent  out  was  probably 
obtained  from  Woodville's  cases.  Woodville  and  Pearson  both  dis- 
tributed the  lymph  widely,  and  supplied  it  to  many  of  the  continental 

1  Vaccination,  Loudon,  1899,  p.  64. 


92      RELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 

cities.  Although  Jenner  himself  used  some  of  Woodville's  lymph,  he 
later  found  another  source  of  supply  in  the  dairy  of  Mr.  Clark,  in  Kentish 
Town. 

Dr.  Waterhouse,  of  Boston,  secured  some  of  Jenner's  lymph  through 
Dr.  Haygarth,  of  Bath,  who  obtained  it  from  Mr.  Greaser.  De  Carro 
of  Vienna,  Stromeyer  of  Hanover,  and  others  also  obtained  some  of 
the  Jennerian  stock. 

At  this  time  other  instances  of  natural  cowpox  became  known.  Sacco, 
a  faithful  disciple  of  Jenner,  discovered  a  case  of  cowpox  on  the  plains 
of  Lombardy  in  1800.  A  strain  of  lymph  was  developed  from  this, 
some  of  which  was  sent  to  De  Carro,  at  Vienna.  This  enthusiastic 
vaccinator  forwarded  a  supply  to  Constantinople,  and  subsequently 
other  lymph  of  Italian  origin  to  India;  the  latter  virus  was  of  equine 
ancestry,  having  been  developed  by  Sacco  from  a  case  of  accidental 
horsepox  in  a  coachman. 

Natural  cowpox  is  said  to  have  been  found  in  Naples  in  1812,  and 
in  Piedmont  in  1830.  Macerdoni  discovered  it  in  cows  of  Swiss  breed 
in  Rome  in  1832  and  1834,  and  in  the  latter  year  a  lymph  stock  was 
established.  Cowpox  occurred  in  Wiirtemberg  in  1802,  and  in  1812 
Bremer  observed  it  in  Berlin.  Fischer  saw  a  case  near  Luneberg,  and 
Mende  noted  one  in  Greifswalde.  Giesker,  Luders,  Ritter,  Riss,  and 
Albers  encountered  cases  in  various  portions  of  Germany.  Numann 
says  that  in  Holland  cowpox  was  seen  in  1805,  1811,  and  1824. 

An  epizootic  of  this  disease  among  cows  is  said  to  have  occurred  in 
Russia  in  1838,  in  a  small  village  near  St.  Petersburg. 

In  France  cowpox  was  first  observed  in  1810  in  the  department  of 
La  Meurthe;  in  1822  it  was  found  in  Clairvieux.  In  the  next  half-cen- 
tury it  was  discovered  some  score  or  more  times  in  different  parts  of 
the  country. 

A  famous  strain  of  lymph  was  derived  by  Bousquet  in  1836  from  a 
case  of  cowpox  at  Passy,  in  the  environs  of  Paris.  The  disease  occurred 
upon  the  hand  of  a  dairymaid,  from  whom  Bousquet  vaccinated  a  number 
of  children.  In  the  second  and  subsequent  removes,  the  virus  proved 
itself  much  superior  to  the  lymph  which  had  then  been  long  in  use. 
Bousquet  in  a  painstaking  memoir  accurately  compared  the  course  of 
the  old  and  the  new  lymph.  These  results  were  confirmed  by  Bruchir, 
of  Versailles,  and  by  Steinbrenner,  who  worked  with  Mrs.  Pass's  lymph 
in  1840,  and  compared  it  with  virus  obtained  from  other  sources  in 
1841  and  1845.  Similar  results  were  obtained  by  Estlin,  of  Bristol,  in 
1838  with  lymph  derived  from  a  Gloucestershire  farm. 

Don  F.  Xavier  Balmes,  director  of  the  Spanish  Vaccine  Expedition, 
discovered  cases  of  natural  cowpox  in  the  Peruvian  Andes  and  in  other 
regions  of  South  America. 

Ceely,  in  1841,  stated  that  he  had  experimented  with  lymph  from  more 
than  fifteen  sources,  six  of  which  represented  cases  of  natural  cowpox. 

In  1866  a  milch  cow  with  cowpox  was  discovered  at  Beaugency, 
France.  A  valuable  strain  of  lymph  was  developed  from  this  case  by 
Professor  Depaid.     It  was  from  this  source  that  Martin,  of  Boston, 


ANIMAL   VA(H!INATr()N  93 

obtained  lymph  with  which  he  inaugurated  animal  vaccination  in 
America  in  1870.  It  may  be  worth  while  to  state  the  great  probability 
that  in  America  only  has  th(^  "stock"  of  the  Beaugency  virus  been 
perpetuated. 

The  strain  of  lymph  now  used  by  the  English  Government  Animal 
Vaccine  Establishment  was  derived  in  1881  from  a  case  of  cowpox  at 
Tvaforet,  near  Bordeaux. 

In  1881  Martin,  of  Boston,  observed  a  case  of  spontaneous  cowpox 
at  Cohasset,  a  small  town  in  Massachusetts.  The  Cohasset  and 
the  Beaugency  stocks  were  for  a  while  propagated  separately  in  this 
country,  but  subsequently  became  mixed. 

Fischer  and  Voigt  in  Germany,  Haccius  in  Switzerland,  King  in 
India,  and  others  have  of  late  years  propagated  cowpox  virus  by  vario- 
lating heifers,  producing  thus  what  has  been  called  variola-vaccine 
lymph. 

We  are  conscious  of  a  reassuring  sense  of  security  in  the  knowledge 
that  reliable  vaccine  lymph  can  be  produced  by  the  inoculation  of  vario- 
lous material  into  a  succession  of  bovine  animals,  for  if  existing  strains 
of  lymph  are  lost  or  become  too  much  attenuated,  we  have  at  hand  a 
means  of  replenishing  the  prophylactic  virus. 

Animal  Vaccination.— By  the  term  animal  vaccination  is  meant  the 
propagation  of  lymph  through  successive  series  of  calves  or  heifers, 
the  original  virus  being  derived  ah  initio  from  a  case  of  spontaneous 
cowpox.  Martin^  says  the  term  can  and  has  been  applied  to:  1.  Vac- 
cination casually  or  intentionally  from  the  original  spontaneously  occur- 
ring disease  in  the  milch  cow.  2.  Retrovaccination  with  virus  obtained 
from  the  vaccine  disease  in  the  human  subject.  3.  From  vesicles,  said 
to  be  vaccine  vesicles,  obtained  by  variolation  of  kine,  or  the  inocula- 
tion of  bovine  animals  with  the  virus  of  smallpox.  4.  The  method  of 
true  animal  vaccination,  or  the  inoculation  of  a  bovine  animal  with  the 
virus  of  original  spontaneous  cowpox;  from  this  another,  and  so  on  in 
continuous  and  endless  series  as  a  source  of  vaccine  virus. 

In  1810  a  Neapolitan  physician,  Galbiati  by  name,  published  an 
article  advocating  animal  vaccination.  He  had  employed  this  method 
for  some  seven  years,  believing  that  it  ensured  greater  vigor  and  purity 
of  the  lymph.  Galbiati  seems  to  have  espoused  this  procedure  because 
of  the  occasional  transmission  of  syphilis  by  arm-to-arm  vaccination. 
The  method  was  at  first  extremely  unpopular,  and  its  author,  abused 
and  ridiculed,  is  said  to  have  become  insane  and  to  have  ended  his  life 
by  suicide.  His  disciple  and  successor,  Negri  (to  whom  Ballard  gives 
credit  for  the  origin  and  introduction  of  animal  vaccination),  continued 
the  propagation  of  lymph  from  animal  to  animal,  and  successfully 
brought  the  practice  into  general  favor.  The  l}Tiiph  wliich  he  employed 
at  first  (in  1842)  appears  to  have  been  of  human  origin,  but  subsequently 
he  obtained  material  from  a  case  of  natural  co'u^ox  in  Calabria.  Palas- 
ciano,  a  townsman  of  Negri  and  a  strong'advocate  of  animal  vaccina- 

1  Report  on  Animal  Vaccination,  read  before  the  American  Medical  Association,  1S77.    We  are 
indebted  for  much  of  the  information  conveyed  in  this  chapter  to  this  admirable  report. 


94       RELATIONSHIP  OF  COWPOX  OB   VACCINIA   TO  SMALLPOX 

tion,  disseminated  knowledge  on  this  subject  throughout  Europe,  by 
an  address  before  the  Medical  Congress  of  Lyons.  A  young  French 
physician,  Lanoix,  one  of  those  present,  became  greatly  interested  in 
the  subject  and  subsequently  went  to  Naples  to  study  animal  vaccina- 
tion under  Negri.  In  1864  he  returned  to  Paris  with  a  heifer  which 
had  been  vaccinated  at  Naples.  Chauveau  and  Diday  were  permitted 
to  take  some  lymph  from  this  animal  at  the  Lyons  railway  station. 
Lanoix  proceeded  to  Paris  and  in  company  with  Chambon  established 
a  private  institution  for  the  propagation  of  animal  lymph.  The  new 
practice  excited  considerable  interest,  and  the  Academy  of  Medicine, 
encouraged  by  a  government  appropriation,  appointed  a  commission 
with  Professor  Depaul  at  its  head  to  investigate  the  subject.  The  report 
was  favorable  to  animal  vaccination,  although  some  dissentient  opinions 
were  expressed.  About  this  time  natural  cowpox  was  discovered  at 
Beaugency,  and  Depaul  had  an  opportunity  of  employing  lymph  from 
this  source.  It  is  said  that  this  lymph  stock  was  lost  during  the  siege  of 
Paris  in  the  Franco-Prussian  War,  and  that  the  only  extant  derivative 
from  this  source  is  that  sent  to  America. 

From  Paris  the  practice  of  animal  vaccination  spread  to  Belgium 
through  the  efforts  of  Warlomont,  who  obtained  some  Neopolitan 
lymph  from  Lanoix.  He  later,  in  1868,  discovered  a  case  of  spontaneous 
cowpox  at  Esneux  (Liege). 

Through  private  enterprise  animal  vaccine  establishments  were 
organized  in  the  various  European  capitals.  The  commercial  spirit 
rendered  a  real  service  to  humanitarian  science. 

Pissin  opened  up  such  an  animal  vaccine  institution  in  Berlin,  and 
Vienna  soon  had  a  similarly  equipped  establishment.  Haccius  in 
1882  founded  the  "Institute  Vaccinale  Suisse,"  which  received  a  cer- 
tain recognition  at  the  hands  of  the  Swiss  government.  Paris  now  has 
an  "Institut  de  Vaccine  Animale,"  which  under  the  direction  of  Cham- 
bon and  St.  Yves  Menard,  supplies  the  municipality  with  all  the  lymph 
required  for  public  vaccinations. 

In  Germany  all  or  nearly  all  of  the  vaccine  establishments  are  under 
governmental  control  and  supervision. 

England  in  1881  authorized  the  founding  of  the  Government  Animal 
Vaccine  Establishment  in  Lamb's  Conduit  Street,  and  the  use  of  animal 
lymph  has  now  practically  superseded  arm-to-arm  vaccination. 

To  Dr.  H.  A.  Martin,  of  Boston,  belongs  the  credit  of  introducing 
animal  vaccination  into  the  United  States.  In  1870  he  sent  a  special 
agent  to  France,  who  returned  with  an  abundant  supply  of  Beaugency 
lymph.  Having  secured  a  herd  of  young,  healthy  animals,  he  at  once 
began  the  propagation  of  animal  lymph.  He  and  his  son  subsequently 
discovered  a  case  of  spontaneous  cowpox  in  Cohasset,  Massachusetts. 

Advantages  of  Animal  Vaccination. — The  use  of  calf-transmitted 
lymph  has  certain  advantages  over  long  humanized  virus;  these  maybe 
stated  as  follows: 

1.  Animal  vaccination  produces  a  vaccinia  which  approaches  more 
nearly  the  Jennerian  prototype,  and  reaches  therefore  a  greater  degree 


ADVANTAfJICS  OF  AN/AfAL    VA(!<J[NATI(>N  95 

of  perfection  than  that  produced  by  long  liunianizcd  virus.  The  cow- 
pox  casually  produced  on  the  hands  of  dairymaids  was  believed  by 
Jenner  to  confer  full  and  cotn])lete  protection  against  smallpox.  The 
bovine  species  ap[)ears  to  be;  the  natural  soil  of  the  j)roj)hylacti(;  pock, 
and  the  view  is  maintained  by  numy  that  l)ovine  lymph,  or  that  fJerived 
from  an  early  human  remove,  creates  a  more  complete  and  more  lasting 
immunity.  The  inferiority  of  humanized  virus  is  doubtless  due  to  a 
weakening  or  degeneration  of  the  lymph  product  as  a  result  of  the  long- 
continued  transmission  through  the  human  subject.  Jenner  really 
anticipated  such  a  deterioration  in  the  quality  of  vaccine  lymph  from 
this  cause.  Copeman  says  that  "in  the  present  state  of  our  knowledge, 
however,  such  enfeeblement  of  the  specific  virus  can  hardly  be  regarded 
as  probable,  except. under  conditions  that  may  be  obviated  by  reasona- 
ble skill  and  care  on  the  part  of  the  operator.  Jenner  early  discovered 
that  vaccine  lymph  only  exhibited  its  full  degree  of  activity  when  taken 
at  the  stage  of  maturation  of  the  vesicle,  and  before  its  contents  became 
at  all  purulent.  If  this  precaution  be  observed,  together  with  strict 
cleanliness  in  the  removal  and  insertion  of  the  lymph,  experience  has 
shown  that  no  appreciable  degeneration  can  be  demonstrated." 

2.  The  use  of  animal  lymph  precludes  the  possibility  of  transmitting 
by  vaccination  diseases  peculiar  to  the  human  species.  One  of  the  most 
weighty  reasons  that  led  to  the  adoption  of  animal  vaccination  and  to  its 
preference  over  arm-to-arm  transmission  was  the  recognition  of  the 
possibility  of  inducing  syphilis  by  vaccine  inoculation.  No  matter 
how  rare  such  an  accident  might  be,  the  remotest  liability  of  such  an 
occurrence  constitutes  a  serious  argument  against  the  use  of  humanized 
lymph.  The  bovine  species  being  totally  insusceptible  to  syphilis,  l^-mph 
derived  from  this  source  is  incapable  of  transmitting  such  infection. 

Erysipelas  appears  to  be  a  much  rarer  complication  of  vaccinia 
since  the  general  employment  of  animal  l}Tnph.  It  is  probable  that 
many  cases  of  vaccinal  erysipelas  in  the  past  were  due  to  secondary 
infection  of  the  vesicle  at  the  time  that  it  was  punctured  to  withdraw 
lymph  for  further  inoculations.  The  almost  universal  use  of  animal 
lymph  removes  the  necessity  of  tapping  the  vaccine  vesicle,  thus  ren- 
dering erysipelas  from  this  cause  practically  non-existent.  Again,  many 
cases  of  erysipelas  were  doubtless  the  result  of  the  emplo}aiient  of 
crusts  which  had  not  been  wisely  selected  or  properly  preserved.  "\Miat- 
ever  the  cause  or  causes  may  have  been,  actual  experience  shows  an 
enormous  reduction  in  the  relative  and  aggregate  incidence  of  this  com- 
plication since  vaccination  w^ith  humanized  lymph  has  fallen  into 
desuetude. 

There  is  little  or  no  danger  of  transmitting  tuberculosis  in  bovine 
lymph,  inasmuch  as,  in  addition  to  the  diagnostic  use  of  tuberculin,  all 
calves  are  killed  and  carefully  examined  in  well-regulated  establish- 
ments before  the  virus  is  sent  out;  furthermore,  it  has  been  sho-um  that 
the  admixture  of  glycerin  to  the  l>Tnph  is  capable  of  destropng  the 
life  of  any  tubercle  bacilli  that  may  be  present. 

3.  Animal  vaccination  offers  an  almost  inexhaustible  supply  of  vac- 


96      RELATIONSHIP  OF  COWPOX  OR  VACCINIA  TO  SMALLPOX 

cine  lymph,  for  the  number  of  calves  yielding  the  same  can  be  multi- 
plied at  will.  During  extensive  epidemics  of  smallpox,  v^hen  human 
vaccine  was  employed,  the  community  was  often  placed  in  an  embarrass- 
ing and  dangerous  predicament  owing  to  an  insufficient  supply  of 
vaccine  material.  During  the  great  pandemic  of  smallpox  from  1870 
to  1873,  a  veritable  vaccine  famine  existed  in  many  countries.  All 
sorts  of  vaccinifers  were  drawn  upon,  and  much  worthless  lymph  derived 
from  spurious  and  irregular  cases  was  employed,  of  course,  with  entirely 
unsatisfactory  results. 

4.  Animal  lymph  appears  to  give  a  much  larger  percentage  of  suc- 
cessful revaccinations  than  long  humanized  virus.  Martin  says:  "The 
number  of  those  who,  in  revaccination  with  the  old,  long  humanized 
virus  (not  that  of  early  human  removes)  experience  vaccinal  effect  may  be 
stated  at  the  outside  at  35  per  cent.  The  number  of  those  revaccinated 
with  equal  care  and  repetition  with  animal  virus  and  virus  of  very 
early  human  removes,  I  affirm  to  be  a  fraction  over  80  per  cent. — a  differ- 
ence of  45  per  cent. ;  and  this  45  per  cent.  I  firmly  believe  to  approxi- 
mately represent  the  number  of  those  insensible  to  the  enfeebled  influ- 
ence of  long  humanized  virus,  but  sensible  to  the  intense  contagium 
of  variola  just  in  the  same  degree  as  sensible  to  the  intense  power  of 
bovine  virus  and  that  of  the  early  human  removes  from  it." 

Comparison  of  the  Course  of  Vaccinia  Produced  by  Original  Cow- 
pox  Virus,  Long  Humanized  Virus,  and  Calf-transmitted  Virus,  Re- 
spectively. Original  Cowpox  Virus. — ^The  vaccine  disease  produced  by 
virus  from  a  case  of  original  cowpox  or  from  early  human  removes 
therefrom  lasts  from  twenty-one  to  thirty-two  days,  counting  from  the 
insertion  of  the  lymph  to  the  falling  of  the  crust.  At  the  end  of  the 
third  or  beginning  of  the  fourth  day  papulation  occurs;  vesiculation 
takes  place  at  the  end  of  the  fifth  day,  but  the  vesicle  continues  to  grow 
until  the  decline  of  the  areola  or  even  a  few  days  after  this.  The  vesicle 
has  a  pearly  or  slightly  bluish  tint;  it  really  resembles,  as  Jenner  re- 
marked, "a  section  of  a  pearl  on  a  rose-leaf."  The  areola  appears  first 
about  the  end  of  the  ninth  or  beginning  of  the  tenth  day  and  persists 
until  the  twelfth,  thirteenth,  or  fourteenth  day.  Desiccation  and  forma- 
tion of  the  crust  are  not  complete  before  the  sixteenth  or  seventeenth 
day;  the  crust  is  never  spontaneously  detached  before  the  twenty-first 
day  and  usually  not  before  the  twenty-fifth  to  the  twenty-eighth  day. 
Occasionally  it  will  remain  upon  the  vaccine  site  until  the  thirtieth  or 
thirty-second  day.  The  crust  is  round,  thick,  umbilicated,  and  of  a 
rich  brown  or  mahogany  tint. 

A  very  decided  febrile  reaction  attends  the  rise,  development,  and 
decline  of  the  areola.  This  febrile  disturbance  was  considered  to  be  of 
great  importance  by  the  early  vaccinators,  especially  Jenner,  who 
regarded  it  as  a  sine  qua  non  of  vaccinal  impression  upon  the  system, 
and  an  indelible  characteristic  cicatrix  remains  after  the  termination 
of  the  disease.  In  the  early  days  it  was  not  at  all  rare  for  the  vesicle 
to  break  down  and  ulcerate,  leading  to  a  spreading  and  troublesome 
loss  of  tissue  and  occasionally  to  erysipelatous  infection. 


COURSE  OF   VA(J(JJNIA    WITH  D/FFFJU'JNT  LVM/'J/S  f)7 

Long  Humanized  Virus. — ^The  most  distirif^uisliirif^  characteristic  of 
the  vaccinia  produced  l)y  lonf^  huinanizcd  virus  is  the  f)revitv  of  the 
course  of  the  disease.  The  duration  varies  very  much  with  different 
lymph  stocks.  With  a  virus  used  by  Martin  and  obtained  from  Ceely, 
the  course  of  the  disease  from  the  time  of  insertion  of  the  lymph  to  the 
spontaneous  detachment  of  the  crust  was  l)ut  eleven  days;  whereas 
with  a  lymph  of  French  origin  employed  by  Martin,  th(!  crust  came  off 
from  the  twenty-first  to  the  twenty-sixth  day.  Lymph  from  the  National 
Vaccine  Institution  of  Great  Britain  ran  a  course  of  fourteen  days  to 
the  falling  of  the  crust.  These  various  "stocks,"  although  propagated 
for  years,  preserved  their  distinctive  durations.  It  was  even  found, 
when  two  different  lymphs  were  inserted — one  on  one  arm  and  the 
second  on  the  other — that  each  strain  retained  its  special  features. 

In  brief,  it  may  be  stated  that  long  humanized  lymph  produces  a 
vaccinia  of  shorter  duration  and  milder  intensity  than  original  and 
early  virus.  With  the  lymph  which  induced  a  vaccinia  of  eleven  days' 
duration,  the  areola  was  formed  on  the  seventh  day  and  sometimes  on 
the  sixth.  The  Jennerian  "stock"  of  the  British  Vaccine  Institution 
induced  a  vaccina  of  fourteen  days'  duration,  the  areola  developing  on 
the  seventh  or  eighth  day. 

The  crust  derived  from  vaccination  with  long  humanized  lymph 
is  very  small,  thin,  and  often  devoid  of  umbilication.  The  febrile  reac- 
tion accompanying  such  a  vaccinia  is  slight  or  absent,  even  when  many 
insertions  are  made. 

Calf-transmitted  Virus. — As  would  be  expected  the  vaccinia  resulting 
from  the  employment  of  calf-transmitted  lymph  closely  resembles  the 
disease  induced  by  early  human  removes  from  original  cowpox,  such 
as  were  observed  by  Jenner.  With  the  animal-transmitted  virus,  how- 
ever, the  reaction  is  not  so  violently  inflammatory  as  that  which  occurred 
with  original  cowpox  lymph.  Ceely,  in  1840,  stated  his  belief  that  the 
tendency  to  undesirable  intensity  in  the  original  cowpox  is  tempered 
by  successive  transmissions  through  young  animals.  He  inoculated  a 
series  of  eleven  calves  and  found  that  the  objectionable  qualities  of  the 
lymph,  as  determined  by  human  vaccinations,  w-ere  gradually  but  pro- 
gressively eliminated.  The  animal  virus  now  used  usually  runs  its 
course  from  twenty-one  to  thirty  days. 

Glycerinated  Lymph. — To  S.  Monckton  Copeman^  belongs  the 
credit  of  advocating  the  addition  of  glycerin  as  a  vaccine  purifier,  and 
of  establishing  the  employment  of  glycerinated  l}'mph  upon  a  scientific 
basis.  Glycerin  had  previously  been  used  for  the  purpose  of  increasing 
the  volume  of  the  lymph  and  also  as  a  Ivmph  preservative. 

As  far  back  as  March,  1850,  Mr.  R.  Cheyne-  advocated  (in  a  letter 
appearing  in  the  Medical  Times)  the  use  of  fluid  hmph  to  which  some 
glycerin  had   been  added  as  superior  to  the  dry  points.      In  1853  he 

1  We  desire  to  acknowledge  our  indebtedness  for  much  of  the  material  presented  in  this  chapter 
to  the  admirable  book  of  S.  Monckton  Copeman  (Vaccination,  its  Natural  History  and  Pathology, 
London,  1899),  which  we  have  freely  consulted. 

*  Copeman  appears  to  have  been  unaware  of  Cheyne's  work  until  a  few  years  ago. 

7 


98       RELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 

demonstrated  to  the  presidents  of  the  Royal  Colleges  of  Physicians 
and  Surgeons  a  child  whom  he  had  successfully  vaccinated  with  glycer- 
inated  lymph  prepared  six  months  previously.  Cheyne  admitted  that 
he  was  indebted  for  knowledge  of  this  procedure  to  the  previous  publi- 
cations of  Mr.  J.  Startin  on  the  therapeutic  uses  of  glycerin. 

Miiller,  of  Berlin,  further  demonstrated  the  fact  that  vaccine  lymph 
could  be  considerably  increased  in  quantity  by  the  admixture  of  glyc- 
erin without  interfering  with  its  specific  activity.  He  proved  that  the 
lymph  might  be  diluted  with  three  times  its  bulk  of  glycerin  without 
in  any  way  lessening  its  potency.  It  is  evident  that  Miiller's  chief 
object  was  to  increase  the  quantity  of  available  l}Tiiph,  a  matter  of 
much  importance  during  smallpox  epidemics,  particularly  when  there 
was  danger  of  a  vaccine  famine. 

With  the  same  object  in  view  Dr.  Stephen  Mackenzie,  of  the  London 
Hospital,  during  the  great  smallpox  epidemic  in  1870-71,  added  glyc- 
erin to  lymph  in  order  to  increase  the  amount  just  before  conducting  a 
large  series  of  vaccinations. 

Dr.  Warlomont,  of  Brussels,  in  1882  placed  upon  the  market,  under 
English  patent,  a  method  of  admixture  of  glycerin  with  vaccine  lymph, 
but  no  mention  was  made  of  the  contained  glycerin  until  some  years 
later. 

Copeman,  in  a  paper  presented  to  the  International  Congress  of 
Hygiene,  held  in  London  in  1891,  advocated  the  addition  of  glycerin 
to  vaccine  lymph  for  the  purpose  of  purifying  and  preserving  it.  The 
method  consisted  in  the  "intimate  admixture  of  a  given  amount  of 
lymph,  or  rather  vesicle  pulp,  with  a  sterilized  50  per  cent,  solution 
of  chemically  pure  glycerin  in  distilled  water,  and  in  subsequent  storage 
of  the  resultant  emulsion  in  sealed  capillary  tubes  for  several  weeks." 

Copeman  had  previously  endeavored  by  diverse  means  to  inhibit 
the  growth  in  vaccine  material  of  the  various  extraneous  organisms, 
and  if  possible  destroy  them  without  weakening  the  specific  activity 
of  the  lymph.  These  measures  failing,  he  resorted  to  the  addition  of 
glycerin. 

Previous  to  Copeman's  experiments  there  had  been  no  appreciation 
of  the  influence  of  the  glycerin  as  a  bacteriological  purifier  of  lymph 
when  the  mixture  is  stored  for  some  time  and  protected  from  the  access 
of  light  and  air. 

When  a  glycerin  emulsion  of  vaccine  is  prepared  in  the  manner 
indicated  by  Copeman,  an  inhibition  and  later  destruction  of  the  foreign 
aerobic  bacteria  is  brought  about.  The  purification  is  a  gradual  one, 
as  can  be  determined  by  making  plate  cultures  of  the  lymph  from  time 
to  time,  and  estimating  the  number  of  colonies  of  organisms  present. 

Since  the  publication  of  Copeman's  paper  in  1891,  other  careful 
observers  have  fully  substantiated  the  claims  of  this  investigator. 
Chambon  and  Menard,  in  1892,  were  not  only  able  to  purify  and  pre- 
serve lymph  by  glycerin  admixture,  but  they  claim  to  have  produced 
an  improvement  in  the  activity  of  lymph  which  in  its  fresh  state  had 
given  only  mediocre  results.    Such  a  lymph  produced  after  fifteen  days' 


(iLYCERINATKI)  LYMI'll  99 

admixture  with  glycerin  a  |)assal)le  vesiele,  aiul  ;ifl,(;i-  forty,  fifty,  or 
sixty  days  a  typical  one.  The  improvcnnent  in  pot(!ncy  was  attrihuted 
by  them  to  the  gradual  destruction  of  foreign  bacteria  in  the  fluid. 
Professor  Straus,  who  made  plate  cultures  of  this  lymph,  achieved 
results  identical  with  those  obtained  by  Copeman,  although  the  work 
was  done  prior  to  the  publication  of  ("of)ernan's  article.  Fresh  glyceiin- 
ated  lymph  gave  rise  to  numerous  colonies  of  various  organisms,  espe- 
cially the  staphylococcus  pyogenes  aureus  and  staphylococcus  albus, 
but  when  stored  for  fifty  to  sixty  days  plate  cultures  proved  to  be 
absolutely  sterile  as  regards  these  extraneous  bacteria.  These  experi- 
ments were  repeated  many  times,  but  always  with  the  same  result. 

Leoni,  in  a  paper  read  before  the  International  Medical  Congress, 
held  in  Rome  in  1894,  concludes  that  (1)  recently  collected  vaccine 
is  a  contaminated  vaccine,  containing  numerous  foreign  germs,  some 
of  which  are  capable  of  exerting  pathogenic  properties  when  inoculated 
into  the  system;  (2)  the  contaminating  organisms  become  extinguished 
in  vaccine  preserved  for  a  certain  period  in  glycerin;  (3)  vaccine  pre- 
served in  glycerin  from  one  to  four  months  after  it  is  collected  is  the 
type  of  fure  vaccine,  with  an  exclusively  specific  virulence;  (4)  this  is 
the  quality  of  vaccine  with  which  the  hygienist  of  to-day  should  con- 
cern himself  in  the  prophylaxis  of  variola. 

Klein  has  added  the  weight  of  his  testimony  as  to  the  purifying  influ- 
ence of  glycerin  on  vaccine  lymph.  In  stating  his  belief  that  the  specific 
organism  of  variola  is  probably  a  spore-bearing  bacillus,  he  incidentally 
remarks:  "  ....  it  is  established  that  the  active  principle  of 
vaccine  is  preserved  in  glycerin,  although,  as  is  also  known,  glycerin 
is  a  germicide  for  cocci  and  sporeless  bacilli." 

In  1896  the  German  government  appointed  a  commission  presided 
over  by  Schmidtmann,  and  including  Koch,  Pfeiffer,  and  Frosch, 
together  with  the  Directors  of  the  Vaccine  Institutes  of  Berlin,  Cologne, 
and  Stettin,  to  investigate  into  the  best  methods  for  the  collection, 
preservation,  storage,  distribution,  and  use  of  vaccine  lymph.  The 
report  stated  that  fresh  lymph  contained  numerous  bacteria  which 
diminish  progressively  under  the  influence  of  the  glycerin  admixture. 
Streptococci  and  diphtheria  organisms  added  to  the  hinph  were  killed 
in  eleven  days  and  twenty  days,  respectively.  These  experimenters, 
as  well  as  Kitasato,  in  Japan,  determined  that  glycerin  w^ith  distilled 
water  could  be  added  to  the  extent  of  from  fifteen  to  twenty  times  the 
weight  of  vesicle  pulp  without  destroying  the  vaccine  principle. 

Copeman  and  Blaxall  have  shown  that  not  only  are  the  ordinary 
foreign  bacteria  of  fresh  lymph  destroyed  by  glycerinization,  but  that 
pathogenic  organisms  such  as  those  of  tuberculosis  and  erysipelas,  when 
added  in  large  number  for  experimental  purposes,  also  perish. 

The  fact  that  the  tubercle  bacillus  thrives  particularly  well  upon  agar 
containing  6  per  cent,  of  glycerin  does  not  invalidate  the  claim  that 
this  agent  in  a  strength  of  40  to  50  per  cent,  is  a  valuable  microbicide. 
Indeed,  Copeman  and  Blaxall  and  likewise  Klein  have  proven  that 
tubercle  bacilli  cannot  be  recovered  after  exposure  for  a  month  to  the 


100    RELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 

action  of  glycerin,  present  to  the  extent  of  about  40  per  cent.,  either 
in  a  culture  in  sterile  bouillon  or  in  fresh  vaccine  material.  These 
investigators  have  furthermore  shown  that  an  emulsion  of  glycerinated 
lymph  inoculated  with  active  tubercle  bacilli,  and  allowed  to  stand  for 
a  month,  was  incapable  of  producing  tuberculosis  in  guinea-pigs,  whereas 
the  contaminated  vaccine  lymph  without  the  glycerin  added  invariably 
produced  this  disease. 

Rosenau^  (1903),  in  a  study  of  the  germicidal  action  of  glycerin, 
concluded  that  it  has  distinct  but  very  feeble  germicidal  and  antiseptic 
properties. 

Small  quantities  of  glycerin,  less  than  10  per  cent.,  added  to  nutrient 
media,  have  well-known  powers  of  favoring  the  growth  and  multiplica- 
tion of  many  forms  of  bacteria. 

The  presence  of  50  per  cent,  of  glycerin  will  restrain  all  bacterial 
growth.  No  growth  or  multiplication  of  bacteria  takes  place  in  nutrient 
media  containing  32  per  cent,  of  glycerin,  but  moulds  grow  in  stronger 
percentages,  viz.,  40  to  49  per  cent. 

In  order  to  prevent  the  growth  and  development  of  pus  cocci,  at  least 
33  per  cent,  of  glycerin  must  be  present. 

The  germicidal  action  of  glycerin  is  probably  due  to  its  affinity  for 
water,  causing  a  dehydration  of  the  bacteria. 

Glycerin  ordinarily  destroys  the  micrococci  of  suppuration,  whether 
the^e  be  in  pure  culture  or  in  the  pus  itself,  within  two  weeks.  This 
action  varies  according  to  the  temperature.  Pus  cocci  may  live  in 
glycerin  for  months  in  the  ice-chest,  whereas  at  the  body  temperature 
they  die  in  a  week. 

Glycerin  has  a  selective  influence  upon  the  diphtheria  bacillus,  which 
succumbs  much  more  quickly  than  most  other  organisms. 

The  bacteria  of  the  typhoid  and  colon  group  often  show  a  marked 
resistance  to  the  effects  of  glycerin  in  strong  proportions. 

Glycerin  in  all  strengths  has  practically  no  effect  upon  endogenous 
spores.  Anthrax  spores  were  kept  alive  and  virulent  two  hundred  days 
in  the  strongest  percentages  of  glycerin,  and  at  warm  temperatures. 

Tetanus  spores  in  pure  culture,  freed  of  all  organic  matter  and  washed 
free  of  toxin,  may  lose  their  virulence  in  glycerin  in  thirty  days  at  the 
body  temperature,  but  they  live  for  months  (one  hundred  and  eighty 
days)  at  room  temperature  or  in  the  ice-chest.  Glycerin,  therefore, 
cannot  be  depended  upon  to  purify  vaccine  or  other  organic  matter 
containing  this  contamination.  The  virulence  of  the  spores  is  lost 
long  before  they  actually  die,  for  they  still  retain  the  power  of  growing 
and  multiplying  if  placed  under  favorable  conditions. 

Under  these  circumstances,  therefore,  they  also  regain  their  original 
pathogenoid  properties.  Glycerin  has  practically  no  effect  on  diph- 
theria toxin. 

At  a  meeting  of  the  British  Medical  Association  in  1896,  Copeman 
and  Blaxall  presented  a  paper  on  "  The  Influence  of  Glycerin  upon  the 

1  Director  of  the  Hygienic  Laboratory,  United  States  Public  Health  and  Marine  Hospital  Service, 
Bulletin  16, 1903. 


GLYCERIN  ATI:  I)  LYAff'lf  101 

Growth  of  liacteria."  The  bacteria  employed  in  the  experimentations 
comprised  staphylococcus  pyogenes  aureus,  staphylococcus  pyogenes 
albus,  streptococcus  pyogenes,  baf;illus  pyocyuneus,  hafillus  subtilis, 
bacillus  coli  communis,  bacillus  diphtherite,  and  bacillus  tuberculosis. 
Smallpox  and  vaccine  material  in  the  form  of  "crusts"  and  lymph 
were  also  employed. 

"Results:  1.  No  visible  development  of  the  micro-organisms  em- 
ployed took  place  in  the  presence  of  more  than  30  per  cent,  of  glycerin. 

"2.  None  of  the  micro-organisms  experimented  with  could  be  recov- 
ered after  exposure  for  a  month  to  the  action  of  from  30  to  40  per  cent, 
glycerin,  with  the  exception  of  bacillus  coli  communis  and  bacillus 
subtilis  when  kept  in  the  cold. 

"3.  Bacillus  coli  communis,  unlike  bacillus  typhosus,  resists  the 
action  of  50  per  cent,  glycerin  in  the  cold  for  a  considerable  period — a 
fact  likely  to  prove  of  value  as  an  addition  to  our  present  methods  of 
differentiating  these  microbes  one  from  another. 

"4.  The  samples  of  smallpox  and  vaccine  material,  whether  as 
'crusts'  or  lymph,  were  sterihzed  completely,  so  far  as  extraneous 
microbes  were  concerned,  in  a  week,  by  the  presence  of  glycerin  to 
the  extent  of  about  40  per  cent,  in  the  broth  tubes.  This  short  period 
of  resistance  is,  doubtless,  in  part  to  be  explained  by  the  fact  that  the 
smallpox  crusts  used  in  these  experiments  had  been  obtained  several 
months  beforehand.  Presumably,  therefore,  the  number  of  microbes 
which  had  been  able  to  survive  for  so  long  a  period  the  process  of  dry- 
ing would  be  much  less  than  might  be  expected  to  be  present  in  *  crusts' 
recently  obtained." 

Copeman  sets  forth  the  advantages  of  glycerinated  lymph  in  the 
following  terms: 

"1.  By  employing  the  method  of  glycerination  of  lymph  pulp,  great 
increase  in  quantity  can  be  obtained  without  any  consequent  deteriora- 
tion in  quality,  the  percentage  of  insertion  success  following  on  its  use 
being  equal  to  that  obtained  with  perfectly  active  fresh  lymph. 

"2.  Glycerinated  lymph  does  not  dry  up  rapidly  as  does  unglycerin- 
ated  lymph,  thus  simplifying  the  process  of  vaccination. 

"3.  Glycerinated  lymph  does  not  coagulate;  so  that  it  never  becomes 
necessary  to  discard  a  tube  on  this  account. 

"4.  Glycerinated  lymph  can  be  produced  absolutely  free  from  the 
various  streptococci  and  staphylococci  which  are  usually  to  be  found  in 
untreated  calf  lymph,  and  which  are,  under  certain  circumstances, 
liable  to  occasion  suppuration. 

"5.  In  like  manner  the  streptococcus  of  erysipelas,  in  the  event  of 
its  having  been  originally  present  in  the  IjTnph  material,  is  rapidly 
killed  out  by  the  germicidal  action  of  the  glycerin. 

"6.  The  tubercle  bacillus  is  effectually  destroyed  even  when  large 
quantities  of  virulent  cultures  have  been  purposely  added  to  the  Ijinph. 

"7.  The  possibility  of  inoculation  of  sj^hilis  is  eliminated,  as  the 
calf  is  not  subject  to  this  disease. 

"  8.  The  necessity  for  collecting  children  together,  with  the  attendant 


102    BELATIONSRIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 

risk  of  spread  of  infectious  diseases,  or  of  transporting  a  calf  from  place 
to  place,  is  obviated,  while  the  danger  of  'late'  erysipelas  in  the  child 
is  diminished  by  reason  of  there  being  no  necessity  to  open  the  mature 
vesicles  for  the  purpose  of  obtaining  lymph. 

"9.  The  bacteriological  purity  and  clinical  activity  of  large  quantities 
of  the  lymph  can  be  readily  tested  prior  to  distribution. 

"  10.  By  reason  of  the  possibility  of  keeping  large  stocks  of  glycer- 
inated  lymph  on  hand  for  considerable  periods  of  time  v^^ithout  appre- 
ciable deterioration,  any  sudden  demand,  such  as  is  likely  to  arise  on 
the  outbreak  of  epidemic  smallpox,  can  be  promptly  met. 

"11.  The  expense  of  producing  glycerinated  lymph  is  proportionately 
small,  since  the  amount  obtainable  from  each  calf  is  enormously  in- 
creased." 

Rosenau^  made  a  study  of  the  bacteriological  impurities  of  vaccine 
virus  as  it  occurs  in  commercial  preparations  upon  the  market  in  the 
United  States.  The  virus  of  ten  different  vaccine  propagators  was 
examined  during  a  period  of  more  than  a  year.  Of  190  dry  points 
examined,  an  average  of  4354  bacteria  per  point  was  found.  A  number 
of  the  points  contained  over  15,000  and  one  as  high  as  44,000  organisms. 

Of  244  tubes  of  glycerinated  virus  examined,  an  average  of  1742 
bacteria  per  tube  was  found.  A  number  of  the  capillary  tubes  con- 
tained over  10,000  bacteria,  and  one  as  high  as  30,000.  This  evidenced 
lack  of  care  in  the  preparation  of  the  lymph. 

Pus  cocci,  pathogenic  for  laboratory  animals,  were  found  both  in 
dry  points  and  the  glycerinated  virus.  Much  of  the  virus  above  referred 
to  was  "green" — i.  e.,  it  had  not  been  glycerinated  for  a  sufficient 
period. 

During  the  winter  of  1901-02  the  glycerinated  virus  contained  an 
average  of  4698  bacteria  per  tube.  In  the  spring  of  1902  the  average 
fell  to  1058  bacteria  per  tube.  In  the  winter  of  1 902,  89  tubes  examined 
gave  an  average  of  29  bacteria  per  tube;  the  maximum  was  239. 

Glycerinated  virus  when  properly  prepared  is  freer  from  impurities 
than  dry  points  made  with  fresh  lymph. 

There  is  practically  no  difference  between  the  glycerinated  virus 
dried  upon  ivory  points  and  that  hermetically  sealed  in  capillary  tubes, 
so  far  as  bacteriological  impurities  are  concerned. 

Tetanus  spores  may  live  a  long  time  in  vaccine  virus;  they  remained 
alive  and  virulent  on  dry  points  after  two  hundred  and  ninety-five  days, 
and  in  glycerinated  virus  sealed  in  capillary  tubes  three  hundred  and 
fifty  days. 

Rosenau  was  unable  to  find  tetanus  germs  or  spores  in  any  of  the 
considerable  number  of  glycerinated  points  and  tubes  examined  with 
this  object  in  view.  He  states  that  tetanus  organisms  cannot  grow  or 
produce  their  toxin  either  in  glycerinated  virus  or  on  the  dry  points. 
"It  would  take  gross  carelessness  to  contaminate  the  vaccine  with  a 
sufficient  number  of  tetanus  spores  to  carry  the  disease  to  those  vac- 
cinated." 

i  Loc  cit.,  Bulletin  12,  1903. 


QLYGEBINATED  LYMPH  103 

The  writer  concludes  that  the  excessive  irDpuriti(;s  found  in  some  of 
the  glycerinated  virus  upon  the  market  is  largely  due  to  the  overcon- 
fidence  in  the  germicidal  value  of  glycerin. 

Vaccine  propagators  become  careless,  ti-usting  to  the  glycerin  to 
purify  the  product.  Glycerin  is  too  feehh;  a  germicide  to  purify  vaccine 
matter  which  has  a  great  initial  contamination. 

The  virus  is  also  at  times  put  upon  the  market  with  undue  haste 
when  an  unusual  demand  exists. 

Howard'  found  actinomyces  in  virus  from  five  vaccine  establishments 
twenty-four  times  in  a  total  of  ninety-five  cultures.  Nine  difi'erent 
species  of  actinomyces  were  found,  of  which  six  appeared  to  be  pre- 
viously undescribed.  The  organisms  are  supposed  to  reach  the  virus 
from  the  air,  water,  soil,  hay,  straw,  and  hide. 

The  writer  thinks  it  is  not  improbable  that  some  of  the  postvaccinal 
suppuration  infections  are  caused  by  these  organisms  and  are  cases  of 
atypical  actinomycosis. 

Sabrazis,  and  Jolly  and  FoUi,  also  found  actinomyces  in  vaccine  virus. 

The  Preparation  of  Glycerinated  Calf  Lymph  (Copeman). — "The  method 
best  adapted  for  the  production  of  glycerinated  calf  lymph  which  shall 
be  free  from  all  extraneous  organisms,  of  perfect  efficacy,  and  yet  afford- 
ing material  for  the  vaccination  of  many  more  children  than  the  original 
unglycerinated  calf  lymph,  is  briefly  as  follows: 

"The  Preparation  of  the  Calf. — A  female  calf  of  suitable  age, 
about  from  three  to  six  months,  should  be  kept  under  observation  for 
a  week,  after  which,  if  found  to  be  quite  healthy,  it  may  be  removed  to 
the  vaccination  station.  It  is  there  placed  on  a  tilting  table,  and  the 
lower  part  of  the  abdomen,  reaching  as  far  forward  as  the  umbilicus, 
is  shaved  and  thoroughly  washed  with  a  solution  of  carbolic  acid  and 
then  rinsed  with  sterile  water  and  dried  with  soft,  sterilized  towels. 

"  Inoculation  of  the  Calf. — With  a  sterilized,  sharp  scalpel  incisions 
about  four  inches  long  and  half  an  inch  apart,  parallel  to  the  long  axis 
of  the  body,  are  made  on  this  clean-shaven  area.  The  depth  of  the 
incision  should  be  such  as  to  pass  through  the  epidermis  and  to  open 
the  rete  Malpighii,  if  possible  without  drawing  blood.  As  these  incisions 
are  made,  glycerinated  calf  lymph,  which  by  examination  has  been 
proved  to  be  free  from  extraneous  organisms,  is  run  into  them  by  means 
of  a  sterilized  blunt  instrument,  and  the  point  of  the  scalpel  is  from 
time  to  time  dipped  into  the  vaccine  emulsion. 

"Collection  from  the  Calf. — After  five  days  (one  hundred  and 
twenty  hours)  the  vaccinated  surface  of  the  calf  is  first  thoroughly  washed 
with  warm  water  and  soap,  rubbed  over  it  by  the  clean  hand  of  the 
operator,  and  finally  the  whole  area  is  carefully  cleansed  with  sterile  water. 
The  remaining  moisture  is  then  removed  by  sterilized  sheets  of  blotting 
paper.  The  vaccinated  incisions  will  now  appear  as  lines  of  continuous 
vesicles  raised  above  the  surface,  each  line  separated  from  its  neigh- 
bor by  about  a  quarter  of  an  inch  of  clear  skin.    Aiiy  crusts  wliich  appear 

1  A  Study  of  Actinomyces  Cultivated  from  Commercial  Vaccine  Virus,  Journal  of  Medical  Researchj 
January,  1904. 


104    BELATIONSHIP  OF  COWPOX  OR  VACCINIA  TO  SMALLPOX 

in  the  vesicular  lines  are  picked  off  with  a  blunt,  sterilized  instrument. 
The  vesicles  and  their  contents  are  then  removed  by  means  of  a  steril- 
ized Volkmann  spoon,  and  transferred  to  a  sterilized  bottle  of  known 
weight.  By  going  over  the  lines  only  once  with  the  spoon,  it  is  quite 
easy  to  remove  the  whole  of  the  pulp  without  any  admixture  of  blood. 
The  abraded  surface  is  carefully  washed,  and  may  be  dusted  over  with 
fine  oatmeal  or  starch  and  boracic  powder.  Subsequently,  the  calf  is 
transferred  to  the  slaughter  house  and  the  carcass  is  examined  by  the 
veterinary  surgeon,  who  forwards  a  certificate  of  its  condition.  Should 
this  not  be  satisfactory,  the  vaccine  pulp  obtained  from  the  animal  is 
destroyed. 

Fig.  16 


Belly  of  heifer,  showing  one  of  the  approved  modern  methods  of  propagating  vaccine  virus ;  lesions 
photographed  at  the  end  of  five  days.    (Courtesy  of  Dr.  Wm.  F.  Elgin.) 

"Preparation  and  Glycerination  of  the  Lymph  Pulp. — ^The 
bottle  containing  the  vaccine  pulp  is  taken  to  the  laboratory  and  the  exact 
weight  of  the  material  ascertained.  A  calf  vaccinated  in  this  way  will 
yield  from  18  to  24  grams,  or  even  more,  of  lymph  pulp.  This 
material  is  then  thoroughly  rubbed  up  in  a  sterilized  mortar  or  in  a 
mechanical  triturating  machine.  When  it  has  been  brought  to  a  fine 
state  of  division,  it  is  mixed  with  six  times  its  weight  of  a  sterilized 
solution  of  50  per  cent,  chemically  pure  glycerin  in  distilled  water. 
The  resulting  emulsion  is  then  transferred  to  small  test-tubes,  which 
are  then  aseptically  sealed  and  should  be  stored  in  a  cool  place  protected 
from  light.  When  required  for  distribution  it  is  drawn  up  into  sterilized 
capillary  tubes,  which  are  subsequently  sealed  in  the  flame  of  a  spirit 
lamp. 


STATISTTCJAL  EVIDENCE  OF  EFFfdAdY  OF  VA  CO  f  NATION     lOo 

'Bacteriological  Examination  of  the  Lymph  Emulsion. — As 
soon  as  the  vesicular  pulp  is  thoroughly  emulsified  with  the  glycerin  solu- 
tion, agar-agar  plates  are  established  from  it,  and,  after  suitable  incubation 
for  seven  days,  the  colonies  that  have  developed  on  the  plates  are  counted 
and  examined.  Week  by  week  this  process  is  repeated,  and  invariably 
the  number  of  colonies  diminishes  with  the  age  of  the  emulsion,  until 
at  the  end  of  the  fourth  week  after  the  collection  and  glycerination  of 
the  lymph  material  the  agar-agar  plates  inoculated  at  that  time  show 
no  development  of  colonies.  The  lymph  is  then  subjected  to  further 
culture  experiments,  and  if  these  results  of  freedom  from  extraneous 
organisms  are  confirmed  the  emulsion  is  ready  for  distribution.  The 
elimination  of  the  extraneous  organisms  in  our  experiments  has  occurred 
with  marked  regularity  at  the  end  of  the  fourth  week.  The  only  excep- 
tion to  this  rule  arises  when  the  lymph  originally  contained  a  consider- 
able number  of  spores  or  bacilli  of  the  hay  bacillus  or  bacillus  mesen- 
tericus.  These  organisms  are  very  resistant  to  the  action  of  glycerin, 
but  if  the  precautions  detailed  are  carried  out  in  the  treatment  of  the 
calf  their  presence  may  generally  be  excluded. 

"Duration  of  Activity  of  Glycerinated  Calf  Lymph. — This 
varies  in  all  probability  with  atmospheric  conditions,  with  the  fineness  of 
division  of  the  vesicle  pulp,  and,  above  all,  with  the  condition  of  the  calf 
itself.  Some  calves  yield  an  excellent  lymph,  others  a  poor  lymph, 
and  the  problem  is  to  determine  the  value  of  the  lymph  yielded  by  any 
given  calf.  A  lymph  which  was  collected  and  glycerinated  on  July  13, 
1897,  has  since  been  used  at  intervals  of  from  twenty-four  weeks  to 
thirty-two  weeks  after  glycerination  for  the  vaccination  of  children. 
During  this  period  sixty-one  children  have  been  vaccinated  with  this 
lymph  in  five  places  each,  with  a  mean  insertion  success  of  98  per  cent. 
Thus,  by  the  methods  described,  glycerinated  calf  lymph  can  be  pre- 
pared which  becomes  freed  from  extraneous  organisms,  is  available 
for  a  large  number  of  vaccinations,  at  least  5000  from  an  average  calf, 
and  retains  full  activity  for  eight  months,  and  will,  under  favorable 
circumstances  continue  to  do  so  in  all  probability  for  still  longer  periods, 
if  necessary." 

STATISTICAL  EVIDENCE  OF   THE  EFFICACY  OF  VACCINATION. 

Although  smallpox  dates  back  many  centuries,  we  have  no  trust- 
worthy record  of  the  extent  of  its  prevalence  before  the  fifteenth  century. 
About  this  time  it  began  to  be  common  in  Western  Europe,  increasing 
during  the  sixteenth  and  particularly  the  seventeenth  century,  and 
prevailing  still  more  extensively  in  the  eighteenth. 

The  begimiing  of  the  nineteenth  century  was  characterized  by  a  sudden 
and  striking  decrease  in  the  morbidity  and  mortality  of  smallpox. 

Inasmuch  as  the  announcement  of  the  protective  influence  of  vac- 
cination (1798)  and  the  diffusion  of  this  practice  immediately  preceded 
this  decline,  there  is  the  strongest  reason  to  regard  Jenner's  epoch- 
making  discovery  as  the  causative  influence. 


106    RELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 


As  has  been  previously  shown,  smallpox  was  a  great  scourge  before 
the  days  of  vaccination.  But  a  small  percentage  of  the  population 
escaped  its  ravages.  It  is  claimed  that  in  the  eighteenth  century,  accord- 
ing to  contemporaneous  writers,  95  per  cent,  of  the  inhabitants  of 
European  countries  suffered  at  one  time  or  other  from  the  smallpox. 
In  other  words,  but  five  persons  out  of  every  hundred  went  through  life 
without  being  attacked  by  this  dread  malady.  This  is  rendered  credible 
when  we  appreciate  the  fact  that  smallpox  is  among  the  most  contagious 
of  all  diseases,  and  that  nearly  every  human  being  is  highly  susceptible 
to  it.  Haygarth,  who  lived  in  the  eighteenth  century,  stated  that  the 
proportion  of  mankind  incapable  of  infection  by  smallpox  "was  observed 
to  amount  to  one  in  twenty;"  this  would  account  for  the  exemption  of 
the  5  per  cent,  referred  to. 


Fig.  17 

annual  deaths  per  million  of  population. 


7000 


6000 


5000  - 


4000 


3000 


2000 


1000 

500 
0 


BEFORE  VACCINATION 

AFTER  VACCINATION 

SMALLPOX  WITH 
MEASLES 

SMALLPOX 

SMALLPOX 

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Smallpox  death  rates  for  Sweden  from  1749  to  1855.  (Calculated  by  Mr.  Haile  Ijom  returns  com- 
municated by  the  Swedish  government.  Published  in  papers  communicated  to  the  Houses  of 
Parliament,  London,  1857.) 

This  author  reports  an  epidemic  of  smallpox  in  Chester^in  1774,  at 
which  time,  out  of  a  population  of  14,713,  1202  persons  took  the  disease 
and  202  died.  At  the  termination  of  the  epidemic  there  were  but  1060 
persons,  or  7  per  cent.,  of  the  population  who  had  never  had  smallpox. 

In  an  epidemic  of  smallpox  at  Warrington  in  1773,  in  a  population 
of  8000,  211  persons  succumbed  to  the  disease.  The  total  deaths  during 
the  year  from  all  causes  were  473. 

In  1722  an  epidemic  raged  in  the  small  English  town  of  Ware,  which 
had  a  population  of  2515.  Of  this  number  there  were  only  914  persons 
susceptible  to  smallpox,  as  1601  had  already  had  the  disease.  During 
the  epidemic  612  persons  were  attacked,  leaving  but  302  individuals 
in  the  entire  town  who  had  never  had  smallpox. 


STATfSTKJylL  EVI I) l<:N<tl<:  <>l<'  l':FFI(!y\(JY  OF   VA(!(JINATI()N     107 

Rapid  Decline  in  Smallpox  Mortality  After  the  Introduction  of 
Vaccination. — iiiHsniuch  as  accurutc  rcf-ocds  of  siiKillpox  iMorlulity 
wiM'c  kept  ill  vjxrioiis  coiiiitrics,  it  is  possible  to  prove  by  (loeiiiiientary 
evidence  that  a  strikirif);  fall  in  the  niiiiihcr  of  deaths  from  this  disease 
oceurred  shortly  after  the  introduction  of  vaccination. 

Sweden. — Vaccination  was  introduced  into  this  country  in  Oetoher, 
1801.  According  to  the  official  fi<^ures  of  the  Medical  College,  there 
were  performed  2^), ()()()  vaccinations  hy  the  year  ISOo,  2."<,()()()  in  1S05, 
and  about  19,000  in  1800.  Vaccination  was  made  compulsory  in  1810. 
The  average  death  rates  per  million  of  j)opulation  for  the  decades  from 
1774  to  1821  show  a  decided  and  progressive  decrease  in  the  mortality 
of  smallpox.     (See  Fig.  17.) 

Average  Yearly  Death  Rates  from  Smai.ltox  per  Million  of 

PorULATION   FOR    DeCADES    FROM  1774   TO  1821.      SWEIiEN. 

(Bight  years),  1774  to  1781  (before  vaccination) 1999 

Decade,             1782  "  1791        "                 "  2219 

"                  1792  "  1801        "                "  1914 

"                 1802  "  1811  (after  vaccination) 623 

1812  "  1821        "                 "  133 

The  influence  of  vaccination  in  lessening  smallpox  mortality  in 
Sweden  is  so  clearly  shown  in  the  above  table  as  to  require  no  fuither 
discussion. 

The  contrast  in  smallpox  mortality  may  be  expressed  in  another 
manner.  In  the  twenty-eight  years  before  vaccination  in  Sweden,  there 
died  each  year  from  smallpox,  out  of  each  million  of  population,  2050 
persons;  during  the  forty  years  folloiving  vaccination,  out  of  each  million 
of  population  the  smallpox  deaths  annually  averaged  158. 

The  official  figures  of  the  Medical  Faculty  of  the  University  of  Prague 
(published  in  papers  on  vaccination  issued  by  the  London  Board  of 
Health,  1857)  are  no  less  conclusive: 

Population,  Total  Deaths,  and  Deaths  by  Smallpox  During  Seven 
Years  Before  the  General  Introduction  of  Vaccination.    Prague. 


Population. 

Deaths. 

Year. 

Total  number. 

From  smallpox. 

Remarks. 

1796 

1797 
1798 
1799 
1800 
1801 
1802 

3,003,482 

2,991,346 
3,045,926 
3,041,608 
3,047,740 
8,036,481 
3,111,472 

92,242 

86,855 
84,743 
99,079 
110,730 
105,576 
85,460 

6,6S6 

1,988 
3,105 
17,587 
17,077 
3,169 
4,029 

(The  proportion  of  the  deaths  generally 
\     to  population  =  1  :  32. 

/Deaths  from  smallpox  to  populations 
1       =  1  :  396P:,. 

/Deaths  from  smallpox  to  the  total 
t    number  of  deaths  =  1  :  12J^. 

Total 

21.278,055 

664,685 

53,641 

Average 

3.039,722Vt 

94,955 

7,663 

108    BELATIONSHIP  OF  GOWPOX  OR   VACCINIA   TO  SMALLPOX 


During  Twenty-four  Years  Subsequent  to  Introduction  op 
Vaccination.    Prague. 


Population. 

Deaths. 

Year. 

Remarks. 

Total  number. 

From  smallpox. 

1832  1 

1833  i 

3,888,828 

1 

139,061 
121,679 

807 
533 

1834  ■) 

i 

122,171 

285 

The  proportion  of  the  total  number 

1835    Y 

3,945,875 

122,952 

337 

of  deaths  to  popuJation  =  1 :  Z2%. 

1836  j 

( 

124,015 

291 

1837  ) 

(■ 

141,982 

104 

1838    Y 

4,027,581 

\ 

108,419 

62 

1839  J 

1 

121,400 

128 

1840  ") 

118,471 

699 

Deaths  from  smallpox  to  population 

1841    Y 

4,145,715 

) 

116,575 

697 

=  1 :  14,7413^. 

1842   ) 

j 

124,019 

339 

1843  ) 

( 

142,876 

332 

1844    Y 

4,285,730 

J 

118,184 

150 

1845   ) 

1 

178,826 

62 

1846  ■) 

j" 

132,379 

59 

Deaths  from  smallpox  to  total  number 

1847    Y 

4,480,661 

J 

134,490 

9 

of  deaths  =  1  :457^. 

1848  j 

j 

141,409 

115 

1849  ' 
1850 

131,493 

383 

176,211 

478 

1851    r 

4,613,080 

\ 

133,245 

508 

1852 

134,921 

343 

1853 

1 

124,617 

42 

1854  \ 

1855  1 

4,593,770 

{ 

124,746 
124,764 

68 
64 

Total 

33,985,240 

3,153,905 

6895 

Average 

4,248,155 

131,412' 7/24 

287 '/24 

Tables  Comparing  Smallpox  Mortality  in  Various  Localities  Before 
AND  After  the  Introduction  of  Vaccination. 


Terms  of  years  respecting 

which  particulars  are 

given. 


Before  After 

vaccination,    vaccination. 


1777-1806  and  1807-1850 

1777-1806 

"     1807-1850 

1777-1806 

'     1807-1850 

1777-1806 

'     1807-1850 

1777-1806 

'     1807-1850 

1777-1803 

'     1807-1850 

1777-1806 

'    1807-1850 

1777-1806 

'     1807-1850 

1777-1806 

'     1807-1850 

1777-1806 

'    1807-1850 

1787-1806 

'    1807-1850 

1817-1850 

1817-1850 

1817-1850 

1831-1850 

1776-1780 

'    1810-1850 

1780 

'     1810-1850 

1780 

'     1816-1850 

1776-1780 

'     1810-1850 

1776-1780 

'     1816-1850 

1776-1780 

'     1816-1850 

1781-1805 

'     1810-1850 

1776-1780 

'     1816-1850 

1780 

'    1810-1850 

1810-1850 

1774-1801     ' 

'    1810-1850 

1751-1800     ' 

'    1801-1850 

Territory. 


Austria,  Lower  . 

Austria,  Upper,  and  Salzburg 

Styria 

Illyria , 

Trieste 

Tyrol  and  Voralberg 

Bohemia 

Moravia 

Silesia  (Austrian) 

Gallicia 


Bukowina  . 

Dalmatia     . 

Lombardy  . 

Venice 

Military  Frontier 

Prussia  (East  Province) 

Prussia  (West  Province) 

Posen  . 

Brandenburgh    . 

Westphaha 

Rhenish  Provinces 

Berlin  . 

Saxony  (Prussian) 

Ponierania  . 

Silesia  (Prussian) 

Sweden 

Copenhagen 


Approximate  average. 
Annual  death  rate  by  smallpox 
per  million  of  living  population. 


Before  intro- 
duction of 
vaccination. 


2,484 
1,421 
1,052 

518 
14,046 

911 
2,174 
5,402 
5,812 
1,194 
3,527 


3,321 
2,272 
1,911 
2,181 
2,643 

908 
3,422 

719 
1,774 


After  intro- 
duction of 
vaccination. 


2,050 
3,128 


340 
501 
446 
244 
182 
170 
215 
255 
198 
676 
516 
86 
87 
70 
288 
556 
356 
743 
181 
114 
90 
176 
170 
130 
310 
158 
286 


STATIHTIdAf.  l<:Vn)ICN(!l<:  Oh'  KFFKIAdY  Oh'   VAdCfNATfOy     l()f) 

It  will  be  seen  from  the  above  tables  tliat  whereas  in  the  seven  years 
preceding  the  introduction  of  vaccination  smallpox  in  Prague  caused 
one-twelfth  of  the  total  numher  of  deaths,  this  disease  during  twenty 
years  of  the  vaccination  period  caused  but  -2^^-^  of  the  total  numher  of 
deaths. 

In  Westphalia  the  annual  deaths  from  smallpox  from  177G  to  1780 
were  2G43  per  million  of  population;  during  the  tliirty-five  years  from 
1816  to  1850  the  death  rate  was  only  114  per  million. 

In  Copenhagen,  for  the  half-century  1751  to  1800,  the  smallpox  death 
rate  was  3128,  whereas  for  the  next  fifty  years  it  was  only  286. 

In  Berlin  for  twenty-four  years  preceding  vaccination  the  death  rate 
from  smallpox  was  3422,  and  for  the  first  forty  years  of  the  vaccination 
era  it  was  176. 

By  the  middle  of  the  nineteenth  century  the  fatality  of  smallpox  had 
been  reduced  in  Copenhagen  to  one-eleventh  of  the  pre  vaccination 
death  rate;  in  Sweden  to  a  little  over  a  thirteenth;  in  Berlin,  and  in  a 
large  part  of  Austria,  a  twentieth;  and  in  Westphalia,  a  twenty-fifth. 
In  the  last-named  place  but  four  persons  died  about  the  middle  of  the 
century  compared  to  100  in  the  prevaccination  days. 

Smallpox  Deaths  Each  Year,  from  the  "  Bills  of  Mortality," 
London,  1801  to  1830. 

Before  vaccination  era.  After  vaccination  era. 


Decade. 

Smallpox  deaths. 

Decade. 

Smallpox  deaths 

1761-1770 

.    20,434 

1801- 

-1810 

12,534 

1771-1780 

.     20,923 

1811- 

-1820 

7,858 

1781-1790 

.     17,867 

1821- 

-1830 

6,990 

1791-1800 

.    18,477 

1801-1810 

1811-1820 

1821 

-1830 

1831- 

-1837 

1801  .     . 

1,461 

1811.     .     .    751 

1821. 

.     .     508 

1831. 

.    563 

1802.     . 

1,597 

1812  .     .     .  1287 

1822  . 

.     .     604 

1832. 

.    771 

1803  .     . 

1,202 

1813  ...    898 

1823. 

.     .    774 

1833. 

.     574 

1804.     .     . 

622 

1814  .     ,     .     638 

1824. 

.     .    725 

1834. 

.    334 

1805.     .     . 

1,685 

1815.     .     .    725 

1825. 

.     .  1299 

1835  . 

.    863 

1806  .     .     . 

1,158 

1816  ...    653 

1826. 

.     .    503 

1836. 

.    536 

1807  .     .     . 

1,279 

1817  .     .     .  1051 

1827. 

.     .    616 

1837. 

.    217 

1808  .     . 

1,169 

1818.     .     .     421 

1828. 

.     .     598 

1809  .     .     . 

1,163 

1819.     .     .     712 

1829. 

.     .    736 

1810.     .     . 

1,198 

1820  ...     722 

1830. 

.     .     627 

Smallpox, 

12,534 

78D6 

6990 

3858 

The  above  figures  show  a  decided  contrast  in  smallpox  mortality 
between  the  decades  immediately  preceding  and  following  the  intro- 
duction of  vaccination.  In  the  twenty-seven  years  elapsing  from  1811 
to  1837  the  smallpox  deaths  exceeded  1000  but  three  times. 

Berlin. — Below  are  compared  the  deaths  from  smallpox  per  100,000 
inhabitants  \\\  the  prevaccination  and  postvaccination  periods: 


1758-1762 

.        .    407 

persons. 

1790-1794 

.    310  persons 

1763-1767 

.    364 

" 

1795-1799 

.    239 

1768-1772 

.    294 

" 

1S00-1S04 

.    261 

1773-1784 

.      ? 

" 

1805-1809 

.    308 

1785-1789 

.    360 

" 

110     RELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 

(In  the  first  decade  of  the  nineteenth  century  vaccination  was  not 
actively  practised  in  BerHn;  it  became  generally  employed  in  the  year 
1810.) 


1810-1814     ^  . 

31  persons. 

1840-1844 

13  person 

1815-1819 

.      40 

1845-1849 

2 

1820-1824 

4 

1850-1854 

5 

1825-1829 

.      13 

1855-1859 

.      18 

1830-1834 

.      19 

1860-1864 

.      30 

1835-1839 

.       18 

1865-1869 

.      26 

In  the  quinquennium  1870-1874  occurred  the  great  pandemic  of 
smallpox  which  swept  the  entire  civilized  world.  There  died  in  Berlin 
during  this  period,  per  100,000  population,  a  yearly  average  of  160; 
this  number  considerably  exceeds  all  the  previous  years  of  this  period, 
but  still  falls  far  below  the  average  of  the  prevaccination  years. 

From  1795  to  1799,  before  the  days  of  vaccination,  smallpox  caused 
6.5  per  cent,  of  all  deaths  in  Berlin.  In  the  five  years  following  the 
introduction  of  vaccination  the  figures  were:  7.5  per  cent.,  6.4  per  cent., 
0.7  per  cent.,  1.3  per  cent.,  and  0.2  per  cent.^ 

Copenhagen. — Between  1794-1798  (prevaccination  period)  smallpox 
caused  on  an  average  373  deaths  each  year. 


1799  (before  vaccination)  . 

.     54 

1800 

.     35 

1801 

.  486 

1802 

.    73 

1803  (after  vaccination)    . 

.      5 

1804 

.     13 

805  (after  vaccination) 
806 


809 
810 


From  1811  to  1823  not  a  death  occurred  from  smallpox.  (A  period  of 
thirteen  years. )^ 

It  is  thus  seen  from  the  statistics  above  quoted  that  after  the  discovery 
of  vaccination  the  deaths  from  smallpox  markedly  decreased  in  every 
country  in  which  this  practice  was  introduced. 

1  Denkschrift,  li.  k.  Gesundheitsamt,  Berlin. 

-  Beitrage  aus  der  Gesundheitsamte.    Quoted  by  Edvvardes,  Smallpox  and  Vaccination  in  Europe, 
London,  1902. 


STATISTICAL   KV I  I)I<:N<II<:  01''  I'^FFKIAd  )    OF    VAdfJI  NATION     \\] 


ACTUAl.   SMAMil'OX 

DiCATHH    IN 

SWKDKN    IJkFOKIO    AND    AlTIOl 

.   THK 

Intkoduotion 

OK  Vaccination. 

n-l!)  (before  viK^oimiUoii)    .       .     4,4r)3 

1802       (after  vaccination; 

1,533 

1750        "               "        .        . 

6,180 

1803           "                 "            .        . 

1,404 

1751 

5,546 

1804           •'                •'           .        . 

1,400 

1752 

10,302 

1805           "                "           .        . 

1 ,090 

1753        "                "        . 

8,000 

1806            "                 "            .        . 

1,482 

1754        "               " 

6,862 

1807            "                  "            .        . 

2,129 

1755 

4,705 

1808 

1,814 

1756 

7,858 

1809 

2,404 

1757 

10,241 

1810 

824 

1758 

7,104 

1811 

689 

1759 

3.910 

1812 

404 

1760 

3,568 

1813 

547 

1701 

5,731 

1814 

308 

1762        "               "        . 

9,389 

1815 

472 

1763 

11,662 

1816 

690 

1764 

4,562 

1817  (compulsory  vaccination) 

242 

1765 

4,697 

1818 

305 

1766 

4,092 

1819 

161 

1767 

4,189 

1820 

143 

1768 

10,650 

1821 

37 

1769 

10,215 

1770 

5,215 

Total  (20  years)    . 

.   18.217 

1771        " 

4,362 

1772 

5,435 

1822  (compulsory  vaccination) 

11 

1773 

12,130 

1823 

39 

1774 

2,065 

1824 

618 

1775 

.      1,275 

1825 

1,243 

1776 

1,503 

1826 

626 

1777 

.      1,943 

1827 

600 

1778 

.      6,607 

1828 

257 

1779        " 

15,102 

1829 

53 

1780 

.      3,374 

1830 

104 

1781 

.      1,485 

1831 

612 

1782 

.      2,482 

1832 

622 

1783 

.      3,915 

1833 

.     1,145 

1784 

.    12,456 

1834 

1,049 

1785 

.      5,077 

1835 

445 

1786 

671 

1836 

138 

1787        " 

1,771 

1837 

361 

1788 

.      5,462 

1838 

.     1,805 

1789 

.      6,764 

1839 

.     1,934 

1790 

.      5,893 

1840 

650 

1791 

.      3,101 

1841 

237 

1792 

.      1,939 

1842 

58 

1793 

.      2,103 

1843            " 

9 

1794 

.      3,964 

1844 

6 

1795 

.      6,740 

1845 

6 

1796        " 

.      4,503 

1846 

2 

1797 

1,733 

1847 

13 

1798 

1,357 

1848 

71 

1799 

3,756 

1849 

341 

1800 

12,032 

1850 

1,376 

1801 

6,057 

1851            "       ,         " 

2,488 

1852            ..        '         « 

1,534 

Total  (53  years)  .        .        .  125,130 

1853 

279 

1854 

204 

1855 

41 

The  population  iu  1751  was 

1.785.727 

" 

" 

15 

)55     " 

3,639,332 

112    RELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 


Smallpox  Mortality  pee 

MiLLIOlS 

Living,  Sweden,  1774  to  1893. 

Before 

Permissive 

vaccination. 

vaccination. 

Era  of  compulsory  vaccination,  1817-1893. 

1774  .  .  .  1020 

1802  ...   644 

1817  ...   96 

1845   ...   2 

1878  .  . 

265 

1775 

631 

1803  . 

611 

1818  . 

120 

1846 

1 

1874  .  . 

936 

1776 

737 

1804  . 

605 

1819  . 

63 

1847 

4 

1875  .  . 

484 

1777 

943 

1805  . 

449 

1820  . 

55 

1848 

21 

1876  .  . 

136 

1778 

3178 

1806  . 

613 

1821  . 

14 

1849 

99 

1877  .  . 

79 

1779 

7196 

1807  . 

884 

1822  . 

4 

1850 

395 

1878  .  . 

44 

1780 

1593 

1808  . 

.  757 

1823  . 

15 

1851 

707 

1879  .  . 

31 

1781 

699 

1809  . 

1007 

1824  . 

226 

1852 

433 

1880  .  . 

38 

1782 

1165 

1810  . 

347 

1825  . 

449 

1853 

78 

1881  .  . 

65 

1783 

1832 

1811  . 

291 

1826  . 

223 

1854 

57 

1882  .  . 

34 

1784 

6810 

1812  . 

167 

1827  . 

212 

1855 

11 

1883  .  . 

27 

1785 

2361 

1813  . 

225 

1828  . 

90 

1856 

14 

1884  .  . 

12 

1786 

311 

1814  . 

126 

1829  . 

19 

1857 

132 

1885  .  . 

0.8 

1787 

823 

1815  . 

191 

1830  . 

36 

1858 

345 

1886  .  . 

0.2 

1788 

2534 

1816  . 

277 

1831  . 

211 

1859 

388 

1887  .  . 

0.6 

1789 

3137 

1832  . 

213 

1860 

184 

1888  .  '. 

1.5 

1790 

2734 

1833  . 

387 

1861 

49 

1889  .  . 

0.4 

1791 

1421 

1834  . 

352 

1862 

37 

1890  .  . 

0.2 

1792 

878 

1835  . 

147 

1863 

76 

1891  .  . 

0.2 

1793 

942 

1836  . 

45 

1864 

182 

1892  .  . 

0.8 

1794 

1757 

1837  . 

117 

1865 

323 

1893  .  . 

5.0 

1795 

2955 

1838  . 

583 

1866 

292 

1796 

1963 

1839  . 

621 

1867 

252 

1797 

751 

1840  . 

207 

1868 

342 

1798 

585 

1841  . 

75 

1869 

354 

1799 

1609 

1842  . 

18 

1870 

183 

1800 

5126 

1843  . 

3 

1871 

< 

78 

1801 

2563 

1844  . 

2 

1872 

81 

Average,  2045 

Average,  480 

Average  of  77  years,  155 

Change  in  the  Age  Incidence  of  Smallpox. — In  the  prevaccination 
days  smallpox  was  essentially  a  disease  of  children  and,  indeed,  was  desig- 
nated Kindspocken  (childpox),  or  Kindsblattern.  Owing  to  the  extreme 
contagiousness  and  the  almost  universal  susceptibility  to  smallpox  the 
vast  majority  of  people  contracted  the  disease  in  childhood,  and  the 
adult  population  being  made  up  largely  of  survivors  was  thus  immunized. 

The  conditions  in  relation  to  smallpox  were  much  as  they  are  at  the 
present  day  in  regard  to  measles.  Comparatively  few  adults  contract 
measles  because  the  great  bulk  of  the  people  pass  through  the  disease 
in  infancy. 

As  an  instance  of  the  incidence  of  smallpox  among  children  in  the 
prevaccination  days,  an  epidemic  occurring  in  1795-96,  described  by 
Schwarz,^  is  here  referred  to.  The  epidemic  occurred  in  Rawicz,  Boja- 
nowo,  and  Sarnowo  in  the  Prussian  province  of  Posen.  The  entire 
population  of  the  three  towns  at  the  beginning  of  the  epidemic  was 
13,329.  Of  this  number  1252,  or  9.4  per  cent.,  were  attacked  with 
variola,  and  199,  or  1.5  per  cent,  of  the  population  and  15.9  per  cent, 
of  the  infected,  died.  At  the  end  of  the  epidemic  there  were  only  524 
people  remaining  who  were  susceptible  to  the  disease.  The  1252 
patients  were  of  the  following  ages: 


Under  5  years  . 
Between  5  and  10  years 
Over  10  years    . 


743  persons,  or  59.3  per  cent. 
441  "  35.2       " 

68  "  5.2        " 


Quoted  by  Immerman,  Nothnagel's  Encyclopedia  of  Practical  Medicine,  p.  225. 


NTATfSTKJAIj  l<JVl  Dl'JNdl'J  <)!<'  I'JFFK'yid  V  OF    V  Add  I  \' M'l  0  \      \\, 


It  is  tliiis  seen  tJiiit  !)4.S  per  cciil.  of  (lie  palictifs  were  iiikI'I'  ten  vcars 
of  a^c. 

The  almost  exclusive  mortality  of  smii.ll|)o.\  ;iiiion<^  iiif;iiits  jiikI 
children  is  also  exemplified  in  the  suiidlpox  statistic-s  of  Kilm;irtiocl< 
from  172(S  to  1764,  a  p(>riod  of  thirty-one  years.  During  this  time  the 
total  deaths  were  .'iSfJO,  and  the  deaths  from  smallj)ox  022.  'I'here  were 
nine  epidemics  of  smallpox  reenrrin<i;  jit  intervals  of  ahont  four  years. 
Of  tlw  ()22  fimallpox  drat/i.s,  5S()  'uu'rr  In  cliildrrn  under  .v/.r  //rnr.s  of  age; 
27  occurred  in  persons  over  the  a(jje  of  six,  and  the  a>i;e  of  nine  person.s 
was  not  known. 

In  ChcMcr, in  the  epidemic  of  1774,  all  of  the  smallpox  deaths,  nuiidxT- 
inn^  202,  occurred  in  children  under  ten  years  of  age,  and  onc-(|ii;irter 
of  them  under  one  year. 

In  Kilmarnock,  of  622  deaths  from  smallpox  l)etween  172S  and  1763, 
only  seven  were  of  those  above  ten  years. 

In  1773,  Warrington^  sustained  an  epidemic  of  smallpox  which 
resulted  in  211  deaths  (population  SOOO).  In  1S03  another  epiflemic 
occurred  which  resulted  in  62  deaths  (population  54,084,  of  whom  53,645 
were  vaccinated).  The  ages  of  the  patients  fatally  attacked  are  tabulated 
as  follows: 


Smallpox  Deaths. 


Age. 


Under 

1 

year 

1    to 

2 

years 

2    " 

3 

3    " 

4 

4     " 

5 

5     " 

6 

6     " 

7 

7     " 

8 

8     " 

9 

9     " 

15 

15     " 

20 

20     " 

30 

30     " 

60 

Over 

60 

773. 

Vaccinated. 

Not  vaccinated. 

49 

0 

8  (under  1  month) 

84 

0 

1 

33 

0 

0 

18 

0 

1 

15 

0 

1 

4 

0 

0 

2 

0 

0 

2 

0 

0 

4 

1 

1 

0 

1 

1 

0 

1 

2 

0 

10 

4 

0 

24 

5 

0 

1 

0 

211 


24 


In  1773  all  of  the  deaths  were  under  ten  years,  and  nine-tenths  were 
under  five  years  of  age. 

In  1893  among  the  vaccinated  not  a  death  occurred  under  eight  years 
of  age;  indeed,  not  one  vaccinated  child  under  eight  years  of  age 
contracted  smallpox. 

The  statement  may  be  considered  as  proven  that  vaccination  has 
changed  the  age  incidence  of  smallpox.  It  is  a  rarity  for  a  successfully 
vaccinated  child  under  five  years  of  age  to  die  of  smallpox.  It  is  even 
uncommon  for  a  successfully  vaccinated  child  under  ten  years  to 
succumb  to  the  disease,  as  will  be  seen  from  the  following  table  compiled 
by  the  British  Royal  Vaccination  Commission: 


Quoted  by  Edwardes,  loc.  cit. 

S 


114    RELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 
Smallpox  in  Children  of  the  Age  of  1  to  10  Years. 

Vaccinated.  Not  vaccinated. 

Attacks 570  Attacks 1235 

Deathsi 16  Deaths 375 

Fatality        .       .       .       .2.8  per  ct.  Fatality       ....  30.3  per  ct. 

The  saving  of  infant  life  by  vaccination  should  have  reduced  the 
general  infant  mortality  in  the  postvaccination  period;  the  following 
table  shows  that  such  a  reduction  in  infant  mortality  did  take  place. 
It  will  be  seen  that  the  diminution  in  the  general  death  rate  of  children 
under  ten,  and  more  particularly  under  five  years  of  age,  is  far  more 
pronounced  than  during  adult  life. 

Annual  Mortality  to  1000  Persons  Living.    Sweden, 


Before  vaccination. 

After  vaccination. 

Ages. 

21  years 

20  years 

20  years 

10  years 

(1755-1775). 

(1776-1795). 

(1821-1840). 

(1841-1850). 

Under    5  years  ...... 

90.1 

85.0 

64.3 

56.9 

5   to    10      " 

14.2 

13.6 

7.6 

7.8 

10    "    15      " 

6.6 

6.2 

4.7 

4.4 

15    "    20      " 

7.6 

7.0 

4.9 

4.8 

20    "    30      " 

9.2 

8.9 

7.8 

6.8 

30    "    40      " 

12.2 

11.6 

11.8 

9.8 

40    "     50      " 

17.4 

16.1 

16.7 

14.5 

iSO    "     60      " 

26.4 

23.9 

26.0 

23.6 

60    "     70      " 

48.1 

49.3 

49.4 

46.3 

70    "     80      " 

102.3 

104.1 

112.9 

102.8 

80     "    90      " 

207.8 

197.4 

243.7 

228.5 

90      "      and  upward 

394.1 

351.3 

396.4 

375.8 

All  age 

s 

28.9 

26.8 

23.3 

20.5 

The  opponents  of  vaccination  urge  that  the  decline  of  mortality  from 
smallpox  at  the  beginning  of  the  nineteenth  century  was  not  due  to 
vaccination,  but  to  the  discontinuance  of  inoculation. 

It  is  probable  that  inoculation  did  tend  to  increase  the  prevalence  of 
smallpox,  but  there  is  no  evidence  to  prove  that  it  increased  the  mortality. 
As  the  Royal  Commission  remarks:  "It  must  be  borne  in  mind  that 
inoculated  smallpox  was  on  the  whole  much  less  fatal  than  that  naturally 
acquired.  The  class  of  inoculated  persons  may  thus  have  contributed 
less  to  the  fatal  cases  of  smallpox  than  if  they  had  been  left  to  the  chances 
of  natural  contagion." 

While  inoculation  was  introduced  into  England  in  1721,  it  found  but 
Httle  favor  until  1740.  The  Suttons  popularized  the  practice  in  1763, 
and  between  1770  and  1780  it  was  widely  employed.  Inoculation  was 
therefore  only  practised  on  a  large  scale  in  England  in  the  second  half 
of  the  eighteenth  century,  and  particularly  in  the  last  twenty-five  years 
of  this  period.  The  antivaccinationists  claim  that  the  increase  of  small- 
pox mortality  in  the  eighteenth  century  over  the  seventeenth  was  due 
to  the  practice  of  inoculation.  If  this  were  true,  the  mortality  should 
have  shown  its  increase  particularly  during  the  second  half  of  the 


I  Six  of  tiiese  deaths  occurred  in  children  in  whom  the  success  of  the  vaccination  was  doubtful. 


STATISTIC  A  Ij  KV  f  DICNd  K  Oh'  KI^'lCAdY  Oh'   VAddlNATIOS     1|5 

century.  But  the  mortality  wus  as  n;rca(,  fil"  woi  ^n-c;i(<r;  diiiin^r  iIk; 
first  quarter,  wlien  tliere  was  j^raetically  no  iiiocnliifioii,  as  diinti^  the 
last  ({iiartc^r  of  tlie  ceiitiiry,  wlieri  inoculation  was  greatly  in  vogue. 

In  Sweden,  where  inoculation  was  never  practised  to  any  extent,  the 
fall  insmall])()X,  after  the;  introduction  of  vaccination,  was  as  f)rononnccd 
as  in  any  country. 

Again,  it  must  he  rcincnd)cn>d  (,li;it  inocnhition  did  not  cntir-cly  cease 
in  England  upon  the  introduction  of  vaccination,  but  continued  to  be 
practised  for  a  number  of  years,  until  it  was  declared  illegal  by  act  of 
Parliament  in  1(S40. 

It  is  evident  from  these  considerations  that  the  disc<jntinuanee  of 
inoculation  was  to  no  a])])recial)le  extent  the  cause  of  the  diminution  of 
smallpox  mortality  at  the  beginning  of  the  nineteenth  century. 

It  has  also  been  claimed  by  the  opponents  of  vaccination  that  the 
decline  in  the  prevalence  of  smallpox,  dating  from  the  beginning  of  the 
nineteenth  century,  was  due  to  improvement  in  sanitary  conditions. 

It  may  be  conceded  that  such  improvements  as  better  drainage  and 
sewerage,  freer  ventilation,  purer  water  supply,  lessened  crowding  in 
dwellings,  and  the  like  would,  by  improving  the  average  individual  health, 
tend  to  lessen  the  fatality  of  all  infectious  diseases,  not  excluding  smallpox. 
But  such  influences  are  totally  inadequate  to  explain  the  striking  and 
progressive  decline  in  the  prevalence  and  mortality  from  smallpox  that 
followed  the  introduction  of  vaccination. 

If  sanitary  improvements  were  responsible  for  the  lessened  mortality 
from  smallpox,  why  did  they  not  similarly  influence  the  mortality  from 
measles,  scarlet  fever,  and  whooping-cough,  which  are  favored  by  the 
same  conditions  that  aid  the  dissemination  of  smallpox?  Smallpox  and 
measles  resemble  each  other  in  the  sense  that  the  spread  of  both  diseases 
is  not  dependent  upon  any  special  sanitary  defect.  Unlike  typhoid  fever 
and  cholera,  their  occurrence  is  influenced  by  personal  infection  rather 
than  by  any  definite  vices  of  sanitation.  Measles  and  smallpox  are  the 
most  contagious  of  all  diseases;  a  momentary  exposure  of  an  unprotected 
person  to  the  infection  of  smallpox  or  measles  suffices  for  such  individual 
to  contract  the  disease.  According  to  the  Registrar  General's  Reports, 
during  the  same  period  in  England  that  smallpox  mortality  has  declined 
72  per  cent.,  the  mortality  from  measles  has  fallen  only  9  per  cent. 
Furthermore,  the  death  rate  from  whooping-cough  has  declined  but  a 
little  more  than  1  per  cent.,  and  the  diminution  in  the  mortality  of 
scarlet  fever  has  only  become  apparent  within  comparatively  recent 
years.  Again,  the  improvement  in  sanitation  and  mode  of  living  has 
only  caused  a  reduction  of  the  general  death  rate  of  the  country  of 
9  per  cent. 

Another  noteworthy  fact  must  not  be  forgotten — namely,  that  the 
decline  in  the  death  rate  from  smallpox  has  been  entirely  limited  to 
persons  below  the  age  of  fifteen.  It  is  evident,  therefore,  that  the  lives 
of  an  enormous  number  of  children  have  been  saved.  Above  fifteen 
years  of  age  the  smallpox  mortality  for  obvious  reasons  has  not  decreased. 
It  is  the  height  of  absurdity  to  attempt  to  explain  such  an  inequality 


116     RELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 

in  the  decline  of  smallpox  mortality  on  the  grounds  of  improved  sanita- 
tion. The  percentage  of  mortality  borne  by  children  the  subjects  of 
measles,  scarlet  fever,  and  whooping-cough  does  not  differ  materially 
from  what  it  was  a  century  ago. 

Vaccination  and  Sanitation  in  Glasgow. — -In  1780  the  population  of 
Glasgow  was  43,832;  by  1831  it  had  increased  to  202,000.  The  area 
occupied  was  very  small,  and  large  and  closely  built  tenement  houses 
were  erected  to  accommodate  the  growing  population.  Reports  made 
in  1818,  1837,  and  1838  indicated  that  the  sanitary  conditions  were 
extremely  bad,  perhaps  worse  than  those  of  any  large  town  in  Great 
Britain.  Whooping-cough  was  on  the  increase  and  measles  had  become 
much  more  extensively  prevalent.  There  was  no  disinfection  and  no 
isolation  in  hospitals.  Despite  all  of  these  unfavorable  conditions 
smallpox  became  decidedly  less  prevalent  and  less  fatal.  Before  vacci- 
nation was  practised,  smallpox  caused  19  out  of  every  100  deaths; 
within  six  years  after  the  introduction  of  vaccination  this  number  was 
reduced  to  9  and  after  another  period  of  six  years  to  less  than  4.  Thus 
it  is  seen  that  with  an  increasing  population,  with  sanitation  growing 
worse,  with  measles  deaths  multiplying,  the  mortality  from  smallpox 
decreased  almost  80  per  cent} 

Smallpox  in  the  Vaccinated  and  Unvaccinated. — If  vaccination  had 
no  protective  influence  against  smallpox  it  would  be  logical  to  conclude 
that  there  should  be  no  material  difference  between  the  mortality  of 
this  disease  in  vaccinated  and  unvaccinated  persons.  But  the  experience 
of  over  one  hundred  years  offers  absolutely  conclusive  proof  that  there  is 
a  most  pronounced  difference  in  smallpox  mortality  in  these  two  classes. 
There  has  never  been  an  epidemic  of  smallpox  in  any  country  of  the 
world  in  which  the  death  rate  among  the  vaccinated  has  not  been 
decidedly  lower  than  that  among  the  unvaccinated. 

Epidemics  of  smallpox,  like  epidemics  of  all  infectious  diseases,  vary 
greatly  in  malignancy.  Diphtheria,  scarlet  fever,  measles,  and  in  fact 
all  of  the  transmissible  diseases  appear  at  times  in  virulent  form  accom- 
panied by  high  mortality,  and  at  other  times  in  mild  form  with  corre- 
spondingly lower  death  rates. 

These  variations  apply  equally  well  to  smallpox,  and  are  produced 
by  circumstances  the  nature  of  which  are  poorly  or  not  at  all  under- 
stood. When  severe  epidemics  of  smallpox  prevail  the  mortality  rate 
is  increased  both  among  the  vaccinated  and  unvaccinated.  Variations 
in  the  severity  of  the  disease,  however,  need  not  in  the  least  degree 
complicate  the  comparative  study  of  the  fatality  in  the  vaccinated  and 
unvaccinated. 

1  Jenner  Number  of  Public  Health,  May,  1896. 


STATTSTTGAL  /<JVI/>/'JN(,'J<J  OF  ICFFfCAdY  OF   VACC'fNA'J'fOX     WJ 


DEATir  Rate  oiy  SMAi^riPOx  Amoncj  Vacxjinateo  and  Unvaccinatei;  in 

Various  Countries. 


Death  rate  per  100  casefi. 

Total  number 

of  cases 

Places  and  times  of  observation. 

observed. 

Among  the 

AmnnK  the 

10,397 

un  vaccinated. 
1(5  J^ 

vaccinated. 

France,  1816-1841 

1 

Qnebec,  1819-1820  . 

? 

27 

i% 

Philadelphia,  1825 

140 

60 

0 

Oaiitou  Vaud,  1825-1829 

5,8.38 

24 

2% 

Darkehmeii,  1828-1829  . 

134 

l«*/f, 

0 

Verona,  1828-1829  . 

909 

40^, 

5% 

Milan,  1830-1851     . 

10,240 

^'A 

^% 

Breslau,  1831-1833 

220 

53^/6 

2'/b 

Wiirtemberg,  1881-1835 

1,442 

27K 

Vlu, 

Carniola,  1834-1835 

442 

m 

4% 

Vienna  Hospital,  1834  . 

360 

51  >X 

12'A 

Carinthia,  1834-1835      . 

1,626 

14^ 

Yt. 

Adriatic,  1835 

1,002 

15'/5 

H 

Lower  Austria,  1835 

2,287 

25</r, 

n}4 

Bohemia,  1835-1855 

15,640 

294/s 

5^ 

Gallicia,  183(i 

1,059 

233^ 

5V7 

Dalmatia,  1836 

723 

19^ 

8'i 

London  Smallpox  Hospital 

183( 

)-185 

; 

9,000 

35^' 

7 

Vienna  Hospital,  1837-56 

6,213 

30 

5 

Kiel,  1852-1853 

218 

32 

6 

Wiirtemberg,  no  date  . 

6,258 

38'-V,o 

S'A 

Malta,  no  date 

7,570 

21.07 

4.2 

Epidemiological  Society  Returns,  no  date 

4,624 

19.7 

2.9 

The  above  figures  show  that  among  thousands  of  cases  of  smallpox 
occurring  in  cities  all  over  the  world,  the  death  rate  from  smallpox  has 
been  from  fi.ve  to  sixteen  times  greater  among  the  unvaccinated  than  among 
the  vaccinated. 

Vaccinated  and  Non- vaccinated  Cases  of  Smallpox  which  Terminated 
Fatally,  according  to  Official  Vaccination  Eeturns  (21  Years), 
Prague. 


Smallpox. 

Remain- 
ing non- 

Cases  of 

Cases. 

Deaths. 

Year. 

vacci- 
nation. 

vacci- 
nated. 

Remarks. 

Vacci- 

Non-vac- 

Vacci- 

Non-vac- 

nated. 

cinated. 

nated. 

cinated. 

1835 

132,727 

4,029 

505 

430 

20 

136 

1836 

130,194 

3,319 

374 

215 

26 

64 

1837 

126,123 

3,971 

57 

123 

4 

52 

1838 

133,527 

3,967 

101 

96 

15 

.S2 

1839 

132,523 

3,906 

160 

168 

20 

70 

One  case  of  smallpox  oc- 

1840 

140,898 

3,585 

1138 

966 

89 

351 

curs  among 

1841 

139,471 

3,482 

1583 

1522 

83 

382 

1842 

142,970 

3,180 

681 

703 

39 

208 

12^3  non-vaccinated. 

1843 
1844 

142,314 
126,647 

2,874 
6,109 

627 
61 

714 

148 

21 

7 

229 
43 

One  fatal  case  of  smallpox 

1845 

149,612 

6,410 

55 

63 

2 

25 

occurs  among 

1846 

146,467 

5,475 

6 

50 

7 

1847 

141,268 

5,361 

19 

25 

4 

1848 

132,320 

5,718 

227 

169 

17 

49 

1849 

139,523 

5,704 

575 

645 

63 

177 

Among  cases  of  smallpox 

1850 

156,561 

6,314 

568 

374 

14 

131 

died  the 

1851 

152,294 

4,694 

16 

293 

3 

43 

19th  part  of  the  vacci- 

1852 

161,364 

3,689 

252 

231 

12 

65 

nated. 

1853 

145.038 

3,067 

327 

168 

3 

39 

3d  part  of  the  non- vac- 

1854 

161,313 

2,927 

457 

203 

7 

61 

cinated. 

1855 

136,424 

2,349 

389 

156 

8 

56 

Total, 

3,005,578 

90,130 

8178 

7462 

423 

2224 

Average, 

143,12216/21 

4,29118/21 

3S9»/2i 

S557/21 

203/.1 

lOSio/oi 

118    RELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 

In  a  period  covering  twenty-one  years  from  1835  to  1855  in  Prague 
official  returns  show  that  whereas  one-third  of  all  unvaccinated  cases  of 
smallpox  died,  but  one-nineteenth  of  the  vaccinated  cases  succumbed  to 
the  disease. 

The  following  figures  of  an  epidemic  of  smallpox  at  Marseilles  in 
1828  indicate  the  marvellous  fact  that  but  J  per  cent,  of  the  vaccinated 
died  of  smallpox,  whereas  among  the  unvaccinated  the  death  rate  was 
25  per  cent.  The  fatality  among  the  unvaccinated  was  therefore  fifty 
times  greater  than  among  the  vaccinated. 


Marseilles,  1828. 

Number. 

Cases  of 
smallpox. 

Deaths  by 
smallpox. 

Total  number  of  persons  at  the  ages  (0-30)  which  were  ) 
almost  exclusively  susceptible \ 

1.  Protected  by  previous  smallpox       .... 

2.  Protected  by  vaccination 

3.  Unvaccinated 

40,000 

2,000 
30,000 
8,000 

6,020 

20 
2,000 
4,000 

1,024 

4 

20 

1,000 

Chemnitz^  (Saxony). — According  to  Dr.  Flinzer  the  population  of 
Chemnitz  at  the  time  of  the  epidemic  of  1870-71  was  64,222;  of  this 
number  53,891,  or  84  per  cent.,  were  vaccinated,  and  5712,  or  9  per  cent., 
were  unvaccinated;  in  addition  4652,  or  7.3  per  cent.,  had  previously  had 
smallpox. 

Of  the  vaccinated  935  took  the  disease  and  7,  or  0.7  per  cent.,  died; 
of  the  unvaccinated  2643  took  the  disease  and  243,  or  9.2  per  cent., 
died.  The  mortality  among  the  unvaccinated  was  almost  twelve  times 
greater  than  among  the  vaccinated. 

The  relative  mortality  from  smallpox  for  the  unvaccinated  population 
was  326  times  greater  than  for  the  vaccinated. 

Waldheim^  (Saxony). — The  epidemic  in  this  town  from  1872-73 
presents,  according  to  Miiller's  figures,  a  similar  condition  of  affairs. 
The  population  at  the  beginning  of  the  epidemic  was  5055,  of  whom 
4713,  or  93.2  per  cent.,  were  vaccinated,  and  342,  or  6.2  per  cent., 
unvaccinated.  Altogether  250  persons  were  attacked,  of  whom  66  died. 
Of  124  vaccinated  persons  11  died,  giving  a  mortality  rate  of  8.9  per 
cent.  Of  126  unvaccinated  who  took  the  disease,  55  died,  yielding  a 
death  rate  of  43.7  per  cent.  The  relative  mortality  from  smallpox  for 
the  unvaccinated  populatio7i  was  sixty-nine  times  greater  than  for  the 
vaccinated. 

The  British  Royal  Commission  on  Vaccination  presents  the  statistics 
of  six  recent  epidemics  in  Dewsbury  1891-92,  Warrington  1892-93, 
Leicester  1892-93,  London  1892-93,  Gloucester  1892-93  and  Sheffield. 
A  grand  total  of  11,065  attacks  is  collected;  this  number  resulted  in 
1283  deaths,  or  11.5  per  cent.,  divided  as  follows: 

Vaccinated.  Unvaccinated. 

Cases 8744  2321 

Deaths 461  822 

Per  cent 5.2  35.4 

1  Quoted  by  Immerman,  loc.  cit.  ^  Ibid. 


STATISTIdAI^  KVIDENdK  OF  KFFICAdY  OF   VACdlNATrON    HO 

The  death  rate  is  therefore  seven  timeH  (jr eater  anion (j  the  unvaccinated 
than  among  the  vaccinated. 

If  children  under  ten  years  of  af^e  are  alone  considc-rcd,  the  result,  is 
still  more  remarkable. 

eiiil'lrcii  uii'ler  the  age  of  10  years. 
Vaccinated.  Unvaccinatert. 

Cases oSO  1449 

Deaths        . 16  523 

Per  cent 2.7  36 

If  vaccination  confers  no  protection  against  smallpox,  how  can  this 
signal  difference  in  the  death  rates  of  the  two  classes  be  explained? 
Some  influence  must  have  been  at  work  which  caused  the  one  class 
to  suffer  less  fatality  than  the  other. 

Eliminating  all  children  under  one  year  of  age  (who  might  by  reason 
of  tender  age  fall  easier  prey  to  the  disease)  the  Commission  still  found 
the  most  striking  difference  in  the  fatality.  Ainong  the  vaccinated  the 
death  rate  was  2.8  per  cent,  as  compared  with  30.3  per  cent,  in  the 
unvaccinated. 

It  is  impossible  to  evade  the  conclusion  that  vaccination,  being  the 
only  circumstance  to  differentiate  the  two  classes,  must  have  been  the 
influence  operating. 

The  opponents  of  vaccination  are  fond  of  cpioting  the  statistics  of  the 
epidemic  at  Leicester  in  1892-93.  The  facts  are  as  follows:  Two 
vaccinated  children  were  attacked  with  smallpox,  neither  of  whom 
died.  Of  unvaccinated  children  of  the  same  age  period,  107  were 
attacked,  of  whom  15,  or  14  per  cent.,  died.  Over  ten  years  of  age,  197 
vaccinated  persons  were  attacked,  of  whom  2  died,  or  1  per  cent.  Of 
unvaccinated  persons  over  ten  years  of  age,  51  were  attacked,  of  whom 
4,  or  7.8  per  cent.,  succumbed.  Surely  there  is  nothing  in  these  figures 
to  disprove  the  efficacy  of  vaccination  as  a  life-saving  agent. 

Evidence  of  Influence  of  Vaccination  Against  Attacks  of  Smallpox. 
— Thus  far  figures  have  been  cited  to  prove  that  vaccination  lessens 
the  fatality  of  smallpox.  It  has  been  shown  that  the  death  rate  of 
smallpox  among  the  vaccinated  is  decidedly  lower  than  among  the 
unvaccinated,  and  that  the  relative  mortality  of  smallpox  among  a 
vaccinated  population  is  strikingly  less  than  among  an  unvaccinated 
one.  It  remains  to  present  evidence  of  the  influence  of  vaccination  in 
the  attack  rate  of  smallpox.  The  British  Royal  Commission  on 
Vaccination  gives  the  following  census  concerning  the  epidemic  in 
Sheffield: 

Sheffield  Attack  Eate. 

Vaccinated  population    ....  268,397  Unvaccinated  population  ....  5715 

Attacked  by  smallpox    ....      4,151  Attacked  by  smallpox       ....  552 

Per  cent 1.55                            Per  cent 9.7 

Vaccinated  children  under  10  years     .    68,236  Unvaccinated  children  under  10  years    .  2259 

Attacked  by  smallpox     ....         353  Attacked  by  smallpox        ....  228 

Per  cent.       .       .       .       .0.5                              Per  cent 10.1 

Vaccinated  persons  10  yrs.  and  upward  196,905  Unvaccinated  persons  10  yrs.  and  upward  3429 

Attacked  by  smallpox    ....      3,774  Attacked  by  smallpox        ....  322 

Per  cent 1.9                                Per  cent 9.4 


120    RELATIONSHIP  OF  COWPOX  OR  VACCINIA  TO  SMALLPOX 

It  is  seen  from  the  above  figures  that  the  attack  rate  among  vaccinated 
children  under  the  age  of  ten  years  was  only  h  per  cent.,  as  compared  with 
10.1  per  cent,  among  the  unvaccinated.  Over  the  age  of  ten  the  attack 
rate  among  the  vaccinated  was  1.9  per  cent.,  and  among  the  unvaccinated 
9.4  per  cent.  ■ 

The  following  table,  which  presents  the  figures  of  five  recent  epidemics, 
gives  results  which  are  remarkably  uniform: 

Attack  rate  under  10  years.  Attack  rate  over  10  years.' 


Vaccinated. 

Unvaccinated. 

Vaccinated. 

Unvaccinated. 

Sheffield 

.      7.9 

67.6 

28.3 

53.6 

Warrington  . 

.      4.4- 

54.5 

29.9 

57.6 

Dewsbury     . 

.    10.2 

50.8 

27.7 

53.4 

Leicester 

.      2.5 

35.3 

22.2 

47.6 

Gloucester    . 

.      8.8 

46.3 

32.2 

50.0 

It  is  evident  from  the  above  comparisons  that  the  lessened  liability 
to  attack  among  the  vaccinated  as  compared  with  the  unvaccinated  is 
much  more  conspicuous  among  children  under  ten  years  of  age  than 
in  a  more  advanced  period  of  life. 

Attack  Rate  in  Invaded  Houses. — In  Sheffield,  of  18,020  vaccinated 
persons  of  all  ages  living  in  infected  houses,  4151,  or  23  per  cent.,  were 
attacked.  Of  736  unvaccinated  persons  under  the  same  conditions, 
552,  or  75  per  cent.,  were  attacked.  When  children  under  ten  years 
are  alone  considered,  the  results  are  remarkable.  Of  4493  vaccinated 
children  in  infected  houses,  353,  or  7.8  per  cent.,  were  attacked;  of  263 
unvaccinated  children,  228,  or  86.9  per  cent.,  were  attacked.  Ten  out 
of  eleven  of  the  vaccinated  children  escaped,  while  but  one  out  of  eight 
of  the  unvaccinated  children  failed  to  take  the  disease. 

Similar  ratios  were  noted  in  the  epidemics  in  Leicester,  Dewsbury, 
and  Gloucester. 

REVACCINATION  STATISTICS. 

It  is  a  well-known  fact  that  the  protection  conferred  by  vaccination 
against  smallpox  becomes  impaired  in  the  course  of  time  and  may, 
indeed,  be  lost  entirely.  The  protection,  however,  may  be  restored  by 
a  second  vaccination,  and  in  the  majority  of  individuals  such  revaccina- 
tion  will  protect  against  smallpox  for  life. 

It  is,  of  course,  understood  that  a  person  upon  whom  an  unsuccessful 
revaccination  has  been  performed  is  not  revaccinated.  Revaccination 
means  a  second  attack  of  vaccinia  and  not  merely  the  rubbing  of  virus 
into  the  skin.  The  failure  of  a  secondary  vaccination  does  not  neces- 
sarily indicate  an  immunity  against  vaccinia  and  variola,  but  may  be 
due  to  faulty  virus  or  technique;  or  the  subject  may  be  for  a  time  immune 
and  later  redevelop  a  susceptibility  to  both  infections. 

We  have  learned  that  vaccination  lessens  both  the  incidence  and  the 
mortality  of  smallpox.  Successfully  revaccinated  persons  are  attacked 
by  smallpox  much  less  frequently  than  those  once  vaccinated,  and  the 
mortality  rate  is  further  reduced.  In  proof  of  this  proposition  the 
following  statistical  evidence  gathered  by  the  British  Royal  Commission 
on  vaccination  is  presented. 


REVAOCINATION  HTA  T/ST/CS  ]  21 

During  the  cpidcniic  of  smallpox  in  Shrljlchl  in  ISS7  (hero  were,  in 
the  town  ()4,4;il  i-cviicciiiiilcd  pcisoiis.  Of  this  iminhcr  27  were  jittafked 
by  srnall})ox,  with  I  death.  Criiis  tnan  had  heen  revueeiiiated  eij^hteen 
years  previously,  in  ISd*).)  The  <tll<irh  rair  of  the  revjieeinated  was, 
therefore,  0.04  per  e(Mit. 

The  attaek  rate  of  vaccinated  |)eis()ns  over  the  ai^e  of  ten,  as  enumer- 
ated in  the  census,  was  l.i)  j)er  cent.,  and  of  the  un\a(cinat(d  persons 
of  the  same  age  j)erio(l  \)A  j)er  cent. 

In  Leicester,  during  the  epidemic  of  IS92-93,  in  a  group  of  \'4'4  houses 
with  842  inmates,  141  persons  were  attacked;  among  84  revaccinated 
inmates  hut  1  was  attacked.  In  another  group  of  fK)  houses  there 
were  392  inmates,  of  whom  170  were  attacked;  among. 31  revaccinated 
persons  5  contracted  the  disease. 

In  the  first  group  the  attack  rate  among  the  revaccinated  was  1.1  per 
cent.,  as  against  14. G  per  cent,  in  the  entire  vaccinated  class.  In  the 
second  group  of  houses,  which  were  evidently  more  intensely  infected, 
the  attack  rate  among  the  revaccinated  was  16.1  per  cent.,  among  the 
vaccinated  35.3  per  cent.,  and  among  the  unvaccinated  59.6  per  cent. 

In  London  in  1892-93  there  were  108  attacks  in  revaccinated  persons, 
of  which  101  were  mild  and  7  severe.  In  this  class  there  were  4  deaths, 
showing  a  mortality  of  3.7  per  cent.  Among  vaccinated  persons  over 
ten  the  mortality  was  4.2  per  cent,  and  among  the  unvaccinated  at  this 
age  period  20.9  per  cent. 

In  Warrington  in  1892-93  there  were  64  revaccinated  persons  in  the 
invaded  houses;  of  these  8,  or  12.5  per  cent.,  were  attacked.  The 
percentage  of  vaccinated  inmates  attacked  was  29.9  per  cent,  and 
unvaccinated  56.0  per  cent.  There  were  41  inmates  who  had  pre- 
viously had  smallpox;  of  this  number  5,  or  12.1  per  cent.,  were 
attacked.  There  were  no  deaths  among  the  revaccinated  or  among 
those  suffering  a  second  attack  of  smallpox. 

The  above  evidence  concerns  comparatively  recent  epidemics.  Re- 
vaccination  was  practised  at  an  early  date  in  some  of  the  armies  of  the 
European  countries,  particularly  among  the  Wiirteniberg  troops  (1833). 
Heim  says  that  in  five  years  there  occurred,  among  14,384  revaccinated 
soldiers  in  Wiirteniberg,  only  one  instance  of  varioloid,  and  among  30,000 
revaccinated  persons  in  civil  life  only  two  cases,  although  during  this 
time  smallpox  had  prevailed  in  344  localities  and  had  produced  1674 
cases  of  smallpox  among  the  not  revaccinated  and  in  part  not  vaccinated 
population  of  363,298. 

In  the  Baden  army  between  1840  and  1868,  according  to  Kussmaul, 
there  were  performed  100,546  revaccinations,  of  which  40,040,  or  39.8 
per  cent.,  were  successful.  During  this  period  of  thirty-nine  years  there 
occurred  in  the  army  359  cases  of  smallpox.  Of  this  number  only  34 
were  in  the  successfully  revaccinated,  while  325  were  in  the  non-vacci- 
nated, or,  at  least,  in  the  unsuccessfully  revaccinated. 

Value  of  Revaccination  as  Illustrated  in  the  Comparative  Small- 
pox Losses  of  the  French  and  German  Armies  in  1870. — The  entire 
German  field  armv,  which  numbered  over  a  million  soldiers,  although 


122    RELATIONSHIP  OF  COWPOX  OR  VACCINIA  TO  SMALLPOX 

exposed  to  a  raging  smallpox  epidemic  in  France,  lost  by  death  from 
this  disease  297  men;  the  French  army,  on  the  other  hand,  suffered 
the  enormous  loss  of  23,469  men  from  smallpox.  (It  will  presently  be 
shown  that  the  German  troops  were  -well  vaccinated  and  the  French 
soldiers  poorly  vaccinated.) 

The  mortality  rate  from  smallpox  of  the  German  soldiers  in  the  field 
was  5.97  per  cent.  Of  the  stationary  or  immobile  German  troops  3472 
were  attacked,  of  whom  162  died,  giving  a  mortality  rate  of  4.6  per  cent. 
The  aggregate  number  of  German  soldiers  attacked,  including  those 
in  the  field  and  the  stationary  troops,  was  8463,  of  whom  459,  or  5.42 
per  cent.,  died. 

The  number  of  cases  in  the  French  army  is  not  known,  but  the  death 
rate  was  forty-nine  times  greater  than  in  the  German  army. 

Moreover,  the  death  rate  of  smallpox  in  the  German  army  compares 
very  favorably  with  the  death  rate  of  the  civil  population  of  Germany. 
In  the  entire  army,  stationary  and  in  the  field,  there  were  459  deaths 
from  smallpox;  in  the  Prussian  kingdom  in  1871  there  were  59,839 
deaths  from  the  same  disease.  Still  more  striking  is  the  comparison  of 
the  death  rate  between  the  army  and  the  inhabitants  of  Berlin.  In  this 
city  of  826,341  population,  a  much  smaller  number  than  that  comprising 
the  army,  the  deaths  from  smallpox  were  5508. 

It  is  known  that  the  Prussian  army^  was  well  vaccinated  up  to  the 
time  of  the  war,  when  the  vaccine  supply  became  insufficient.  Nearly 
all  of  the  soldiers  of  the  German  army  had  been  vaccinated  in  childhood 
and  again  upon  entrance  into  the  army,  for  that  custom  had  been 
enforced  for  a  number  of  years. 

The  French  army,  on  the  other  hand,  was  poorly  vaccinated.  From 
1832  to  1859,  smallpox  caused  39  per  cent,  of  all  deaths  in  the  French 
army.  In  1857  an  order  was  issued  that  all  recruits  be  vaccinated  with- 
out regard  to  the  presence  of  previous  scars,  and  the  smallpox  deaths 
during  1862-72  fell  to  19  per  cent.,  exclusive  of  the  year  of  the  war. 
It  is  evident,  however,  that  vaccination  was  only  partially  practised, 
for  official  record  shows  that  in  1866,  of  45,064  recruits  but  33,513  were 
vaccinated;  in  1868,  of  82,203  recruits  only  47,324  were  vaccinated,  and 
in  1869,  of  115,876  recruits  only  54,720  were  vaccinated;  in  other  words, 
in  1869,  61,156,  or  over  half  the  recruits,  were  not  vaccinated  on  entrance 
into  the  army.  Furthermore,  a  large  proportion  of  the  vaccinations 
performed  were  without  result;  of  first  vaccinations  51  to  63  per  cent, 
failed,  and  on  repetition  66  per  cent,  failed. 

That  locality  did  not  cause  the  discrepancy  in  the  death  rate  of  the 
French  and  German  soldiers  is  shown  by  the  fact  that  the  smallpox 
mortality  among  the  French  prisoners  on  German  soil  was  1963,  while 
the  entire  German  army  on  German  soil  lost  but  162  men. 

The  remarkable  results  of  vaccination  and  revaccination  in  the  German 
army,  particularly  when  compared  with  those  in  the  French  army  and 
with  the  civil  population  of  Germany,  led  to  the  adoption  by  the  German 

1  Edwardes,  loc.  cit. 


/.'/';  VA  aaiNA  tion  sta  risrics 


123 


o'ovcniiTKMit  of  a,  law  inii,kiii<;'  viU'c-iruilioii  and  rc\  acciiuitioii  <-oiii|)ul.Sf>ry. 
This  was  passed  A|)ril  S,  IS74,  and  went  into  cH'cct  on  April  I,  JSyr;. 

Its  essential  provisions  an;  as  follows:  Every  eliild  nnist  be  vaeeinated 
before  the  expiration  of  the  first  year  of  its  life,  unless  it  has  had  small- 
pox or  unless  some  physical  disability  exists;  in  the  latter  event  the 
va(;einati()n  is  undertaken  within  one  year  of  the  removal  of  the  existing 
disability.  Every  ])U])il  of  a  ])iiblie  or  private  educational  institution 
must  be  vaccinated  between  the  age  of  thirteen  and  fourteen  years, 
unless  there  is  medical  proof  that  he  has  had  an  attack  of  smallpox 
within  five  years  or  has  been  successfully  vaccinated  within  that  time. 

Parents,  caretakers,  guardians,  or  heads  of  schools  who  fail  to  comply 
with  the  law  are  subject  to  fine  or  imprisonment.  Vaccination  must 
be  performed  only  by  physicians,  and  anyone  vaccinating  illegally  is 
punished  by  a  fine  not  exceeding  150  marks  or  imprisonment  not 
exceeding  fourteen  days. 


Fig. 18 
PRUSSIA,  1847-1897.      ^ 

SMALL-POX  DEATHS  PER  MILLION  OF  POPULATION. 


AUSTRIA,   1847-1.897. 

SMALL-POX  DEATHS  PER  MILLION  OF  POPULATION. 


Tables  showing  the  decline  of  smallpox  in  Germany  after  the  enaction  of  compulsory  vaccination 
in  1874;  smallpox  mortality  is  compared  with  that  of  Austria. 


The  Results  of  the  German  Compulsory  Vaccination  Law. — If 

there  was  in  existence  no  other  statistical  evidence  of  the  efficacy  of  vacci- 
nation and  revaccination,  the  history  of  smallpox  in  Germany  since 
1875  would  be  all  sufficient  testimony. 

From  1816  to  1870  the  annual  mortality  from  smallpox  in  Prussia 
varied  from  7.32  to  62.0  per  100,000  of  population.  This  death  rate 
was  small  compared  with  the  prevaccination  periods. 

During  the  disastrous  pandemic  of  1871-72  the  rate  was  243.2  and 
262.67,  respectively.     After  the  law  of  1875  went  into  effect  the  annual 


124    RELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 

mortality  in  Prussia  fell  so  that  between  1875  and  1886  the  average 
yearly  mortahty  per  100,000  of  population  was  1.91,  the  maximum 
reaching  3.6  (in  1877). 

On  the  other  hand,  in  Austria,  where  the  lax  vaccination  and  revacci- 
nation  requirements  remained  unchanged,  the  mortality  rate  from  small- 
pox during  about  the  same  period  (1875  to  1884)  increased,  varying 
between  39.28  (1876)  and  94.79  in  1882.     (See  Fig.  18.) 

The  results  of  the  German  vaccination  law  in  the  principal  states  of 
the  Empire  are  given  in  the  following  table: 

The  Results  of  the  Geemak  VAcciNATioisr  Law,  1874. 
(Smallpox  deaths  per  million  living. ) 


Year. 

Prussia. 

Bavaria. 

Wtirtemberg. 

German 
Empire. 

Contrast 

Austria. 

1866 

620 

120 

133 

...1 

368 

1867 

432 

250 

63 

484 

1868 

188 

190 

19 

370 

1869 

194 

101 

74 

374 

1870 

175 

75 

293 

293 

1871 

2432 

1045 

1130 

383 

1872 

2624 

611 

637 

1866 

1873 

356 

176 

30 

3094 

1874 

95 

47 

3 

1725 

2.  Since  1874. 

1875 

36 

17 

3 

576 

1876 

31 

13 

1 

406 

1877 

3.4 

17 

2 

555 

1878 

7.1 

13 

0 

631 

1879 

12.6 

5 

0 

534 

1880 

26 

12 

5.6 

674 

1881 

36.2 

15 

3.6 

807 

1882 

36.4 

12 

6.6 

947 

1883 

19.6 

6 

35.2 

596 

1884 

14.4 

1 

11.6 

530 

1885 

14 

3 

0 

600 

1886 

4.9 

1 

1 

4.2 

400 

1887 

5 

1.8 

0 

3.5 

417 

1888 

2.9 

3.8 

0.5 

2.3 

615 

1889 

5.4 

5.2 

0 

4.1 

537 

1890 

1.2 

1.5 

0 

1.2 

249 

1891 

1.2 

1.2 

0 

1.0 

287 

1892 

3 

0.5 

0 

2.1 

256 

1893 

4.4 

0.7 

1 

3.1 

244 

1894 

2.5 

0.3 

0 

1.7 

105 

1895 

0.8 

0.2 

0 

0.5 

49 

1896 

0.2 

0.2 

0 

0.2 

36 

1897 

0.2 

0 

0 

0.1 

61 

1898 

0.4 

0.3 

0 

0.3 

1899 

0.5 

The  remarkable  results  of  compulsory  vaccination  and  revaccination 
in  Germany  are  perhaps  the  more  striking  when  the  mortality  rate  of 
smallpox  in  Gerrnan  cities  is  compared  with  cities  of  other  countries. 
After  compulsory  revaccination  in  1875  the  average  annual  death  rate 
from  variola  from  1875  to  1886  in  the  followins"  cities  was  as  follows: 


1  No  statistics. 


VA  C(,'JNA  TION  STA  TISTICS  125 

Death  Ratk  i^'kom  SMAiii.i'ox  i-ioii  100,000  ov  I'oimjla'iion. 

Uennai)  (.'ities.  Oilier  CilioK. 

Berlin        ....  I.IO  iicrsons.  Pariw        ....    2C>.'i\  \>trtv>iin. 

Hamburg  .        .        .  0.74        "  .St.  I'cterwburfj        .        .    3.'). 82        " 

Breslau     ....  1.11        "  Vioiina   ....    M.'M        " 

Dresden    ....  1.03        "  fragile    ....  147.90        " 

There  is  hut  one  e.xphuiation  for  the  inarvcloiisly  low  dc'itli  nitf  iti 
the  German  cities  as  compared  with  other  coiiliiiciilnl  (•(■ii(i«v^;  ilmt 
explanation  is  carrjvl  and  universal  vaccination  and  rcracriiKilion. 

A  comparison  of  total  .smallpox  aUaclcs  in  the  (jcrman,  Frciicli,  aiul 
Austrian  armies  aft(M-  1X75  is  e((ua,lly  instructive: 

German  army    (1875-1887) 148  men. 

French  army    (1875-1881) 5,605      " 

Austrian  army  (1875-1886) 10,238      " 

In  the  German  army,  despite  greater  numbers  and  a  longer  period 
of  time,  the  smallpox  attacks  were  enormously  less  than  in  the  French 
and  Austrian  armies. 

Since  the  law  of  1875  went  into  effect  in  Germany,  there  have  been  no 
epidemics  of  smallpox  in  that  country.  The  smallpox  is  frequently 
introduced  by  foreigners,  particularly  on  the  frontiers,  but  the  disea.se 
can  find  no  foothold.  In  1899  there  occurred  in  the  German  Empire, 
among  54,000,000  people,  28  deaths  from  smallpox;  these  occurred 
in  twenty-one  different  districts,  the  largest  number  in  any  one  district 
being  3.    Not  a  case  occurred  in  a  large  town. 

Kiibler^  in  speaking  of  the  importation  of  smallpox  into  Germany, 
says:  "Among  the  fatal  cases  there  were  many  who  had  come  from 
foreign  countries;  in  the  interior  of  the  Empire  aliens,  chiefly  Russian- 
Polish  laborers,  constituted  a  large  percentage  of  those  who  contracted 
the  disease.  The  annual  recurrence  of  the  pestilence  among  these 
people  has  recently  necessitated  a  regulation  that  workmen  before  being 
admitted  to  employment  within  the  realms  must  produce  proof  of 
successful  vaccination  or  recovery  from  an  attack  of  smallpox,  and  in 
case  they  were  unable  to  do  so  they  must  submit  to  vaccination." 

The  following  figures  indicate  the  prevalence  of  smallpox  on  the 
German  frontier  as  compared  with  the  interior. 

The  mortality  from  smallpox  in  Germany  from  1886  to  1889  was: 

At  the  Frontier.  In  the  Interior. 

1886 UO  cases.  45  cases. 

1887 119      "  49      '• 

1888 94      "  16      " 

1889 188      "  12      " 

In  1897  there  were  but  five  deaths  from  smallpox  in  the  entire  German 
Empire  (54,000,000  population). 

Furthermore,  for  a  period  of  th  irtcen  years  in  a  population  comprising 
two-fifths  of  the  total  inhabitants  of  Germany,  there  were  only  five 
instances  of  death  from  smallpox  in  successfully  rcvaccinated  persons. 

1  Geschichte  der  Impfung  und  Blattern,  1901. 


126     RELATIONSHIP  OF  COWPOX  OR   VACCINIA  TO  SMALLPOX 

Germany  has  taught  the  world  how  to  utihze  Jenner's  great  discovery 
SO  as  to  exterminate  smallpox. 

The  German  Vaccination  Commission  of  1884,  referring  to  the  influ- 
ence of  the  compulsory  vaccination  law,  says: 

"Previously  to  1871  smallpox  mortality  in  Austria  behaved  much 
like  that  of  Prussia,  though  higher  on  the  whole.  The  great  epidemic 
of  1872-74  was  more  fatal  and  lasted  longer  than  in  Prussia.  During 
the  next  two  years  the  mortality  fell,  as  usual  after  epidemics.  Here 
the  influence  of  the  epidemic  in  lowering  the  mortality  ceases,  and  the 
latter  rises  at  once  to  its  old  figures,  viz.,  as  before  the  epidemic,  and 
even  higher,  and  this  rise  was  not  merely  temporary. 

"The  remarkable  and  persistent  decline  in  Prussia  since  1875  can 
only  be  due  to  the  vaccination  law  of  1874,  because  all  other  conditions 
remain  the  same  in  the  two  countries.  The  only  difference  is  that  in 
Prussia  the  revaccination  of  all  school-children  at  the  age  of  twelve 
years  was  made  compulsory  in  1874." 

The  Board  of  Health  of  Berlin  has  prepared  tables  comparing  the 
number  of  deaths  occurring  between  the  years  1886  and  1889  in  countries 
having  compulsory  vaccination,  and  those  without  such  provision: 


Population. 

1886. 

Smallpoj 

1887. 

c  deaths. 
1888. 

1889. 

Average 
of 

deaths. 

Average 

per 
million 
of  popu- 
lation. 

>.  .  f  Sweden,  4,746,465  . 
^f  Ireland,  4,808,728  . 
B<'3  -1  Scotland,  4,013,029  . 
a§  Germany,  47,923,735  . 
5  **    l  England,        28,247,151    . 

Switzerland,   2,922,430    . 

Belgium,         5,940,365    . 

Russia,           92,822,470    . 

Austria,          23,000,000    . 

Italy,              29,717,982    . 

Spain,             11,864,000    . 

1 

2 

24 

197 

275 

182 

1,213 

16,938 

8,794 

1 

5 

14 

17 

168 

505 

14 

610 

25,884 

9,591 

16,249 

1 

9 

3 

0 

112 

1,026 

17 

865 

1 

2 

0 

6 

200 

28 

3 

1,212 

1 

4 

5 

12 

169 

458 

54 

975 

21,411 

11,220 

15,925 

11,425 

1    1 
1     1 
3     1- 
3.5  1 
16    J 
18.5 
164 
231 

14,138 
18,110 
14,378 

12,358 
13,416 

8,472 

510 
536 

1 

963 

But  a  glance  is  necessary  to  show  the  striking  difference  between  the 
number  of  deaths  in  those  countries  having  compulsory  vaccination  and 
those  in  which  there  is  no  such  measure.  The  average  deaths  per 
million  in  the  compulsory  vaccination  countries  is  eighty  tiTues  less  than 
in  the  others.  Furthermore,  England  is  the  least  vaccinated  of  the 
compulsory  countries  and  her  death  rate  is  the  highest  among  these. 

The  Imperial  Board  of  Health  of  the  German  Empire  gives  the 
frequency  of  smallpox  in  various  European  countries  between  1893  and 
1897  inclusive,  a  period  of  five  years.^ 


1  No  statistics. 


"  Quoted  by  Kiibler,  loc.  cit. 


VA  (J(UNA  TION  ST  A  'I'lS'l'IdS 


Vll 


TlfE   FllEQUfiNCY   01''    SmALM'OX    FN     EUROt'KAN    SlATKH     HIO'IWKKN     IHD.'i-lSO? 

rNCI.UHfVK   (5    YKARS). 


Average  yearly 

Actual 

Country. 

I'opulation. 
52,042,282 

mortality  in 

every  million 

fjopulatlon. 

1.1 

number 

Hmallpux 

deatOH. 

YearH. 

Germanv 

287 

5 

Denmark 

79»,3:)6 

0.5 

2 

6 

Sweden 

4,894,790 

2.1 

41 

4 

Norway 

2,045,900 

0.6 

5 

4 

England  and  Wales 

30,389,524 

20.2 

8,066 

5 

Scotland 

4,155,880 

12.3 

256 

5 

Ireland 

4,580,5.55 

9.9 

226 

5 

Switzerland 

3,032,901 

5.1 

78 

5 

Netherlands 

4,707,249 

38.7 

929 

5 

Belgium 

6,419,498 

99.9 

3,208 

5 

French  States 

8,253,079 

90.2 

3,721 

5 

Russian  Empire  including  Asiatic  Russia 

118,950,400 

463.  2 

275,502 

5 

Austria 

23,000,000 

99.1 

11,799 

5 

Italy       

31,007,422 

72.7 

11,278 

5 

Spain 

10,596,649 

563.  4 

23,881 

4 

Hungary 

18,234,916 

134. 3 

12,241 

5 

Here,  again,  the  countries  which  during  this  period  have  the  most 
stringent  vaccination  laws  suffer  the  least  smallpox,  namely,  Germany, 
Denmark,  Sweden  and  Norway. 

In  well-vaccinated  Germany,  but  one  person  a  year  in  every  million 
died  of  smallpox. 

In  England  and  Wales,  where  vaccination  is  generally  but  not  univer- 
sally practised,  20  persons  per  million  died  each  year. 

In  Austria,  where  the  vaccination  laws  are  poorly  enforced,  99  persons 
per  million  died  each  year. 

It  is,  indeed,  quite  possible  to  know  to  what  extent  vaccination  is 
practised  in  the  various  countries  by  noting  the  mortality  from  small- 
pox. 

There  is  an  inverse  proportion  between  these  factors.  It  is  evident, 
therefore,  that  in  Spain  and  in  Russia  (including  Asiatic  Russia)  vacci- 
nation must  be  greatly  neglected. 

The  tables  teach  another  lesson,  namely,  that  without  vaccination 
smallpox  is  still  to  be  regarded  as  a  dread  scourge,  as  a  great  destroyer 
of  human  life.  For  in  the  five  years  from  1893  to  1897,  in  the  sixteen 
countries  mentioned,  346,520  lives  were  sacrificed  to  smallpox;  of  this 
number  Russia  lost  275,502.  These  figures  are  the  more  terrible  when 
it  is  recognized  that  these  lives  might  have  been  saved  by  the  application 
of  a  prophylactic  measure  within  the  reach  of  all. 

Immunity  of  Physicians  and  Nurses  in  Smallpox  Hospitals. — If  it 
can  be  demonstrated  that  physicians  and  nurses  in  smallpox  hospitals 
are  protected  by  vaccination,  this  must  be  regarded  as  a  crucial  test. 
For  if  these  persons,  living  in  the  same  atmosphere  with  scores  or  hundreds 
of  smallpox  patients,  breathing  in  their  very  exhalations,  are  enabled 
to  escape  the  infection,  it  certainly  should  be  possible  for  others  much 
less  exposed  to  acquire  similar  immunity. 

Experience  shows  that  physicians,  nurses  and  others,  if  recently  success- 
fully vaccinated,  may  live  in  smallpox  hospitals  with  perfect  safety.    The 


128    RELATIONSHIP  OF  COWPOX  OR  VACCINIA  TO  SMALLPOX 

immunity  of  employes  (when  properly  revaccinated)  is  a  uniform 
experience  in  practically  all  smallpox  hospitals. 

In  the  hospitals  of  London,  from  1876-79,  there  were  admitted  11,412 
smallpox  patients  who  had  been  vaccinated  in  infancy,  but  not  a  single 
case  was  known  to  have  occurred  in  a  person  who  had  been  successfully 
revaccinated.  It  was  the  rule  to  revaccinate  all  nurses  and  employes 
before  entering  the  hospital,  and  the  number  thus  employed  amounted 
to  about  1000;  of  these  only  some  half-dozen  took  smallpox,  and  they, 
for  some  cause  or  other,  had  escaped  revaccination. 

Dr.  Marson,^  physician  to  the  Smallpox  Hospital  of  London  for  many 
years,  giving  evidence  in  1871,  stated  that  during  the  preceding  thirty-five 
years  no  nurse  or  servant  at  the  hospital  had  been  attacked  with  smallpox. 
Since  that  period  one  case  only  has  occurred,  and  that  in  an  unrevacci- 
nated  gardener.  Thus,  during  a  period  of  sixty  years  but  one  case  of 
smallpox  has  occurred  among  hundreds  of  persons  who  were  in  the 
closest  contact  with  the  disease.  Dr.  Marson  took  the  precaution  of 
revaccinating  all  persons  before  permitting  them  to  go  on  duty.  Dr. 
Collie,^  whose  experience  is  also  large,  says:  "During  the  epidemic  of 
1871,  out  of  110  smallpox  attendants  at  Homerton,  all  but  2  were 
revaccinated,  and  these  2  took  smallpox." 

At  a  meeting  of  the  German  Vaccination  Commission  (1884)  Dr. 
Eulenburg  related  "that  a  manufacturer  in  Posen  had  all  his  workmen 
vaccinated  except  one,  who  refused.  This  man  alone  of  the  150  took 
smallpox  shortly  afterward  and  died." 

In  1885  a  committee  of  the  Epidemiological  Society  of  London  reported 
that  out  of  1500  attendants  in  smallpox  hospitals,  43  took  smallpox 
and  not  1  of  the  Jj.3  had  been  revaccinated.^ 

"The  experience  of  the  epidemic  of  1876-77  was  of  the  same  kind, 
all  revaccinated  attendants  having  escaped,  while  the  only  one  who  had 
not  been  vaccinated  took  the  disease  and  died  of  it."* 

In  the  epidemic  of  1881  in  London,  of  90  nurses  and  other  attend- 
ants of  the  Atlas  Smallpox  Hospital  Ship,  the  only  person  who  con- 
tracted smallpox  was  a  housemaid  who  had  not  been  revaccinated.^ 

Dr.  T.  F.  Ricketts,*'  the  medical  superintendent  of  the  Smallpox 
Hospital  Ships  on  the  Thames,  shows  that  out  of  1201  persons  in  attend- 
ance on  board  the  smallpox  ships  since  1884,  only  6  contracted  the 
disease,  and  all  recovered.  None  of  these  persons  had  been  successfully 
revaccinated  before  going  on  duty. 

At  the  Southampton  Fever  Hospital  all  persons  employed  during  the 
smallpox  epidemic  of  1893  were  revaccinated  before  going  on  duty,  and, 
although  freely  exposed  to  the  disease,  not  a  single  individual  con- 
tracted smallpox.^ 

According  to  Dr.  Hill,  of  Birmingham,  during  the  epidemic  in  1893 
over  100  persons  were  employed  at  the  City  Smallpox  Hospital,  all  of 

1  E.  J.  Edwardes,  The  Practitioner,  May,  1896.  2  Ibid.,  loc.  cit. 

3  Transactions  of  the  Epidemiological  Society,  vol.  v.,  new  series. 

*  Dr.  Collie,  Quain's  Dictionary  of  Medicine. 

6  Mentioned  by  Ernest  Hart.    Allbutt's  System  of  Medicine. 

6  Report  of  the  Metropolitan  Asylums  Board  for  1892.  '  Hart,  loc.  cit. 


IMMUNITY  OF    Vy\(!(;  I  NAT  HI)  l>ll  YSKHA  NS  A  N  I)   Nl'llSHS     ];>] 

jiot  rcspoiidiiifi;  to  vacciiiiitioii  after  two  or  three  earefiil  trials.  Of  the 
entii'e  niirnher  of  students  one  contra(;te(I  srnalljjox,  anrl  it  was  suhse- 
qiiently  foniul  that  he  had  never  })cen  suecessfiilly  vaccinated. 

Since  the  present  ej)idemi(;  he^an,  al)Out  200  })ersons,  inchjdin^ 
})hysieians,  run-ses,  ward  niaids,  cooks,  hiundresses,  and  the  like,  liave 
been  employed  in  the  smallpox  department,  and  not  one  has  contracted 
the  disease. 

These  facts  are  not  wondered  at  by  those  who  are  familiar  witli 
smallpox;  they  are  anticipated.  P^vidence  of  this  same  nature  has 
accumulated  for  nearly  a  half-century.  P>very  ej)idemic  adds  fresh  data. 
The  innn unity  of  revaccinated  nurses  and  physicians  against  smallpox 
constitutes  testimony  in  favor  of  the  efficacy  of  vaccination  which  is 
irrefutable. 

Further  Direct  Evidence  of  the  Efficacy  of  Vaccination..  Much 
convincing  evidence  of  the  protection  afforded  by  vaccinati(jn  against 
smallpox  never  appears  in  morbidity  or  mortality  statistics.  Every 
physician  who  is  familiar  with  smallpox  can  cite  numerous  instances  of 
such  protection.  Jenner  and  other  early  vaccinators  established  direct 
proof  of  the  virtue  of  vaccination  by  showing  that  smallpox  could  not 
be  given  to  an  individual  recently  successfully  vaccinated. 

Dr.  Jenner  in  1801  wrote:  "Upward  of  6000  persons  have  now  been 
inoculated  with  the  virus  of  cowpox,  and  the  far  greater  part  of  them 
have  since  been  inoculated  with  that  of  smallpox,  and  exposed  to  its 
infection  in  every  rational  way  that  could  be  devised,  without  effect." 
And  Dr.  Woodville,  in  1802,  stated  that  within  two  years  there  were 
vaccinated  at  the  Smallpox  Hospital  7500  persons,  of  whom  about  one- 
half  were  subsequently  inoculated  with  smallpox  matter,  and  in  none 
of  them  did  smallpox  produce  any  effect. 

Smallpox  is  one  of  the  most  highly  contagious  of  all  diseases,  and 
nearly  every  human  being  is  susceptible  to  it;  we  could  cite  scores  of 
instances  of  protection  granted  to  persons  by  vaccination  after  admission 
to  the  Municipal  Hospital.  A  few  examples  which  occurred  during  the 
recent  epidemic  (1901-04)  and  of  wdiich  we  have  notes  will  suffice. 

A  child  of  one  year,  who  had  been  successfully  vaccinated  about  ten 
days  before  admission,  was  sent  to  the  hospital  with  roseola  vaccinosa 
which  had  been  diagnosed  as  variola.  The  child  remained  in  the 
smallpox  wards  about  three  wrecks  and  continued  perfectly  well.  Another 
child,  of  nine  years,  with  exactly  the  same  history,  returned  home 
perfectly  well  after  a  constant  exposure  of  over  three  weeks.  An  un- 
vaccinated  colored  child,  about  tw^o  years  old,  was  brought  into  the 
hospital  with  a  sister  who  was  suffering  from  smallpox.  Immediately 
after  admission  vaccination  was  performed,  and  although  the  child  was 
constantly  exposed  to  the  infection  for  three  weeks  he  did  not  take  the 
disease.  Several  other  children  and  also  some  adults,  who  were  sent 
to  the  hospital  under  erroneous  diagnosis,  were  vaccinated  for  the  first 
time  after  admission  and  were  rendered  absolutely  immime. 

In  every  epidemic  of  smallpox  that  has  occurred  in  Philadelphia 
within  the  past  thirty  years,  instances  have  been  observed  of  whole 


132    BELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 

families  being  removed  to  the  hospital  because  of  an  outbreak  of  the 
disease  in  these  famihes.  In  such  instances  the  unvaccinated  children 
have  suffered  and  often  perished,  while  those  who  were  vaccinated 
remained  perfectly  exempt,  although  living,  eating,  and  sleeping  in  the 
infected  atmosphere  for  several  weeks.  But  we  have  yet  to  see  unvac- 
cinated children  escape  the  disease  under  similar  conditions  of  exposwe. 
Furthermore,  we  have  more  than  once  seen  a  vaccinated  infant  take  its 
daily  supply  of  nourishment  from  the  breast  of  its  mother  who  was 
suffering  from  varioloid,  and  the  infant  continue  as  free  from  smallpox 
as  if  the  disease  were  one  hundred  miles  away  and  the  food  derived 
from  the  most  wholesome  source.  This  is  evidence  of  the  prophylactic 
power  of  vaccination  that  does  not  appear  in  mortality  reports  nor  in 
statistical  records. 

Ravages  of  Smallpox  in  Countries  where  Vaccination  is  Neglected. — 
In  most  of  the  European  countries  and  in  the  United  States  smallpox 
at  the  present  day  is  a  comparatively  rare  disease,  appearing,  as  it  does, 
in  epidemics  at  infrequent  intervals.  Many  physicians  who  have  been 
in  practice  for  fifteen  or  more  years  have  never  encountered  even  a 
single  case  of  this  disease.  In  well-vaccinated  countries  the  epidemics 
are  small  and  of  short  duration.  In  countries,  however,  in  which 
vaccination  is  neglected,  the  epidemics  may  attain  in  extent  and  mor- 
tality the  terrible  numbers  that  were  reached  in  the  days  before  vacci- 
nation. In  the  Russian  Empire,  including  Asiatic  Russia,  there  were 
275,502  deaths  from  smallpox  in  the  five  years  from  1893  to  1898.  In 
Spain,  with  a  population  of  only.ten  and  a  half  million  people,  there  were 
23,881  deaths  from  smallpox  during  this  period.  Hungary  had  12,241 
deaths,  and  Italy  and  Austria  each  over  11,000  deaths.  In  Germany, 
where  there  is  compulsory  vaccination  and  revaccination  the  smallpox 
deaths  during  the  same  five  years  numbered  only  287. 

Dr.  Jeanselme^  is  authority  for  the  statement  that  smallpox  is  still 
a  murderous  disease  in  Indo-China  and  other  parts  of  the  East.  He 
estimates  that  a  quarter  of  the  infantile  population  succumbs  to  this 
disease.  During  times  of  epidemic  recrudescence  the  death  rate  is 
higher  still.  In  1900  Dr.  Jeanselme  saw  the  population  of  the  village 
of  Loos  almost  completely  swept  away  by  smallpox,  a  few  old  people, 
protected  by  a  previous  attack,  being  the  only  survivors. 

Children  under  the  age  of  five  years  furnish  the  greatest  number  of 
victims.  The  Annamites  and  Cambodgians  regard  variola  as  a  necessary 
evil,  and  children  who  have  not  gone  through  it  practically  do  not  count 
as  members  of  the  family.  Vaccination  is  greatly  neglected,  but  inocula- 
tion is  practised.  The  blind  in  Indo-China  are  numerous,  the  loss  of 
vision  in  large  part  being  due  to  smallpox.^ 

The  above  conditions  might  readily  prevail  in  all  countries  if  the 
opponents  of  vaccination  were  successful  with  their  propaganda. 

1  Quoted  in  the  British  Medical  Journal,  August  16,  1902.  2  it,id. 


UNANIMITY  OF  OI'INION  AS  TO    VAI.UK  OF   VAfKJ/NATfON      ];>/.>, 

UNANIMITY  OF  OPINION  AS   TO   THE  VALUE   OF  VACCINATION. 

There  lius  j)rol)ul)ly  never  heeii  in  tlie  history  oF  iiiiiiikiiid  a  ^reat 
discovery  the  acceptance  of  which  some  men  (\'u\  not  (Hspute.  The 
fijreat  truth  which  -lenner  j^ave  to  the  world  offers  no  cxcei^tion  to  this 
general  statenuMit.  There  urc  (hssenters  wlio  do  not  hcheve  in  vacci- 
nation, but  tliey  are  chiefly  to  he  found  outside  of  the  inctheal  |)rofession. 
We  know  of  no  eminent  physician  wito  is  not  conoinced  of  the  efficacy  of 
vaccination;  those  physicians  who  have  had  a  large  practical  experience 
with  smallpox  are  the  most  ardent  advocates  of  vaccination,  for  they 
have  had  the  best  op])()rtunity  of  notiuji;  the  behavior  (;f  vaccinated 
individuals  in  the  presence  of  smallpox.  The  few  physicians  who  are 
found  in  the  ranks  of  the  antivaccinationists  are  usually  men  without 
practical  experience  in  smallpox;  they  argue  with  statistics  (often  wit- 
tingly or  unwittingly  distorted)  and  not  with  facts  derived  from  j)er- 
sonal  observation. 

As  a  prophylactic  remedy  against  smallpox  vaccination  was  generally 
accepted  by  the  medical  profession  at  an  early  date. 

In  1856  the  Medical  Officer  of  the  London  Board  of  Health,  John 
Simon,  sent  circular  letters  to  542  prominent  members  of  the  medical 
profession  in  the  United  Kingdom  and  in  some  of  the  other  European 
countries,  requesting  their  opinions  as  to  the  value  of  vaccination. 
Five  hundred  and  thirty-nine  replies  were  received  and  there  w^as 
absolute  unanimity  as  to  the  efficacy  of  vaccination  as  a  protective 
measure  against  smallpox. 

The  most  distinguished  medical  bodies  in  every  country  have  time  and 
time  again  affirmed  their  confidence  in  the  protective  influence  of 
vaccination,  and  the  most  enlightened  nations  of  the  earth  have  officially 
recognized  its  value  and  have  encouraged  its  practice. 

Thomas  Jeflferson's  appreciation  of  the  value  of  Jenner's  discovery 
may  be  judged  from  the  following  letter  addressed  to  the  discoverer 
of  vaccination: 

MoNTiCELLO,  Virginia,  May  14, 1806. 

Sir  :  I  have  received  a  copy  of  the  evidence  at  large,  respecting  the  discovery  of  the  vaccine 
inoculation,  which  you  have  been  pleased  to  send  me,  and  for  which  I  return  you  many  thanks. 
Having  been  among  the  early  converts  of  this  part  of  the  globe  to  Its  efficacy  I  took  an  early  part 
in  recommending  it  to  my  countrymen,  I  avail  myself  of  this  occasion  to  render  you  my  portion 
of  the  tribute  and  gratitude  due  to  you  from  the  whole  human  family.  Medicine  has  never  before 
produced  any  single  improvement  of  such  utility.  Harvey's  discovery  of  the  circulation  of  the 
blood  was  a  beautiful  addition  to  our  knowledge  of  the  ancient  economy  ;  but  on  a  review  of  the 
practice  of  medicine  before  and  since  that  epoch,  I  do  not  see  any  great  amelioration  which  has 
been  derived  from  that  discovery.  You  have  erased  from  the  calendar  of  human  afflictions  one  of  its 
greatest.  Yours  is  the  comfortable  reflection  that  mankind  can  never  forget  that  you  have  lived  ; 
future  nations  will  know  by  history  onli/ that  the  loathsome  smallpox  has  existed,  and  by  you  has  been 
extirpated.  Accept  the  most  fervent  wishes  for  your  health  and  happiness,  and  assurance  of  the 
greatest  respect  and  consideration. 

Th.  Jkfpkeson. 

Thomas  Jefferson's  prophecy  that  "future  nations  will  know  by 
history  only  that  the  loathsome  smallpox  has  existed"  fails  of  fulfilment 
only  because  vaccination  and  revaccination  are  not  universally  adopted. 


134    RELATIONSHIP  OF  COWPOX  OB  VACCINIA  TO  SMALLPOX 


OPPOSITION  TO  VACCINATION. 

It  is  a  remarkable  fact  that,  despite  one  hundred  years  of  incontrovert- 
ible testimony  of  the  value  of  vaccination,  there  should  still  exist  at  the 
present  day  an  organized  antivaccination  movement.  To  be  sure  the 
active  opponents  of  vaccination  comprise  but  a  very  small  percentage 
of  the  people,  but  their  influence  is  none  the  less  noxious.  Curiously 
enough  the  opposition  to  vaccination  is  most  acute  in  the  very  country 
whence  this  great  discovery  sprang;  this  fact  is  a  sad  commentary  upon 
the  common  sense  of  this  portion  of  the  English  population.  The 
opponents  of  vaccination  include  a  number  of  persons  of  prominence 
in  the  literary  world ;  indeed,  a  large  library  of  antivaccination  literature 
has  gradually  arisen. 

No  great  truth  is  ever  promulgated  that  does  not  meet  with  opposition ; 
the  truth  of  the  value  of  vaccination  has  satisfied  the  pidgment  of  Tnedical- 
men,  but  a  certain  number  of  individuals  outside  of  the  profession 
dissent  therefrom.  These  persons  have,  in  various  countries,  banded 
together  to  antagonize  the  practice  of  vaccination  and  to  oppose  its 
compulsory  enforcement. 

We  prefer  to  look  upon  these  persons  as  misguided  rather  than  regard 
them  in  a  less  charitable  light.  The  evidence  in  favor  of  vaccination  is 
so  strong  and  irrefutable  that  an  unbiased  student  of  the  subject  can 
arrive  at  but  one  conclusion.  There  is  no  truth  more  clearly  established 
than  that  vaccination  and  revaccination  properly  performed  protect 
against  smallpox.  And  yet  some  antivaccinationists  persist  in  mis- 
interpreting facts  and  figures  with  a  view  of  discrediting  vaccination; 
this  is  often  so  patent  as  to  clearly  establish  the  effort  as  wilful  perversion. 
Antivaccination  propaganda  have  caused  many  innocent  victims  to  he 
consigned  by  smallpox  to  a  premature  grave. 

There  is  but  one  rational  argument  for  opposition  to  vaccination, 
namely,  that  the  practice  of  this  measure  is  not  entirely  devoid  of  some 
danger.  But  the  danger  is  so  slight  in  any  individual  instance  that  it 
is  almost  a  negligible  quantity.  No  human  act  is  completely  unattended 
with  risk.  When  the  rare  instances  of  death  following  vaccination  are 
compared  with  the  frightful  slaughter  of  thousands  by  smallpox  before 
the  days  of  vaccination,  and  even  at  the  present  day  in  countries 
where  vaccination  is  neglected,  the  benefits  of  Jenner's  God-given 
discovery  may  be  appreciated. 


CHAPTER    I  II. 

THE  VARIOLOUS  DISEASES  OF  LOWER  ANIMALS. 

A  NUMBER  of  domesticated  animals  ap[)ear  to  l)c  siiscc|)til)I<'  to  pock 
diseases  which  are  more  or  less  closely  allied  to  human  smallpox.  Those 
affections  are,  by  reason  of  difference  in  behavior,  divisible  into  two 
natural  grou})S.  The  diseases  comprised  in  the  first  <(roup  are  communi- 
cable throufi;li  the  atmosphere;  they  are  accompanied  by  a  generalized 
eruption,  and  may  be  regarded  as  death-dealing  pestilences;  in  this 
class  are  to  be  included  human  variola  and  sheeppox.  In  the  second 
group  the  diseases  are  only  capable  of  transmission  by  inoculation 
(accidental  or  intentional);  the  eruption  is  usually  limited  to  the  sites 
of  inoculation,  and  death  rarely  takes  place.  In  the  second  group 
belong  cowpox,  horsepox,  apepox,  and  other  domestic  animal  pock 
diseases  presently  to  be  described. 

Jenner  was  firmly  of  the  belief  that  many  of  the  common  farm  animals 
were  subject  to  eruptive  diseases  allied  to  variola.  He  says:^  "Our 
domestic  animals  are  subject  to  a  variety  of  eruptive  diseases — the 
horse,  the  cow,  the  sheep,  the  hog,  the  dog,  and  many  others.  Even 
poultry  come  in  for  their  share.  Again,  there  certainly  must  be  a  reason 
why  the  term  chicken  is  annexed  to  a  species  of  pock  which  infests  the 
human  skin.  In  the  province  of  Bengal  the  poultry  are  subject  to 
eruptions  like  the  smallpox,  which  becomes  epidemic  and  kills  them  by 
the  hundreds." 

Dr.  Baron^  says:  "It  seems  certain  that  there  are,  at  least,  four 
animals— namely,  the  horse,  the  cow,  the  sheep  and  the  goat — which  are 
aft'ected  with  a  disorder  communicable  to  man,  and  capable  of  securing 
him  from  what  appears  to  be  a  malignant  form  of  the  same  disease. 
It  is,  moreover,  proved  that  other  animals  may  take  the  vaccine  disease 
by  inoculation,  and  that  matter  taken  from  pustules  so  produced  affords 
the  genuine  cowpox  in  man.  The  animals  on  which  these  experiments 
have  been  tried  are  the  dog,  the  goat,  the  she-ass,  and  the  sheep.  The 
fact  as  regards  the  dog  was  ascertained  by  Dr.  Jenner." 

Indeed,  Jenner  alleges  to  have  found  dogs  very  susceptible  of  the 
variolse  vaccinae;  he  believed  that  an  attack  of  this  disease  rendered 
the  dog  immune  against  the  distemper. 

Smallpox  of  Sheep. — Sheeppox,  variola  ovina,  or  clavelee,  is  an  acute 
contagious  and  epizootic  disease  characterized  by  SNanptoms  closely 
simulating  the  manifestations  of  variola  in  the  human  subject. 

Variola  ovina  is  supposed  to  have  arisen  in  Asia,  and,  like  smallpox, 
to  have  extended  thence  to  the  continent  of  Europe.    Various  countries 

1  Manuscript  of  Jenner,  quoted  by  Baron.  -  Life  of  Jenner,  p.  243. 


136  THE  VARIOLOUS  DISEASES  OF  LOWER  ANIMALS 

have,  from  time  to  time,  experienced  devastating  epidemics  which  have 
greatly  interfered  with  the  sheep-growing  industry. 

The  period  of  incubation  of  the  disease  is  somewhat  variable,  but 
is  ordinarily  between  nine  and  twelve  days.  It  is  stated  that  sheep  may 
now  and  then- remain  unaffected  for  a  period  of  one  or  even  two  months, 
although  intimately  exposed  to  the  contagion  of  the  disease.  Some 
Continental  observers  state  that  the  eruption  is  preceded  by  two  or 
three  days  of  fever,  but  Simonds  and  other  English  writers  affirm  that 
in  their  experience  they  have  never  noted  any  illness  prior  to  the  appear- 
ance of  the  eruption. 

At  this  time  the  infected  sheep  separates  himself  from  his  fellows, 
looks  weak  and  dejected,  lies  down  and  refuses  food,  although  he  will 
drink  water  freely.  The  breathing  is  quick  and  short  and  the  heart 
beats  accelerated.  The  conjunctivae  are  reddened,  the  lids  swollen,  and 
the  tears  trickle  down  the  face.  A  mucous  discharge  issues  from  the 
nose  and  tends  to  block  the  nostrils.  These  symptoms  begin  synchro- 
nously with  the  eruption  and  continue  until  vesiculation  begins,  when 
there  is  commonly  an  abatement  of  these  manifestations. 

The  eruption  appears  as  florid-red  papules,  which  are  firm  and 
unyielding  to  the  touch.  These  are  usually  observed  first  on  the  inner 
side  of  the  extremities,  and  on  the  cheeks  and  lips,  where  the  skin  is 
hairy,  but  not  covered  with  wool.  Nude  portions  of  the  body,  such  as 
the  prepuce,  labia,  anus,  and  inferior  surface  of  the  tail  may  be  simul- 
taneously attacked.  The  eruption  rapidly  spreads  over  the  entire 
integument,  manifesting  itself  either  in  a  discrete  or  confluent  form. 
In  certain  species  the  face  is  profusely  involved,  in  which  case  the 
disease  proves  extremely  fatal. 

The  duration  of  the  papular  stage  may  vary  between  two  and  six 
days,  averaging  three  in  the  majority  of  cases;  this  stage  is  somewhat 
protracted  in  confluent  cases.  The  reddish  papules  become  gradually 
converted  into  whitish  vesicles  containing  a  limpid  fluid.  Many  of  the 
vesicles  are  small,  and  nearly  all  are  unilocular,  contrasting  in  this 
respect  with  the  multilocular  character  of  the  vesicles  in  human  variola. 
The  transformation  of  the  papules  into  vesicles  is  not  uniform,  some 
undergoing  this  change  a  day  or  two  after  others,  while  some  papules 
may  disappear  without  vesiculating  at  all.  The  vesicles  are  not  sur- 
rounded by  an  areola  at  an  early  stage,  but  only  after  they  have  fully 
matured.  In  the  perfectly  formed  vesicle  of  sheeppox  a  central  depres- 
sion may  be  seen,  but  this  is  far  from  being  constant. 

The  duration  of  the  vesicular  stage  is  variable.  In  the  milder  cases 
the  eruption  may  not  progress  beyond  the  stage  of  vesiculation,  and 
pustules  may  therefore  be  absent.  In  severe  and  protracted  cases, 
however,  a  purulent  fluid  is  secreted  and  the  vesicles  are  converted 
into  pustules.  Deep  ulcerations  may  develop  when  a  large  quantity 
of  pus  is  produced;  in  confluent  cases  the  inflammation  may  be  so 
severe  as  to  lead  to  patches  of  gangrene,  particularly  upon  the  abdomen 
and  legs. 

The  stage  of  vesiculation  or  pustulation  is  followed  by  crusting  of 


THE  VA  R  fO  /.  0  US  T)  THE  A  SES  O  F  L  0  W  EAi  A  NIMA  LS  ]  .'J7 

the  lesions,  constituting  tlic  process  of  dcsiccidion.  'I'lic  scabs  arc  of 
a  l)roiwnisli-ycIlow  or  l)lackisli  color,  and  vary  considerably  in  voluin(;. 
When  tluvse  fall  olf  jyil.s  nvv  seen  in  the  skin,  which  v;iry  in  dej>tli  accord- 
ing to  the  severity  of  the  disease.  Two  to  four  weeks  may  elafxse  before 
the  complete  iiealing  of  the  sores.  At  the  sites  of  the  lesions  {permanent 
defects  remain  in  the  wool  of  the  animal. 

In  confiuent  cases  the  fever  remains  high,  there  is  rapid  respiration, 
moaning,  frothy  discharge  from  the  n)outh,  and  at  times  destructive 
lesions  of  the  eyelids  and  eyeball;  a  severe  diarrhrx-a  may  hasten  the 
fatal  termination.  Jn  such  cases  the  slightest  ap{)lication  of  force  may 
cause  the  wool  to  separate  from  the  skin. 

Captain  J.  Carr  (quoted  l)y  Simonds)  thus  describes  this  malignant 
form:  "The  pulse  becomes  increasingly  rapid,  the  mouth  dry  and  hot, 
the  breath  fetid,  and  the  eyelids  and  even  head  so  much  swollen  that 
the  creature  can  scarcely  be  recognized.  The  pustules  mav  produce 
malignant  ulcers  and  render  the  poor  animal  lame  or  blind." 

Sacco  states  that  "impregnated  ewes  are  certain  to  al)ort  their  lamljs." 

The  mortality  rate  is  high,  varying  between  25  and  50  per  cent.  When 
death  takes  place  it  is  most  apt  to  occur  during  the  first  week  of  the 
eruption. 

That  the  disease  may  be  conveyed  through  the  atmosphere  is  evidenced 
by  the  fact  that  sheep  that  have  never  come  in  contact  with  infected 
anim.als,  but  have  been  kept  in  neighboring  pens,  have  contracted  the 
disease. 

Youatt  states  of  sheeppox  that  "if  it  broke  out  in  a  flock,  it  was  almost 
sure  to  be  communicated,  sooner  or  later,  to  all  that  were  within  a  few 
hundred  yards  of  it." 

The  disease  may  also  be  conveyed  by  inoculation ,  or  ovination,  as  it 
has  been  termed.  Ovination  has  been  extensively  employed  in  order 
to  mitigate  the  ravages  of  natural  sheeppox.  The  disease  under  such 
circumstances  commonly  develops  after  four  to  eight  days,  and  when 
performed  with  special  precautions  usually  produces  a  milder  malady 
than  when  contracted  in  the  usual  manner.  D'Arboval  records  the 
fact  that  of  32,317  sheep  inoculated,  32,121  took  the  disease,  of  which 
31,851  recovered  and  270  died.  The  inoculated  sheep  to  the  number 
of  7697  were  subsequently  exposed  to  the  infection  of  sheeppox  without 
any  of  them  contracting  it.  Inoculation  was  not  so  successful  in  the 
hands  of  Simonds  and  of  Ceely,  who  lost  in  their  first  experiments 
almost  20  per  cent,  of  their  sheep. ^ 

It  has  been  stated  that  ovination  of  pregnant  ewes  will  subsequently 
protect  the  newborn.  This  is  denied  by  D'Arboval,  who  says  that  the 
lambs  born  of  sheep  which  had  been  affected  wdth  the  natural  clavelee 
(sheeppox),  or  those  which  were  inoculated  during  pregnancy,  do  not 
acquire  an  immunity  thereby  from  the  malady. 

Some  difference  of  opinion  exists  as  to  the  prophylactic  power  of 
vaccination  against  variola  ovina.    D'Arboval  contends  that  inoculation 

'  These  experiments  were  conducted  on  a  much  smaller  scale  than  those  of  D'Arboval. 


138  THE  VARIOLOUS  DISEASES  OF  LOWER  ANIMALS 

of  a  large  number  of  sheep  with  virus  from  the  cow  failed  to  protect 
them  against  sheeppox.  Sacco,  on  the  other  hand,  declares  that  "he 
has  fully  satisfied  himself  by  repeated  experiments  of  the  power  of 
vaccination  to  destroy  the  susceptibility  of  sheep  to  contract  variola 
ovina." 

Human  Ovination. — Sacco  inoculated  about  300  children  with  the 
virus  of  sheeppox  and  claimed  that  the  ovination  protected  them  against 
smallpox.  He  states:  "I  subsequently  determined  to  inoculate  two 
children  with  ovine  lymph  on  one  arm  and  vaccine  on  the  other;  the 
vesicles  were  so  similar  in  appearance  that  had  I  not  marked  the  arms 
I  should  not  have  been  able  to  distinguish  the  one  vesicle  from  the 
other.  A  few  days  after  the  desiccation  of  the  vesicles  the  children 
were  inoculated  with  the  virus  of  human  smallpox,  but  no  consequences, 
either  local  or  general,  resulted  therefrom." 

The  successful  inoculation  of  sheep  virus  in  the  human  subject  is, 
however,  much  more  difficult  than  would  appear  from  the  above  state- 
ment, inasmuch  as  Simonds,  Ceely,  and  Marson  all  failed  in  similar 
attempts,  although  the  two  latter  investigators  performed  no  less  than 
250  inoculations.  D'Arboval  also  failed  in  conveying  ovine  lymph 
to  the  human  subject,  for  he  states  that  he  successfully  vaccinated  a 
number  of  children  after  ovination  had  been  tried.  He  also  remarks 
that  efforts  to  communicate  sheeppox  by  inoculation  to  horses,  oxen, 
goats,  deer,  pigs,  dogs,  monkeys,  rabbits,  and  various  birds  were  likewise 
unsuccessful. 

We  believe  the  conclusion  may  be  drawn  that  while  the  smallpox  of 
sheep  and  that  of  man  resemble  each  other  clinically,  and  are  doubtless 
closely  related  to  one  another,  the  two  diseases  are  not  identical.  It 
would  appear  that  sheeppox  may  at  times  be  inoculated  into  the  human 
subject,  but  there  is  no  reason  to  believe  in  the  intercommunicability  of 
human  and  ovine  variola  by  ordinary  infection.  No  one  has  ever 
observed  the  smallpox  of  sheep  give  rise  to  smallpox  in  man,  nor  has 
the  reverse  route  of  infection  ever  been  recorded. 

Goatpox. — The  existence  of  a  primary  goatpox  is  doubted  by  most 
authors,  the  view  being  held  that  this  animal,  which  is  zoologically  closely 
related  to  the  sheep,  contracts  the  disease  from  the  sheeppox.  The 
goatpox  is  accompanied  by  high  fever  and  a  generalized  eruption. 
The  disease  is  extremely  rare. 

That  the  goatpox  is  similar  in  its  nature  to  cowpox  appears  probable 
from  information  contained  in  a  letter  written  by  Prof.  Heydeck  to 
Dr.  Dunning,  and  quoted  by  Baron.  The  letter  reads:  "The  King 
ordered  in  September  that  all  the  children  in  the  Foundling  House 
should  be  inoculated  with  the  goatpock,  which  did  its  effects." 

Variola  Equina,  Horsepox,  Grease  or  Eaux  aux  Jambes.— The 
various  appellations  here  mentioned  have  been  applied  to  a  pock  disease 
in  the  horse  which  bears  a  close  relationship  to  vaccinia  and  variola. 
The  term  grease,  Jenner  tells  us,  was  employed  by  farriers  to  designate 
this  disease  upon  the  heels  of  horses.  It  is  regretted  by  some  writers 
that  Jenner  used  this  term  instead  of  variola  equina,  for  the  employment 


77//';  VMiioLous  i>isI':asi<:s  of  low/'JH,  animals        ]'.>/.) 

of  this  name  has  given  rise  to  some  conriision.  iyii|jtoi)'  in  ISOf)  pointed 
out  that  the  true  analogy  of  eowpox  in  the  liors(;  was  not  tin-  f/rea.fe 
nor  any  form  of  (jrcase,  hut  a  disease  regarded  ijy  the  neighhoring 
farmers  as  widely  different  from  it,  and  caUed  by  them  "serateiiy  heel." 

Loy  in  1801  (listinguish(>(l  two  forms  of  grease,  the  aente  and  the 
ehronie,  the  former  of  whieli  alone  was  capable  of  imparting  the  disease 
to  the  bovine  of  human  sj)eeies. 

llorscpox,  unlike  the  variolous  disease  in  man  and  in  sheep,  d(jes 
not  seem  to  arise  through  the  action  of  a  volatile  contagiurn,  but  practi- 
cally always  results  from  inoculation,  either  accidental  or  intended,  '^rhe 
disease  is  ushered  in  with  fever,  but  this  in  many  cases  is  slight  and 
often  al)sent.  The  eru})tion  exhibits  a  decided  preference  for  the  fetlock 
joints  of  the  hind  legs,  perhaps  because  these  parts  are  most  subjected 
to  traumatisms.  The  eruption  is  in  many  cases  limited  to  this  region, 
but  a  more  general  eruption  may  exist  either  primarily  or  result  second- 
arily from  autoinoculation.  Perhaps  the  not  infrequent  presence  of 
lesions  in  the  nasolabial  region  may  be  explained  upon  the  grounds 
of  autoinoculation.  Occasionally,  more  particularly  in  certain  epizootics, 
an  extensive  eruption  may  be  present,  involving  the  head,  belly,  and 
legs.  Such  profuse  eruptions  may  be  primary  or  may  appear  after 
the  ordinary  local  symptoms  have  manifested  themselves.  The  lesions 
begin  as  firm  papules,  which  soon  become  flattened  and  are  often 
umbilicated.  By  the  eighth  or  ninth  day  there  are  seen  pea-sized,  round, 
notably  elevated  vesicles,  which  on  rupture  give  exit  to  a  viscid,  yellowish 
fluid.  The  surrounding  skin  is  reddened  and  tumefied.  The  pocks 
may  now  be  transformed  into  superficial,  slowly  healing  ulcers,  or  may 
be  covered  with  crusts,  which  fall  off  from  the  fifteenth  to  the  twenty- 
fifth  day. 

Jenner  briefly  refers  to  grease  in  the  following  words:  "The  skin  of 
a  horse  is  subject  to  an  eruptive  disease  of  a  vesicular  character,  which 
vesicle  contains  a  limpid  fluid,  showing  itself  most  commonly  in  the 
heels.  The  legs  first  become  oedematous,  and  then  fissures  are  observed. 
The  skin  contiguous  to  these  fissures,  when  actually  examined,  is  seen 
studded  with  small  vesicles  surrounded  by  an  areola.  These  vesicles 
contain  the  specific  fluid." 

It  will  be  seen  from  the  above  description  that  equine  and  bovine 
variola  closely  resemble  each  other.  The  disease  in  the  horse  distin- 
guishes itself  from  that  in  the  cow  principally  by  the  locality  of  the 
eruption — usually  the  heels  and  the  nasolabial  mucous  membrane,  the 
occasional  tendency  to  generalization  of  the  eruption,  and  by  attacking 
the  male  as  well  as  the  female. 

The  Relation  of  the  Equine  Disease  to  Cowpox.— Great  interest 
attaches  to  this  subject  inasmuch  as  Jenner  regarded  grease  as  the 
progenitor  of  cowpox.  Jenner  informs  us  that  in  dairy  counties  in 
England  it  was  frequently  the  custom  for  farm  hands  to  dress  the  sores 
on  horses  and  subsequently,  without  due  attention  to  cleanliness,  to 

1  Medical  and  Physical  Journal,  November,  ISOO,  vol.  iv. 


140  THE  VARIOLOUS  DISEASES  OF  LOWER  ANIMALS 

milk  the  cows.  In  this  manner  infectious  matter  was  carried  to  the 
teats  of  cows,  producing  the  cowpox.  From  this  source  other  cows  and 
many  of  the  dairy  hands  became  infected. 

Numerous  experiments  have  proven  the  correctness  of  Jenner's 
assertion  that'  cowpox  results  from  inoculation  with  matter  from  the 
grease.  Woodville  took  exception  to  this  view,  basing  his  contentions 
upon  the  negative  experiments  of  the  veterinary  professor,  Coleman ;  the 
latter,  however,  after  many  unsuccessful  results,  succeeded  in  producing 
cowpox  from  the  grease.  The  horsepox  has  been  artificially  produced 
in  the  horse  and  other  animals  by  inoculation.  This  can  be  done  with 
equine  lymph  directly  transferred  from  horse  to  horse,  with  equine 
lymph  that  has  been  successfully  passed  through  the  cow  (in  other  words, 
with  vaccine  virus  of  equine  origin),  and  finally  with  pure  cow  lymph. 
In  horsepox  produced  by  inoculation,  the  eruption,  almost  without 
exception,  is  limited  to  the  site  of  the  introduction  of  the  lymph. 

The  belief  entertained  by  Jenner,  that  the  grease  was  the  invariable 
source  of  natural  cowpox,  is  not  concurred  in  by  most  observers.  There 
are  many  modern  writers  who  are  of  the  opinion  that  horsepox  is  noth- 
ing more  than  a  variola  or  vaccinia  accidentally  derived  from  the  human 
or  bovine  species.  That  the  latter  theory  is  correct  is  rendered  probable 
in  view  of  the  fact  that  both  cowpox  and  human  variola  may  be  trans- 
planted to  the  horse  with  the  production  of  horsepox. 

Chauveau  injected  vaccine  lymph  beneath  the  skin  and  into  the 
bloodvessels  and  lymphatics  of  colts,  and  produced  ageneralized  eruption 
of  horsepox. 

Copeman  remarks  that  in  all  probability  Jenner  was  mistaken  in  his 
assumption  that  "grease,"  in  the  sense  of  horsepox,  was  a  necessary 
antecedent  to  cowpox;  but  at  the  same  time  there  can  be  little  doubt 
that  the  two  diseases  are  very  closely  allied,  if,  indeed,  they  be  not 
identical," 

We  may  assume  that  the  two  diseases  have  a  common  ancestry, 
without  unavailingly  attempting  to  adduce  proof  as  to  the  priority  of 
either.  There  is  equal  reason  to  believe  that  the  hands  of  the  groom 
may  carry  the  infection  from  the  cow  to  the  horse  as  well  as  from  the 
horse  to  the  cow. 

Human  Equination. — Horsepox  has  been  successfully  inoculated  into 
the  human  subject,  with  the  production  of  vesicles  similar  to  those 
observed  in  cowpox,  and  with  the  effect  of  conferring  immunity  against 
smallpox. 

J.  G.  Loy^  succeeded  in  transferring  lymph  from  cases  of  equine 
variola  to  the  teats  of  cows,  producing  in  them  typical  cowpox.  From 
the  vesicles  thus  formed  he  inoculated  children  and  secured  beautiful 
vaccine  lesions.  He  furthermore  inoculated  horsepox  directly  into  the 
human  species.  We  quote  his  description  of  the  results :  "Some  grease 
matter,  obtained  from  the  same  horse,  was  inserted  in  the  arm  of  a 
child.     On  the  third  day  a  small  degree  of  inflammation  surrounded 

1  Experiments  on  the  Origin  of  the  Cowpox,  England,  1801,  pamphlet  of  29  pages. 


Till:   VA/i/(}fJ)IIS  DISICASKH  OF  LOW  Ell   ANIMALS  \\\ 

tlui  wound.  On  (,li(^  roui'lJi  (liiy  tin;  iiiociiljilcd  phicc  was  iniich  elevated, 
and  a  vesicle  oi"  a  purple  color  was  fornied  on  tlie  fil'lli  day;  on  the  sixth 
and  seventh  (hiys  the  vesicle  increased  and  the  inflannruition  ext<;nded 
and  became  of  a  deeper  color;  on  the  san)e  day  a,  chilliness  came  on, 
attended  w^ith  nausea  and  some  vomiting.  'J'hcse  w(;re  soon  succeeded 
by  increased  heat,  pains  in  the  head,  and  a  frerjuency  of  breathirif^; 
the  feverish  symptoms  soon  abated  and  disapj)cared  entirely  on  the 
ninth  day.  On  the  sixth  day  smallpox  virus  was  inserted  into  the  same 
arm  in  which  the  matter  of  grease  had  been  placed,  but  at  a  considerable 
distance  from  it.  On  the  fourth  and  fifth  days  of  the  smallpox  inocu- 
lation some  redness  appeai-ed  al)out  the  wound,  and  on  the  sixth  a 
small  vesicle.  '^Fhe  inflamniation  now  decreased  and  on  llic  tiinlli  day 
the  vesicle  was  converted  into  a  scab." 

From  this  child,  on  the  sixth  day,  before  the  smallpox  firus  was 
inserted,  matter  was  procured  and  inoculated  int(j  five  other  children. 
A  vesicle  was  produced  in  each  case.  Ten  days  after  the  insertion  of 
the  lymph  the  children  were  all  inoculated  with  smallpox  virus,  but 
nothing  developed  save  a  little  inflammation  at  the  site  of  the  punc- 
tures. 

The  Italian  investigator,  Sacco,  in  a  letter  written  to  Jenner  in  ISO'3, 
describes  similar  experiments:  "A  coachman  came  to  the  hospital 
for  an  eruption  which  he  had  on  his  hands.  It  was  immediately  recog- 
nized that  he  had  contracted  horsepox  in  caring  for  and  dressing  horses. 
I  made  nine  inoculations  (from  the  sores)  on  as  many  children.  Three 
of  these  contracted  an  eruption  exactly  like  that  of  vaccinia.  I  made 
other  inoculations  with  the  material  from  these  children,  and  it  has 
already  been  reproduced  in  four  generations,  with  the  same  effect  as  the 
vaccine  disease.  I  inoculated  several  of  these  individuals  with  smallpox, 
but  without  any  effect.  I  also  finally  obtained,  with  the  virus  of  grease 
inoculated  into  six  other  children,  two  lesions  exactly  like  vaccine 
lesions." 

Martin,  of  Boston,  observed  a  case  of  casual  horsepox  in  1881,  and 
obtained  typical  vaccine  vesicles  therefrom.  He  was  "called  to  a  man 
of  about  sixty,  in  bed  with  considerable  headache  and  febrile  reaction. 
He  presented  vesicular  sores,  two  upon  the  right  hand  and  one  upon 
the  nose,  surrounded  by  areolae,  and  very  painful.  These  lesions  had 
existed  for  about  five  or  six  days.  The  patient  was  employed  as  a 
groom  in  a  horse-car  stable  in  which  were  a  large  number  of  horses 
suflfering  from  sore  heels,  and  his  duties  obliged  him  to  constantly 
handle  these  heels.  The  lesions  in  the  groom  closely  resembled  vaccine 
vesicles,  and  the  exuding  lymph  was  therefore  collected  upon  ivory 
points  and  inoculated  into  several  children  and  a  number  of  heifers. 
In  every  case  a  typical  vaccinal  result  was  obtained.  This  '"stock' 
was  continued  through  cows  for  some  time."  It  is  interesting  to  note 
that  Martin  discovered  casual  cowpox  at  Cohasset  during  the  same 
month. 

A  number  of  other  competent  observers  have  confirmed  the  above 
experiments;  so  that  it  may  be  accepted  that  human  beings  can  be 


142  THE  VARIOLOUS  DISEASES  OF  LOWER  ANIMALS 

equinated  with  virus  taken  from  the  horse,  and  that  such  inoculations 
protect  against  smallpox. 

Retro-equination  has  been  successfully  essayed  in  horses  with  bovine 
or  human  virus  of  equine  origin. 

Natural  Vaccinia,  or  Cowpox  in  the  Cow. — Cowpox  of  spontaneous 
development  is  occasionally  discovered  in  members  of  the  bovine  species. 
The  disease  in  such  cases  is  designated  natural  cowpox  in  contradis- 
tinction to  the  affection  inoculated  by  design.  Natural  cowpox  is  an 
uncommon  disease;  indeed,  it  is  so  rare  that  to  each  case  attaches  an 
historical  interest.  From  each  cow  with  spontaneous  cowpox  a  special 
strain  of  lymph  is  cultivated  and  perpetuated,  so  that  these  first  sources 
are  most  highly  prized.  The  disease  is  most  apt  to  be  observed  in  spring 
and  early  summer,  when  cattle  yield  the  most  milk;  while  any  member 
of  the  bovine  family  (even  the  bull)  may  be  attacked,  it  is  particularly 
the  milch  cow  in  which  the  disease  is  found.  The  eruption  is  never 
generalized,  but  is  circumscribed  to  the  udders  or  their  base.  The 
location  of  the  lesions  constitutes  strong  evidence  that  the  hands  of  the 
milker  are  the  most  important  factor  in  the  transmission  of  the  disease. 
When  the  disease  once  appears  in  the  herd,  it  spreads  with  considerable 
rapidity  from  one  cow  to  another. 

The  disease  is  described  by  the  older  writers  as  beginning  with  the 
formation  of  vesicles,  although  these  are  doubtless  preceded  by  a  brief 
stage  of  papulation.  The  vesicles  are  of  a  bluish  color  and  situated 
upon  a  reddened  and  swollen  base.  If  rupture  takes  place  the  vesicle 
is  converted  into  a  superficial  ulcer  with  irregular  edges,  which  may 
heal  with  great  slowness.  Desiccation  begins  about  the  twelfth  day. 
During  the  suppurative  stage  there  is  usually  some  elevation  of  temper- 
ature, loss  of  appetite,  and  a  lessening  of  the  milk  secretion.  Natural 
cowpox  frequently  exhibits  a  succession  of  lesions,  coming  out  in  crops, 
in  this  respect  differing  from  the  inoculated  disease.  After  the  termi- 
nation of  the  disease  depressed  scars  are  left  which  may  often  be  dis- 
tinguished for  years. 

Cowpox,  both  the  natural  and  inoculated  form,  confers  a  permanent 
immunity  against  a  second  attack.  No  authentic  case  has  been  reported 
in  which  a  cow  has  twice  suffered  from  the  disease. 

Casual  or  Accidental  Cowpox  in  Man. — It  was  from  observation  of 
cases  of  casual  cowpox  in  dairy  attendants  that  Jenner  first  conceived 
the  theory  of  vaccination.  These  infections  result  from  the  contact  of 
fluid  from  the  lesions  on  the  cow's  teats  with  abrasions  upon  the  hands 
of  the  milkers;  one,  two,  or  more  lesions  are  produced,  according  to  the 
number  of  excoriations  present.  Upon  areas  of  reddened  skin  there 
soon  spring  up  vesicles  or  blebs,  which  are  of  a  bluish  color,  rounded, 
flat,  and  depressed  in  the  centre.  These  contain  a  lymph  fluid  which 
later  becomes  purulent.  The  surrounding  skin  becomes  reddened  and 
tumefied,  owing  to  the  development  of  an  erysipelatoid  areola  about 
each  lesion.  The  neighboring  lymphatic  glands  become  swollen  and 
painful,  and  the  patient  becomes  feverish.  In  severe  cases  the  illness 
may  be  sufficiently  pronounced  to  enforce  confinement  to  bed  for  a  few 


77//';   VA/UOLOirS  DlSh'ASh'S  OF  IJ)\V/'JI{,  y\NIMALS  |.J;> 

(lays.  In  a  f(!W  days,  however,  ilien;  is  an  ahalcnieiil,  of  llie  loe;il  infhiin- 
inatory  distiirhanee,  and  of  tlie  eonsliint.ional  syniplonis,  and  (lie  |>iJS- 
tules  cither  become  encrusted  or  form  ulcers  which  j^radually  heal  \)y 
granulation.  In  casual  cowpox  the  local  and  constitutional  symptoms 
are  more  severe  than  when  the  disease  is  intentionally  inoculated, 
probably  because  in  the  latter  case  special  precaulions  are  observed. 

Apepox. — ^^rhe  monkey  aj)])ears  to  be  susceptible  both  to  smallpox 
and  vaccinia.  Zuelzer  claims  that  he  produced  true  variola  in  monkeys 
by  inoculation  with  the  blood  and  crusts  of  human  variola.  Cope- 
man  has  also  succeeded  in  inoculating  monkeys  with  the  fluid  from 
lesions  of  human  smallpox.  More  recently  successful  inoculations 
have  been  carried  out  by  Magrath  and  Brinckerhoff."^  Usually  the 
resulting  eruption  is  limited  to  the  sites  of  inoculation,  but  occasionally 
a  generalized  outbreak  occurs  which  may  cover  the  entire  surface  of 
the  body.  Inoculated  smallpox  in  the  monkey  is,  however,  seldom 
fatal.  The  monkey  may  be  rendered  insusceptible  to  smallpox  by 
previous  vaccination. 

It  is  claimed  that  in  the  tropics  apes  sometimes  die  in  large  numbers 
of  natural  smallpox. 

Anderson,  of  Glasgow,  states  that  while  smallpox  was  raging  with 
great  violence  at  St.  Jago,  on  the  west  coast  of  New  Grenada,  monkeys 
were  attacked  with  the  disease  in  the  forests  near  David,  sixty  or  seventy 
miles  away.  Dying  and  dead  monkeys  were  seen  on  the  ground  covered 
with  perfect  pustules  of  smallpox,  and  several  ill  monkeys  w'ere  seen 
on  the  trees,  moving  about  in  a  sickly  manner.  In  the  course  of  a  fort- 
night one-half  of  the  inhabitants  of  the  town  of  David  were  stricken 
with  smallpox.^ 

Smallpox  in  the  Camel. — In  the  province  of  Lus,  in  Beloochistan, 
the  camels  are  said  to  be  subject  to  a  disease  called  "Photoshootur," 
or  the  smallpox  of  camels.  This  disease  is  said  to  be  communicable 
to  the  camel  milkers,  and  is  alleged  to  protect  them  against  smallpox.^ 

.'  Journal  of  Medical  Resonrcli,  February,  1904. 

2  Quoted  by  William  Aitlceu,  Practice  of  Medicine,  ISGS,  p.  258. 

^  Quoted  by  Son  ton,  Indian  Journal  of  Medical  Sciences,  October,  1839. 


CHAPTER    IV. 

SMALLPOX. 

Synonyms. — Latin,  Variola;  French,  La  Petite  Verole;  German, 
Blattern,  or  Pocken;  Italian,  Vajuola. 

Definition. — Smallpox  is  an  acute  infectious  disease  characterized  by 
an  initial  fever  of  about  three  days'  duration,  succeeded  by  an  eruption 
passing  through  the  stages  of  papule,  vesicle,  and  pustule,  ending  in 
incrustation  and  leaving  pits  or  scars,  the  fever  either  intermitting  or 
remitting  in  the  papular  stage  and  increasing  in  the  pustular  stage. 

Derivation  of  Name. — Some  difference  of  opinion  exists  as  to  the 
derivation  of  the  term  variola.  It  is  alleged  by  some  that  it  was  coined 
by  the  monks  during  the  Middle  Ages,  and  that  it  is  the  diminutive  form 
of  the  Latin  word  Varus  (a  papule,  pimple,  or  tubercle),  a  word  found 
in  Pliny.  Other  writers,  however,  believe  it  to  be  derived  from  the 
word  varius,  which  means  spotted  or  variegated. 

The  Saxon  equivalent  pocca,  meaning  a  bag  or  pouch,  has  given  rise 
to  the  English  pock  and  the  German  Pocken.  Syphilis  appeared  in  Europe 
about  1498  and  caused  some  confusion  of  nomenclature,  so  that  it 
became  necessary  to  prefix  the  adjective  small  to  the  term  pock,  or  pox, 
in  order  to  distinguish  it  from  the  great  pox,  or  syphilis.  The  same 
change  was  made  in  French  phraseology;  so  that  at  the  present  day, 
variola  is  designated  smallpox,  or  la  petite  verole,  and  syphilis  the  pox, 
or  la  verole. 

History. — It  is  claimed  by  some  writers  that  the  antiquity  of  smallpox 
dates  back  to  the  time  of  the  Tsche-u  dynasty  in  China,  at  a  period  not 
less  remote  than  a  thousand  years  before  the  Christian  era.  It  is  stated 
that  temples  were  erected  in  honor  of  the  disease,  and  the  goddess  of 
smallpox  was  thus  glorified.  Inoculation,  or  "sowing  the  smallpox," 
it  would  appear  was  practised  in  China  at  a  very  early  period,  the  result 
being  crudely  attained  by  thrusting  crusts  into  the  nostrils. 

Tradition  has  it  also  that  smallpox  existed  among  the  Brahmin  caste 
of  India  from  time  immemorial.  Descriptions  in  some  of  the  ancient 
sacred  writings  of  spotted  and  pustular  skin  diseases  are  alleged  to 
relate  to  smallpox.  Like  the  Chinese,  the  inhabitants  of  Hindoostan 
are  also  said  to  have  worshipped  at  smallpox  shrines  and  to  have  offered 
sacrifices  to  the  presiding  goddess  to  grant  them  protection. 

That  the  Greek  physicians  were  acquainted  with  smallpox  is  open 
to  most  serious  doubt.  Some  authors  have  labored  diligently  to  prove 
that  the  great  vesicular  and  pustular  eruptions  and  ''anthrakes"  which 
Hippocrates  (460-377  B.C.)  speaks  of  relate  to  smallpox.  While  the 
descriptions  are  somewhat  suggestive  of  this  disease,  they  are  far  from 
constituting  satisfactory  evidence. 


SMyiLLPOX  IJo 

The  first  writings  of  tlu;  Roman  period  ])c,Sirin^  upon  I  he  siilijccl.  ;irf; 
those  of  the  Jewish  y)liilo,sof)her  of  Alexanfh'ia,  IMiilo,  wlio  lived  in  the 
first  c(Mitnry.  II !s  (l('S('ri|)tion  of  the  Egyptian  phij^ue'  might  witli 
greater  reason  he  a,ssnm(>(l  to  refer  to  smallf)ox  than  the  writings  of 
Ilippoerates:  "From  the  great  suffering,  natural  to  the  fermentation  of 
festers  so  extensive,  their  bodies  were  tortured  and  their  minds  fiJIerl 
with  horror.  The  lesions  tin-own  out  soon  merged  into  extensive  })listers 
filled  with  pus,  as  if  the  ])arts  had  been  burned.  It  extended  over  the 
whole  body  from  head  to  foot."  This  deseription  is,  as  Ilaeser  contends, 
strongly  suggestive  of  confluent  smallpox. 

Haeser^  concludes,  from  a  study  of  the  Greek  and  Roman  writings, 
"that  knowledge  of  smallpox  among  the  ancient  Greeks  and  Romans 
probably  existed,  although  we  cannot  with  absolute  certainty  either 
affirm  or  deny  this  assertion." 

The  word  "  variola"  is  first  mentioned  by  Bishop  Marius,of  Ivausanne, 
who  employed  the  term  (et  variola  Italiam  Galliamque  afflixit)  in  570  a.d. 
in  describing  a  devastating  epidemic  that  swept  through  Italy  and 
France.  The  same  epidemic  was  doubtless  referred  to  by  Bishop 
Gregory,  of  Tours,  who,  in  582,  under  the  name  of  "lues  cum  vesicis," 
described  a  disease  characterized  at  the  beginning  by  high  fever,  vomit- 
ing, and  "back  pains,"  followed  by  the  appearance  of  a  painful  eruption 
of  hard,  white  vesicles,  which  occurred  most  conspicuously  over  the 
face,  hands,  and  feet;  the  vesicles  became  pustules,  and  in  many  cases 
death  occurred  on  the  twelfth  or  fourteenth  day. 

Procopius,  in  a  chapter  "De  Bello  Persico"  (hb.  ii.,  cap.  27),  described 
a  dreadful  pestilence  which  began  in  Pelusium,  Egypt,  in  the  year  544. 
It  was  accompanied  by  buboes  and  carbuncles  (suggesting  bubonic 
plague),  but  was  widespread,  raged  independent  of  season,  spared 
neither  age  nor  sex,  attacked  pregnant  women  severely,  and  was  a  new- 
disease  but  little  understood  by  physicians. 

A  short  time  afterward,  unequivocal  traces  of  smallpox  are  met  with 
in  countries  bordering  on  the  Red  Sea;  for  we  read  of  caliphs  and 
caliphs'  daughters  being  pitted  and  having  white  spots  in  their  eyes. 

In  569  A.D.  smallpox  appears  to  have  broken  out  in  virulent  form  in 
the  Abyssinian  army  of  Abraha,  which  was  besieging  Mecca.  The 
soldiers  were  decimated  by  the  pestilence,  necessitating  the  raising  of 
the  siege. 

Reference  to  a  lost  treatise  on  smallpox  (seventh  century)  by  an 
Alexandrian  physician,   Aaron,  is  found  in  the  w^ritings  of  Rhazes. 

Edwardes'^  says:  "The  first  clear  description  of  smallpox  by  a 
physician,  which  has  come  down  to  us,  is  by  Isaac,  the  Jew%  who  lived 
in  the  ninth  century.  A  manusci'ipt  latin  translation  of  his  work  is  in 
the  town  library  of  Mainz  (Isaaci  Israeliti.     .     .     .     opera  omnia)." 

The  most  scientific  and  comprehensive  description  of  smallpox  handed 
down  from  these  times,  however,  is  from  the  pen  of  Rhazes,  who  wrote 

1  Vita  Moses,  I,  C.  22,  Ed.  Tauchnitz  (Bonn,  1S38),  tome  iii.  p.  151. 
-  Geschiclite  der  Epidemisehen  Krankheiten,  Jena,  1S65,  p.  27. 
3  Smallpox  and  Vaccination  in  Europe,  1902. 
10 


146  SMALLPOX 

in  about  910.  The  Bagdad  physician  was  a  prohfic  writer  and  a  close 
observer,  and  has  been  called  "the  Arabian  Galen."  The  following 
quotations  are  of  interest: 

"As  soon  as  the  symptoms  of  smallpox  appear  we  must  take  especial 
care  of  the  eyes,  and  then  of  the  throat,  and  afterward  of  the  nose, 

ears,  and  joints If  a  severe  pain  arises  in  the  soles  of  the 

feet,  then  take  care  to  anoint  them  with  tepid  oil,  and  foment  them 
with  hot  water  and  cotton,  ....  for  these  and  the  like  things 
soften  and  relax  the  skin,  and  thus  facilitate  the  eruption  of  the  pustules 
and  lessen  the  pain." 

"All  those  pustules  that  are  very  large  should  be  pricked,  and  the 
fluid  that  drops  from  them  be  soaked  up  with  a  soft,  clean  rag  in  which 
there  is  nothing  that  may  hurt  or  excoriate  the  skin." 

"When  the  desiccation  of  the  pustules  is  effected,  and  scabs  and  dry 
eschars  still  remain  upon  the  body,  examine  them  well,  and  upon  those 
that  are  thin  and  perfectly  dry,  and  under  which  there  is  no  moisture, 
drop  warm  oil  of  sesamum  every  now  and  then,  until  they  are  softened 
and  fall  off." 

.  and  in  order  to  efface  the  pock  holes,  and  render  them 
even  with  the  surface  of  the  body,  let  the  patient  endeavor  to  grow  fat 
and  fleshy,  and  use  the  bath  frequently  and  have  the  body  well  rubbed." 

The  above  therapeutic  suggestions  might  be  incorporated  in  a  modern 
treatise  on  smallpox  with  but  little  revision.  Rhazes  credits  Galen  with 
a  knowledge  of  the  disease,  and  also  quotes  from  Hippocrates,  Aaron, 
and  Masawaih.  The  last-named  writer  is  cited  as  saying :  ".  .  .  Your 
first  care  should  be  directed  to  the  eye,  for  which  you  should  use  a 
coUyrium  made  of  sumach  and  rose-water,  in  order  to  prevent  any 
pustules  from  coming  out  in  it." 

Avicenna  (980-1037),  an  Arabian  physician,  was  the  first  to  dis- 
tinguish smallpox  from  measles.  In  the  Canon  Medicince  he  states 
of  measles  "that  in  it  more  tears  flow."  He  also  conceded  the  possibility 
of  second  attacks  of  smallpox. 

Franciscus  de  Pedemontium  (1330)  referred  to  red  coverings  and 
warm  air  as  tending  to  expel  the  pustules  to  the  surface,  for,  "according 
to  Avicenna  the  sight  of  red  bodies  moves  the  blood." 

Constantinus  Africanus  (1075  a.d.),  a  Carthaginian,  who  lectured  at 
Salerno,  the  first  European  medical  school,  closely  followed,  as  did  his 
contemporaries,  the  Arabian  doctrines.  He  restricted  the  term  variola, 
which  was  at  that  time  loosely  employed,  to  smaflpox. 

A  tenth  century  Anglo-Saxon  manuscript,  in  the  Harleian  collection  in 
the  British  Museum,  contains  an  exorcism  and  prayer  in  which  the  follow- 
ing words  appear:  ".  .  .  ,  Geskyldath  me  vid  de  lathan  Poccas, " 
which,  rendered  into  modern  English,  reads:  "Shield  me  against  the 
hideous  pocks." 

A  Cottonian  manuscript,  evidently  written  in  the  eleventh  century, 
contains  a  prayer  to  Saint  Nicaise,  who  had  the  smallpox,  and  whose 
name  was  to  be  worn  in  an  amulet  to  grant  protection. 

The  term  pocca,  which  was  the  Anglo-Saxon  equivalent  of  variola, 


SMALfJ'OX  147 

is  first  encountered  in  a  tenth-century  leech-book  of  f  he  physician  Bald. 
The  death  of  Baldwin  (1)01),  son  of  the  Earl  of  Flanders,  from  "variolas 
Sive  poccas"  is  set  forth  in  tlu;  Jiniitiidii  (Hirdniclc. 

Smallpox  is  sup|)osed  to  have  invaded  England  between  the  tenth  and 
thirteenth  centuries,  llolinshed,  describing  an  e[;ideniic  in  the  reign 
of  Edward  III.,  writes:  "Also  many  died  of  small  jjoklce.s,  both  men, 
women,  and  children."  According  to  Ilirsch,  Iceland  suflVnerl  frcHn 
smallpox  in  L30f),  having  received  the  infection  from  Denmark. 

John  of  Gaddesden,  physician  of  Edward  II.  and  author  of  Ro.ia 
Anglica,  followed  the  Arabian  treatment  of  surrounding  the  patif-nt 
with  red  bed-clothing,  hangings,  etc.  He  acquired  a  great  reputation, 
but,  according  to  Watson,  was  a  "very  sad  knave." 

During  the  epidemic  of  1694,  Queen  Mary,  the  wife  of  William  III., 
died  at  the  age  of  thirty-three  of  hemorrhagic  smallpox.  I>ord  Macaulay, 
writing  of  the  ravages  of  this  disease,  says: 

"That  disease,  over  which  science  has  achieved  a  succession  of 
glorious  and  beneficent  victories,  was  then  the  most  terrible  of  all 
ministers  of  death.  The  havoc  of  the  plague  had  been  far  more  rapid ; 
but  the  plague  had  visited  our  shores  only  once  or  twice  within  living 
memory;  and  the  smallpox  was  always  present,  filling  the  church-yards 
with  corpses,  tormenting  with  constant  fears  all  whom  it  had  not  yet 
stricken,  leaving  on  those  whose  lives  it  spared  the  hideous  traces  of 
its  power,  turning  the  babe  into  a  changeling  at  which  the  mother 
shuddered,  and  making  the  eyes  and  cheeks  of  a  betrothed  maiden 
objects  of  horror  to  the  lover." 

Smallpox  was  treated  in  diverse  and  various  manners  in  different 
periods.  In  1640  the  hot  or  sweating  treatment,  by  which  the  peccant 
humors  were  to  be  expelled,  was  in  vogue.  Diemerbroeck,  a  Dutch 
physician  and  professor,  was  an  advocate  of  this  method.  Gregory 
remarks  that  when  Sydenham  began  his  medical  reform,  in  1667,  "he 
had  an  Augean  stable  to  cleanse."  The  "Enghsh  Hippocrates,"  how- 
ever, was  equal  to  the  task,  and  succeeded  in  completely  changing  the 
practice  with  regard  to  smallpox.  He  insisted  upon  fresh  air,  and  sub- 
stituted the  cooling  for  the  sweating  treatment.  He  also  described  the 
disease  admirably,  and  was  the  first  to  trenchantly  distinguish  between 
measles  and  smallpox.  Boerbaave  (1668-1738)  was  a  warm  admirer  of 
Sydenham.  He  deserves  the  credit  of  having  maintained  that  smallpox 
was  contagious  and  due  to  a  specific  miasm. 

Smallpox  in  America. — It  is  said  that  smallpox  reached  Mexico  in 
1518,  having  been  brought  by  a  negro  slave  who  accompanied  the 
troops  of  Cortez  from  Cuba.  According  to  Toribio  it  swept  the  country, 
destroying  the  lives  of  three  and  a  half  millions  of  people.  De  la  Con- 
damine  states  that  whole  tribes  of  Indians  were  exterminated,  and  in 
some  places  no  one  was  left  to  bury  the  dead.  The  disease  then  reap- 
peared at  regular  intervals  of  seventeen  or  eighteen  years.  In  1633  the 
Indians  of  Massachusetts  were  attacked  by  smallpox  and  slain  by  the 
thousands.    The  disease  first  appeared  in  Boston  in  1649. 

Referring  to   the  importation   of  smallpox  into   America,  Gregory 


148  SMALLPOX 

humorously  remarks:  "If  America  gave  us,  as  people  confidently  say  it 
did,  the  great  pox,  we  have  more  than  returned  the  compliment  by 
introducing  to  her  acquaintance  the  smallpox." 

In  1707  smallpox  reached  Iceland,  destroying  the  lives  of  16,000 
people,  almost  one-third  of  the  population  of  the  island. 

Period  of  Inoculation. — Inoculation  was  first  practised  in  Constan- 
tinople about  the  year  1674.  Dr.  Timoni  (1714),  Dr.  Kennedy  (1715), 
and  Dr.  Pylarini  (1716)  wrote  on  the  subject  of  inoculation,  but  the  pro- 
fession in  England  ignored  the  publications.  It  remained  for  the 
charming  and  accomplished  Lady  Mary  Wortley  Montague,  wife  of  the 
British  Ambassador  to  Turkey,  to  introduce  inoculation  to  the  Euro- 
pean world.  The  now  famous  letter  to  her  friend.  Miss  Sarah  Chis- 
well,  written  in  1717,  is  here  appended: 

".  .  .  Apropos  of  distempers,  I  am  going  to  tell  you  a  thing  that  will  make  you  wish  yourself 
here.  The  smallpox,  so  fatal  and  so  general  amongst  us,  is  here  entirely  harmless  by  the  invention 
of  engrafting,  which  is  the  term  they  give  it.  There  is  a  set  of  old  women  who  make  it  their  business 
to  perform  the  operation,  every  autumn  in  the  month  of  September,  when  the  great  heat  is  abated. 
People  send  to  each  other  to  know  if  any  of  their  family  has  a  mind  to  have  the  smallpox :  they 
make  parties  for  this  purpose,  and  when  they  are  met  (commonly  fifteen  or  sixteen  together)  the  old 
woman  comes  in  with  a  nutshell  of  the  best  sort  of  smallpox,  and  asks  what  vein  you  please  to  have 
opened.  She  immediately  rips  open  that  you  offer  to  her  with  a  large  needle  (which  gives  no  more 
pain  than  a  common  scratch),  and  puts  into  the  vein  as  much  matter  as  can  lie  upon  the  head  of 
her  needle,  and  after  that  binds  up  the  little  wound  with  a  hollow  bit  of  shell,  and  in  this  manner 
opens  four  or  five  veins.  .  .  .  The  children  or  young  patients  play  together  all  the  rest  of  the 
day  and  are  in  perfect  health  to  the  eighth.  Then  the  fever  begins  to  seize  them,  and  they  keep 
their  beds  two  days,  very  seldom  three.  They  have  very  rarely  above  twenty  or  thirty  on  their  faces 
(sic),  which  never  mark,  and  in  eight  days'  time  they  are  as  well  as  before  their  illness.  Where  they 
are  wounded  there  remain  running  sores  during  the  distemper,  which  I  do  not  doubt  is  a  great  relief 
to  it.  Every  year  thousands  undergo  this  operation,  and  the  French  Ambassador  says,  pleasantly, 
that  they  take  the  smallpox  here  by  way  of  diversion,  as  they  take  the  waters  in  other  countries. 
There  is  no  example  of  anyone  that  has  died  of  it,  and  you  may  believe  that  I  am  well  satisfied  of 
the  safety  of  this  experiment,  since  I  intend  to  try  it  on  my  dear  little  son.  I  am  patriot  enough 
to  take  pains  to  bring  this  useful  invention  into  fashion  in  England,  and  I  should  not  fail  to  write 
to  some  of  our  doctors  very  particularly  about  it,  if  I  knew  any  one  of  them  that  I  thought  had  virtue 
enough  to  destroy  such  a  considerable  branch  of  their  revenue  for  the  good  of  mankind.  But  that 
distemper  is  too  beneficial  to  them,  not  to  expose  to  all  their  resentment  the  hardy  wight  that 
should  undertake  to  put  an  end  to  it.  Perhaps  if  I  live  to  return,  I  may,  however,  have  courage  to 
war  upon  them.    Upon  this  occasion  admire  the  heroism  in  the  heart  of 

"Your  friend,"  etc. 

The  daughter  of  Lady  Montague  was  the  first  person  ever  inoculated 
in  England  (1727),  although  her  son  had  previously  been  inoculated  in 
Constantinople.  In  the  following  year,  after  six  condemned  criminals  had 
been  successfully  inoculated,  the  two  daughters  of  the  Princess  of 
Wales  submitted  to  the  new  process. 

During  the  first  ten  years  of  its  career  inoculation  met  with  great 
opposition.  Later  it  became  more  firmly  established,  and  was  exten- 
sively practised  in  England  up  to  1800.  It  never,  however,  became 
popular  on  the  Continent.  The  average  death  rate  from  inoculation 
was  about  one  in  three  hundred  cases,  although  it  often  rose  above  this. 
In  1798  Jenner  announced  his  discovery  of  vaccination.  In  1808  the 
inoculation  of  out-door  patients  was  discontinued  at  the  London  Small- 
pox Hospital,  and  fourteen  years  later  inoculation  of  in-door  patients 
was  abandoned.  In  1843  Gregory  wrote:  "In  1840  the  practice  of 
inoculation,  the  introduction  of  which  has  conferred  immortality  on 


smaIjIjPox  140 

the  name  of  Lady  Montague,  which  had  been  sanctiouc*!  hy  the  College 
of  Physicians,  which  had  saved  the  lives  of  many  kings,  (queens,  and 
princes,  and  of  thousands  of  their  subjects  during  the  greater  part  of 
the  preceding  century,  was  declared  illegal  by  the  Knglish  J'arliarnent, 
and  all  offenders  were  sent  to  j)rison  with  a  gf)od  flianre  of  the  tread- 
mill. .  .  .  Such  are  the  reverses  of  fortune  tf)  vvhicli  all  siibhjriyry 
things  are  doomed." 

Inoculation  was  first  practised  in  America  in  1721 .  It  was  introduced 
into  this  country,  at  the  suggestion  of  the  Rev.  Cotton  Mather,  by  Dr. 
Zabdiel  Boylston,  of  Boston,  who  first  inoculatecl  his  only  son  anrl  then 
two  negro  servants.  Before  the  practice  was  generally  aecept(;d,  how- 
ever, it  was  necessary  to  overcome  here,  as  in  England,  niueli  \io!ent 
opposition. 

The  principal  advantage  claimed  for  inoculation  was  that  smallpox 
thus  produced  was  much  milder  in  type  than  when  the  infection  was 
received  in  the  natural  way;  while  the  death  rate  from  smallpox  was 
one  out  of  every  three  or  four  persons  attacked,  it  was,  at  the  highest 
from  tlie  inoculated  disease,  not  greater  than  one  out  of  fifty,  and  some- 
times as  low  as  one  out  of  three  hundred,  the  average  death  rate  being 
somewhere  between  the  two.  Not  only  the  number  of  deaths,  but  the 
marred  visages  of  persons  in  every  community,  testified  to  the  frequency 
of  smallpox  before  the  days  of  inoculation.  Indeed,  it  was  so  preva- 
lent in  the  Middle  Ages  as  to  lead  to  the  common  saying  that  "from 
smallpox  and  love  but  few  remain  free."  The  disadvantage  of  inocu- 
lation was  that  smallpox  produced  in  this  manner,  although  milder  in 
type,  was  just  as  contagious  as  when  contracted  naturally;  hence  inocu- 
lation had  the  effect  of  keeping  the  disease  almost  constantly  in  existence. 

Prevalence  of  Smallpox  in  the  Prevaccination  Days. — Smallpox  was  so 
universal  a  disease  that  Ben  Jonson  wrote  of  it: 

"Envious  and  foul  disease,  could  there  not  be 
One  beauty  in  an  age  and  free  from  thee?" 

Smallpox  was  mainly  a  disease  of  children  in  former  times,  and 
the  adult  population  consisted  for  the  most  part  of  the  survivors  from 
an  attack  in  childhood,  therefore  permanently  pi'otected.  The  disease 
was  regarded  as  universal  or  almost  universal. 

According  to  Dr.  Lettsom,  most  children  in  London  had  smallpox 
before  the  seventh  year. 

Juncker  estimated  that  400,000  smallpox  deaths  occurred  yearly  in 
Europe  on  an  average,  and  that  five-sixths  of  mankind  were  attacked. 
Many  writers  were  of  the  opinion  that  every  one  was  attacked  sooner  or 
later.  King  Frederick  William  III.  of  Prussia,  in  a  dispatch  dated 
October  31,  1803,  states  that  smallpox  caused  on  an  average  40,000 
deaths  yearly  in  Prussia.^ 

That  smallpox  did  not  respect  royalty  is  evidenced  by  the  formidable 
list  of  kings,  queens,  and  princes  who  died  of  the  disease:  William  II 
of  Orange,  Emperor  Joseph  I.  of  Austria,  Louis  XV.  of  France,  two 

1  The  above  statements  are  quoted  from  Edwardes'  Smallpox  and  Vaccination  in  Europe,  1902. 


150  SMALLPOX 

children  of  Charles  I.  of  England,  a  son  of  James  II.  of  England,  his 
daughter  Queen  Mary,  and  her  uncle,  the  Duke  of  Gloucester;  the  son 
of  Louis  XIV.;  Louis,  Duke  of  Burgundy;  the  dauphin,  his  wife,  and 
their  son,  the  Due  de  Bretagne;  Peter  11. ,  Emperor  of  Russia;  Henry, 
Prince  of  Prussia;  the  last  Elector  of  Bavaria,  two  German  empresses, 
six  Austrian  archdukes  and  archduchesses,  an  Elector  of  Saxony, 
and  the  Queen  of  Sweden  (174L)  The  following  were  attacked  with 
the  disease,  but  recovered:  Queen  Anne  of  England,  Peter  HI.  of 
Russia,  Louis  XIV.  of  France,  William  of  Orange  (afterward  Will- 
iam III.),  and  Queen  Maria  Theresa  of  Austria.  George  Washington 
was  "strongly  attacked  by  the  smallpox"  during  his  early  manhood, 
while  on  a  visit  to  the  West  Indies. 

THE  ETIOLOGY  OF  SMALLPOX. 

That  smallpox  may  prevail  in  the  frigid  climes  of  Greenland  and  in 
the  torrid  regions  of  Africa  is  evidence  of  the  fact  that  conditions  of  soil 
or  climate  exert  but  little  influence  over  the  disease.  Practically  no 
civilized  country  on  the  globe  has  been  exempt  from  the  ravages  of 
smallpox.  It  follows,  like  other  transmissible  diseases,  the  channels 
of  trade  and  human  intercourse.  W^hen  the  contagium  of  the  disease 
is  brought  to  an  unprotected  community,  there  the  malady  takes  root 
and  spreads. 

Susceptibility  to  smallpox  is  almost  universal;  but  few  persons  can 
boast  of  natural  immunity  from  this  disease.  Yet  this  individual  pecu- 
liarity is  occasionally  encountered,  as  may  be  seen  by  reference  to  the  his- 
tory of  the  disease  during  the  prevaccination  period.  Persons  have  been 
known  to  go  through  life  constantly  exposed  to  the  infection  without 
suffering  from  any  manifestation  of  smallpox.  It  is  said  that  Morgagni, 
Boerhaave,  and  Diemerbroeck  enjoyed  this  privilege.  It  is  not  impos- 
sible that  such  immunity  may  have  resulted  from  a  mild  attack  of 
smallpox,  from  which  such  persons  may  have  suffered  in  utero,  even 
without  their  mothers  having  presented  any  manifestations  of  the 
disease. 

Instances  are  recorded  in  which  persons  have  resisted  the  infection 
when  exposed  in  the  usual  manner,  but  have  yielded  to  the  disease  by 
inoculation  later  in  life.  Gregory  gives  an  example  of  this  kind  in  the 
case  of  a  lady  who  brought  up  a  large  family  of  children,  many  of 
whom  she  nursed  through  smallpox  without  receiving  the  infection 
herself,  but  at  the  age  of  eighty-three  she  took  the  disease  by  inoculation. 
While  but  few  are  naturally  insusceptible  to  smallpox,  through  the 
agency  of  vaccination,  individual  susceptibility  at  the  present  day,  is 
greatly  changed;  absolute  immunity,  indeed,  is  enjoyed  by  the  greater 
part  of  the  population. 

Instances  are  met  with,  under  rare  circumstances,  of  apparently 
healthy  persons  resisting  the  infection  of  smallpox  at  one  time  and 
yielding  to  it  at  another.  We  will  relate  a  case  in  point:  In  1874  a 
colored  man  of  thirty  years  came  under  our  care  suffering  from  con- 


THE  ETIOLOd  Y  Oh'  SMA  LLI'OX  151 

fluent  variola.  He  stated  that  vaccination  had  \ntvA)  \n-YU)vu\i-A  at 
difi:'erent  times  during  his  life,  but  never  successfully:  In  1871  he 
belonged  to  the  crew  of  a  sailing  vessel  in  v^^hich  several  cases  of  smallpox 
occurred,  and  his  duties  required  him  to  fre(|ii('ntly  come  in  ffjiitact 
with  those  who  were  ill,  yet  he  did  not  take  the  disease.  He  was  vao 
cinated  at  that  time,  but,  as  before,  without  result.  When  he  fell  ill  with 
variola  three  years  later  he  was  unable  to  account  f(;r  the  source  of  the 
infection.    The  attack  proved  fatal. 

In  the  days  when  inoculation  was  extensively  practised  it  was  noticed 
that  some  persons  exhibited  a  temporary  insusceptibility  to  the  infec- 
tion. Gregory  informs  us  that  Woodville  found  one  out  of  every  sixty 
children,  and  one  out  of  twenty  adults,  to  be  temporarily  insusceptible 
to  inoculation.  Experience  demonstrates  that  the  susceptibility  to 
smallpox  may  at  one  time  be  diminished  and  at  another  greatly  increased. 

The  existence  of  acute  and  chronic  infectious  diseases  is  said  by  some 
writers  to  temporarily  lessen  the  susceptibility  to  the  infection  of  variola. 
Curschmann  asserts  "  that  for  an  individual  suffering  from  scarlet  fever, 
measles,  or  typhoid  fever,  there  is  during  the  entire  duration  of  the 
affection  only  a  very  slight  susceptibility  to  an  attack  of  variola."  He 
observed  in  the  hospital  at  Mayence  (where  the  smallpox  building  was 
near  the  general  wards)  that  variolous  infections  never  took  place  during 
the  course  of  the  typhoid  process.  A  considerable  number  of  typhoid 
convalescents,  however,  were  attacked  after  their  temperatures  had 
become  permanently  normal.  He  was  led  to  this  conclusion  from  the 
fact  that  the  interval  between  the  time  of  the  subsidence  of  the  fever 
and  the  beginning  of  the  initial  stage  of  variola  corresponded  to  the 
longest  period  of  incubation  that  is  encountered — namely,  fourteen  to 
nineteen  days.  There  is  no  doubt,  however,  that  the  variolous  infection 
does  frequently  occur  during  the  existence  of  an  acute  disease,  only 
the  incubation  period  in  such  cases  is  often  greatly  prolonged.  Smallpox 
has  been  known  to  exist  with  the  acute  exanthemata,  particularly  scarlet 
fever  and  measles.  We  have  seen  unprotected  children,  while  suffering 
from  measles  in  its  most  acute  stage,  exposed  not  longer  than  two 
minutes  to  the  infection  of  variola,  sicken  with  the  disease  after  the 
usual  incubation  period.  We  have  also  observed  this  sequence  of  events 
to  develop  in  connection  with  a  diphtheria  patient.  In  at  least  a  half- 
dozen  instances  we  have  noted  the  coexistence  of  smallpox  and  scarlet 
fever.  Chronic  infectious  maladies,  such  as  syphilis  and  tuberculosis, 
not  infrequently  exist  in  individuals  who  are  attacked  by  smallpox. 

Recurrent  Smallpox  (Second  Attacks). — The  susceptibility  to  small- 
pox is  removed  by  vaccination,  but  frequently  reappears  to  a  greater  or 
less  degree  in  a  variable  period  of  time.  So  also  one  attack  of  smallpox 
does  not  invariably  protect  the  individual  for  the  remainder  of  his  life 
against  a  future  attack.  It  is  undoubtedly  the  rule  that  a  person  does 
not  suffer  from  the  disease  more  than  once,  but  well-authenticated 
cases  of  second  attacks  are  recorded.  Indeed,  some  writers  allege  that 
the  predisposition  to  smallpox  in  some  persons  is  so  strongly  marked  as 
to  render  them  susceptible  to  the  infection  more  than  twice,  even  as 


152  SMALLPOX 

often  as  five  or  six  times.  The  authenticity  of  reported  cases  of  this 
kind,  however,  is  not  to  be  taken  for  granted,  but  accepted  with  extreme 
caution,  as  there  are  many  sources  of  error. 

As  to  the  frequency  of  secondary  or  recurrent  smallpox,  there  is  some 
difference  of  opinion  on  the  part  of  authors.  Many  of  the  cases  reported 
in  the  olden  times  were  doubtless  based  upon  an  error  of  diagnosis,  for 
the  second  attacks  appear  to  have  occurred  almost  exclusively  in  children. 
Some  of  the  more  practical  writers  of  the  early  part  of  the  last  century 
hesitated  very  long  before  believing  that  it  was  possible  for  the  disease 
to  recur.  The  infrequency  of  such  cases  was  accurately  observed  during 
the  time  inoculation  was  in  vogue. 

Jenner,  who  closely  studied  casual  and  inoculated  smallpox  for  more 
than  thirty  years,  was  very  positive  in  his  views  as  to  the  permanency 
of  the  protection  which  one  attack  of  the  disease  conferred,  and  it  was 
doubtless  his  positive  convictions  on  this  point  that  led  him  to  announce 
his  oversanguine  belief  in  the  permanency  of  the  vaccine  influence. 

Gregory,  who  enjoyed  unusual  opportunities  for  studying  variola,  was 
very  incredulous  on  the  subject  of  recurrence  of  the  disease.  Most  of 
the  reported  cases  which  he  was  called  upon  to  examine  he  found 
incorrectly  reported.  Echthyma,  pustular  syphilis,  and  particularly 
varicella,  he  states  were  fruitful  sources  of  error.  But  few  patients 
claiming  to  have  had  smallpox  previously  came  under  his  care  as 
physician  to  the  vSmallpox  Hospital  of  London  for  more  than  twenty 
years,  and  of  these  few  only  a  very  small  fraction  could  stand  the  test 
of  rigid  scrutiny.  Koch  states  that  in  the  great  epidemic  of  1871-72, 
among  12,000  cases  of  smallpox  in  South  Germany,  no  second  attack 
occurred. 

Marson  is  responsible  for  the  statement  that  during  the  one  hundred 
and  nineteen  years  since  the  founding  of  the  London  Smallpox  Hospital, 
there  is  no  record  of  a  patient  having  been  admitted  twice,  suffering 
from  smallpox.  He  reports,  however,  the  following  interesting  instance 
of  recurrent  smallpox:  "An  Irishman,  the  son  of  a  medical  officer 
of  the  army,  who  had  been  vaccinated  in  infancy  by  his  father,  and 
who  had  a  large  cicatrix  remaining  from  the  vaccination,  and  who 
was  attended  by  his  father  for  smallpox  in  early  life  and  bore  decided 
pits  of  the  disease,  in  1844,  at  twenty-three  years  of  age,  was  admitted 
to  the  Smallpox  Hospital  with  severe  confluent  smallpox,  of  which  he 
died."  Marson  believes  that  exposure  for  a  time  to  a  great  change  of 
climate,  either  hot  or  cold,  seems  to  predispose  the  constitution  to 
receive  a  second  attack  of  smallpox. 

It  is  said  that  Grossheim  observed  a  light  form  of  variola  in  a  patient 
three  months  after  the  first  attack,  but  this  peculiar  case  was  the  only 
instance  of  recurrence  which  he  noted  among  22,641  in  the  German 
Military  Hospitals. 

In  regard  to  the  historic  case  of  Louis  XV.,  Gregory  has  the  following 
to  say:  "The  most  remarkable  case  of  recurrent  smallpox  on  record 
is  that  of  Louis  XV.,  King  of  France,  who  died  of  it  in  the  year  1774, 
at  the  age  of  sixty-four,  after  having,  as  it  is  alleged,  undergone  that 


77//';  ICTIOLOdY  OF  SMAfJJ'OX  1  Tjf} 

disease  casually  in  1724,  wlicn  Ik;  w;is  foiiitccn  years  of  a^c.  1  liavo 
been  at  soitk;  pains  to  iiiv(\sti<i;at(;  this  cas(i,  which  created  a  great  .sen- 
sation at  the  time,  has  becii  (juoted  over  and  over  again,  aiul  to  which 
great  importance  has  been  attached.  After  careful  inquiry  into  dates, 
the  character  of  the  incubative  stage,  and  the  course  of  the  eruption, 
I  convinced  myself  that  his  Majesty  never  had  small[)ox  in  early  lif<', 
and  that  the  primary  attack  was  varicella." 

We  have  seen  in  the  Municipal  IIos})ital  a  number  of  patients  wIkj 
claimed  to  have  had  smallpox  previously,  but  only  a  very  few  were  able  to 
show  anything  like  characteristic  pitting;  and  all  of  those  who  did  show 
such  evidences  of  a  previous  attack  had  the  disease  the  second  time  in 
the  mildest  possible  form — so  mild  indeed,  in  some  instances,  as  to  be 
scarcely  recognizable,  the  eruption  being  either  arrested  in  the  papular 
or  in  the  vesicular  stage.  We  have  never  seen  an  unmodified  or  even 
a  severe  case  of  smallpox  occur  in  a  person  who  was  deeply  and  charac- 
teristically pitted  from  a  previous  attack. 

Quite  recently  two  cases  of  undoubted  second  attacks  have  come 
under  our  observation:  one  was  a  woman,  aged  twenty-nine  years,  who 
had  a  severe  attack  of  smallpox  at  the  age  of  one  and  a  half  years. 
The  patient's  face  was  fearfully  scarred  and  seamed.  The  second  attack 
was  extremely  mild,  there  being  but  two  hundred  modified  lesions  upon 
the  entire  cutaneous  surface. 

The  second  case  was  a  man,  aged  fifty  years,  who  had  his  first  attack 
in  Scotland  at  the  age  of  three  years;  at  this  time  five  of  his  brothers 
died  of  the  disease.  The  patient  presented  a  number  of  superficial  pits 
about  the  face.  The  second  attack  was  accompanied  by  a  fairly  abun- 
dant eruption,  but  the  lesions  were  distinctly  modified.  He  had  never 
been  vaccinated. 

The  evidence  relied  upon  to  prove  the  occurrence  of  second  attacks 
is  usually  obtained  from  patients  themselves,  inasmuch  as  it  is  exceed- 
ingly rare  for  a  physician  to  observe  two  distinct  attacks  of  smallpox  in 
the  same  individual.  During  the  past  thirty-four  years,  in  which 
period  more  than  9000  cases  of  smallpox  have  been  treated  in  the 
Philadelphia  Municipal  Hospital,  no  person  has  been  twice  admitted 
suffering  from  the  disease.  In  view  of  all  that  has  been  said,  it  is  prob- 
able that  second  attacks  of  smallpox  are  much  rarer  than  is  generally 
supposed. 

Age. — Age  cannot  be  said  to  influence  the  predisposition  to  the 
disease,  as  it  is  naturally  present  at  all  periods  of  life,  from  earliest 
infancy  to  extreme  old  age.  If  aged  persons  are  found  less  susceptible 
at  all,  it  is  because  of  the  prophylactic  power  of  vaccination.  While 
nursing  infants  under  six  months  old  commonly  resist  the  infection 
of  measles  and  scarlet  fever,  they  are  nearly  always  susceptible  to  the 
infection  of  smallpox.  Even  the  foetus  in  idem  is  not  exempt  from  the 
danger  of  an  attack  when  a  pregnant  woman  suffers  from  the  disease. 
The  variolous  process  in  such  a  patient  is  exceedingly  likely  to  excite 
abortion  or  premature  delivery,  and  the  foetus,  or  child,  may  show 
evidence  of  the  disease  in  the  form  of  an  eruption.     Such  evidence  has 


154  SMALLPOX 

been  observed  as  early  as  the  fourth  month  of  fetal  life;  we  have 
ourselves  seen  a  sparse  eruption  in  the  vesicular  stage  upon  a  foetus 
expelled  at  four  months.  We  can  also  recall  several  instances  of 
children  born  at  or  near  term  with  the  smallpox  exanthem  present; 
in  one  case  it  had  advanced  to  the  pustular  stage  and  the  child  was 
born  dead.  In  another  case  the  child  was  born  at  eight  months,  with 
the  variolous  eruption  just  appearing,  and  died  when  the  pustular  stage 
was  reached.  It  is  an  acknowledged  fact  that  a  woman,  though  per- 
sonally immune,  may  give  birth  to  a  child  suffering  from  smallpox;  it 
is  not  improbable  in  such  cases  that  the  mother  has  passed  through  a 
variola  sine  exanthcmate. 

Sex. — The  predisposition  to  smallpox  is  certainly  not  influenced  by 
sex.  Of  course  in  every  epidemic  a  larger  number  of  male  patients  is 
received  into  smallpox  hospitals  than  females.  This  is  manifestly  due  to 
the  fact  that  men  are  by  reason  of  their  daily  occupation  exposed  to  a 
greater  extent  to  the  infection. 

During  the  last  epidemic  (1901-04)  quite  a  large  number  of  motor- 
men  and  conductors  employed  on  the  street  railway  were  admitted 
into  the  hospital.  Women,  on  the  contrary,  as  a  result  of  the  greater 
amount  of  time  spent  in-doors,  are  less  subjected  to  contact  with  infected 
individuals.  Of  7204  cases  of  smallpox  treated  up  to  1903,  in  the 
Philadelphia  Municipal  Hospital,  4598  were  males  and  2606  were 
females.  Under  the  same  conditions,  however,  males  and  females  are 
equally  susceptible  to  the  disease. 

Race.— There  is  some  difference  of  opinion  concerning  the  influence 
of  race  upon  susceptibility  to  smallpox.  Most  authors  agree  that  the 
predisposition  to  variola  is  more  marked  among  the  dark-skinned 
peoples,  particularly  the  negro  race.  There  is  no  doubt  that  when 
smallpox  prevails  epidemically  in  this  country  the  proportion  of  deaths 
to  cases  is  greater  among  the  negro  than  among  the  white  race;  but 
this  we  believe  is  owing  to  the  fact  that  there  is  greater  neglect  of  vacci- 
nation among  the  former.  In  our  experience  the  unvaccinated  cases  of 
each  race  have  perished  in  about  the  same  proportion. 

The  aboriginal  races  appear  to  receive  smallpox  in  a  most  virulent 
form  and  with  fearful  mortality.  When  smallpox  first  gained  entrance 
into  Mexico  it  spread  like  wild-fire,  exterminating  tribes  to  such  an 
extent  that  frequently  not  sufficient  survivors  were  left  to  bury  the 
dead.  Smallpox  has  also  proven  itself  frightfully  fatal  among  the 
Indian  tribes  of  North  America.  In  Quito  one  hundred  thousand 
natives  were  destroyed. 

Season. — Rhazes,  the  Arabian  physician,  who  wrote  in  900  a.d.,  says: 
"  I  am  to  mention  the  seasons  of  the  year  in  which  the  smallpox  is  most 
prevalent,  which  are  the  latter  end  of  the  autumn  and  the  beginning 
of  the  spring,  and  when  in  the  summer  there  are  great  and  frequent 
rains  with  continued  south  winds,  and  when  the  winter  is  warm  and 
the  winds  southerly." 

Sydenham  said  that  when  a  smallpox  epidemic  is  mild  it  begins 
about  the  vernal  equinox  (March  25th);  but  when  of  an  extended  and 


77//';  ICTIOUXIY  OF  SMALIJ'OX 


1-5 


dangerous  kind  it  hcf^ins  in  the  month  of  January.  'J'hese  general- 
izations are  seareely  borne  out  by  the  history  of  smallpox  visitations. 

In  England  the  smallpox  appears  to  be  most  prevalent  during  the 
first  six  months  of  the  year;  acteonJing  to  I'arkes,'  tlie  average  London 
mortality  from  smallpox,  from  obs<'rvations  coxciing  a  long  period  of 
years,  is  greatest  during  the  first  six  months  of  the  year,  rising  to  a 
maximum  toward  the  end  of  May  and  falling  through  June,  until  it 
descends  to  the  mean  line,  where  it  fluctuates  during  the  last  six  months, 
to  rise  again  in  December  or  January. 

\n  Philadelphia,  small])ox  during  epidemic  prevalence  almost  invari- 
ably increases  in  the  fall  of  the  year,  beginning  with  the  month  of 
September  or  October.  The  number  of  cases  then  steadily  rises,  reach- 
ing the  maximum  during  the  months  of  December,  January,  and  Febru- 
ary, and  then  declining  month  by  month  until  July  and  August,  wheii 
the  minimal  incidence  is  reached. 

While  in  temperate  climates  smallpox  is  essentially  a  cold-iveaiher 
disease,  the  reverse  is  said  to  be  true  in  tropical  countries.  The  malady 
in  such  localities  is  alleged  to  be  at  its  worst  in  the  hot  months  and  to 
improve  during  the  cooler  season. 

The  following  tables  indicate  the  monthly  number  of  smallpox 
patients  reported  during  the  three  large  epidemics  that  have  occuired 
in  Philadelphia  in  the  last  half  century: 


1871. 

1872. 

January    . 

13 

3130 

February  . 

6 

1794  . 

March 

4 

1247 

April .        .      . . 

8 

587 

May  . 

9 

401 

June  . 

11 

208 

July  . 

15 

66 

August 

58 

30 

September 

111 

13 

October     . 

.    1628 

18 

November 

.     2944 

11 

December 

.    3307 

10 

al     .       .       . 

8114 

7515 

Tot 

15,629 
1884. 

1880. 

1881. 

1882. 

1883. 

1885 

January    . 

.      47 

885 

321 

152 

30 

3 

February  . 

.      78 

711 

284 

131 

25 

1 

March 

.      39 

575 

198 

91 

21 

0 

April  . 

.      25 

658 

150 

76 

31 

3 

May    . 

.      28 

523 

106 

60 

23 

5 

June  . 

.      32 

406 

64 

45 

20 

2 

July    . 

.      30 

241 

36 

34 

6 

0 

August 

.      96 

155 

18 

45 

7 

0 

September 

.      75 

208 

30 

57 

5 

0 

October     . 

.    301 

186 

43 

27 

2 

0 

November 

.     382 

224 

47 

35 

6 

0 

December . 

.    719 

336 

127 

37 

11 

0 

1866 

5108 

1424 

790 

187' 

14 

Total 

9389 

1  Hygiene  and  Public  Health,  London,  1901. 


156  SMALLPOX 


1901.  1902.  1903.  1904. 

January 1  433  126  317 

February 1  314  125  148 

March 5  186  136  133 

April 17  111  68  100 

May      ., 10  84  125  85 

June 9  54  151  17 

July 14  47  137  2 

August 52  12  85  2 

September 116  15  42  0 

October 247  17  93  3 

November 304  11  242  8 

December 384  58  365  2 

Total 1160  1342  1695  817 


The  above  tables  show  a  remarkable  uniformity  in  the  rise,  cul- 
mination, and  decline  by  month  of  the  three  epidemics.  In  all  three 
the  epidemic  actually  began  in  August  and  continued  to  increase 
throughout  the  autumn,  reaching  a  culmination  in  December  and 
Jan-uary.  A  gradual  decline  then  occurred  during  the  spring,  falling 
to  the  lowest  level  during  the  summer  months. 

It  would  appear  from  a  study  of  these,  three  visitations  that  the 
maximum  intensity  of  epidemics  in  this  city  is  reached  during  the 
winter  months  of  the  first  year,  particularly  December  and  January. 
When  the  epidemic  extends  throughout  several  winters,  while  the 
highest  level  of  each  year  is  reached  during  the  cold  season,  there  is, 
as  a  rule,  a  gradual  decline  from  winter  to  winter  until  the  epidemic 
dies  out. 

This  is  well  illustrated  in  the  epidemic  beginning  in  1880.  The 
epidemic  beginning  in  1901  is,  however,  an  exception  to  this  general- 
ization. During  the  winter  of  1902-03  it  looked  as  if  the  epidemic  was 
dying  out,  but  during  the  following  winter  (1903-04)  it  acquired  renewed 
force  and  almost  equalled,  as  regards  the  number  of  persons  attacked, 
its  extent  in  the  winter  of  1901-02.  Indeed,  during  the  calendar  year 
of  1903  there  were  actually  more  cases  of  smallpox  in  the  city  than 
during  the  preceding  years. 

In  the  visitation  of  1871-72  the  force  of  the  epidemic  was  expended 
during  the  year  from  August,  1871,  to  August,  1872,  when  the  disease 
was  practically  exterminated.  Of  the  15,629  cases  which  occurred 
in  the  two  years,  15,476  developed  from  August  to  August. 

In  the  epidemic  which  began  in  1880  and  continued  for  four  or  five 
years,  of  the  total  number  of  9389  cases,  5502  occurred  during  the  first 
year  beginning  with  August. 

Even  in  the  epidemic  beginning  in  1901,  which  exhibited  a  recru- 
descence in  1903,  the  largest  number  of  cases  (2332)  developed  within 
the  year  from  August,  1901,  to  August,  1902. 

Influence  of  Atmospheric  Conditions. — Moore  says:  "It  would 
appear  that  the  critical  mean  temperature  in  regard  to  smallpox  is  50°  F. 
When  the  mean  temperature  falls  below  that  value,  the  disease  spreads; 
when  it  rises  above  it,  the  disease  wanes.  The  explanation  is  no  doubt 
to  be  found  in  the  fact  that  defective  ventilation,  overcrowding,  and  de- 


77/ 1<:  KTI 0 L () (,'  Y  <) / '  SM ALLI'O X  \  f, 7 

ficient    nutrition    wait  upon   cold     wcallicr,   ;iii(l     llicsc   arc    flic   most 
powerful  pro(lisposln<f  causes  ol"  smallpox  no  less  than  of  typhus." 

Ballard,'  eoiiuuentinj^  on  the  London  epidcniic;  of  1X70  71  wrote: 
"There  is  some  reason  for  believing  that  th(;  variations  of  the  epidemic 
(of  smallpox)  from  week  to  week  are  influenced  to  a  certain  extent  by 
atmospheric  conditions  and  more  especially  temperatnrc." 

Mr.  F.  W.  Alexander,'  Medical  Ofliccr  of  Hcidth  ol"  the  lK,rou;rli  of 
Poplar,  from  observations  miule  during  the  epidemic  of  1001  02,  con- 
eluded  that  the  meteorological  conditions  which  a]>j)carcd  to  favor  the 
spread  of  smallpox  were: 

(1)  Absence  of  sunshine;  (2)  presence  of  the  sun  aboNc  tlx;  horizfju 
for  less  than  eighty  hours  a  week — i.  e.,  less  than  eleven  hours  j>er  day; 
(3)  temperature  of  the  air  below  50°  F. ;  and  (4)  humidity  above  75° 
(the  saturation  point  being  taken  as  100°). 

The  Infection  of  Smallpox.— No  one  would  deny  at  the  present  day 
that  smallpox  is  due  to  a  specific  micro-organism.  There  is,  further- 
more, no  doubt  that  the  disease  is  spread  by  means  of  this  orgam'sm, 
which  is  reproduced  in  every  patient.  A  small  quantity  of  the  fluid 
from  a  pustule  inoculated  into  an  unprotected  person  gives  rise  to  the 
disease;  this  is  conclusive  proof  of  the  fact  that  the  germ  is  resident  in 
the  pustules.  It  is  also  present  in  the  exhalations  from  the  patient  and 
in  the  blood.  Ziilzer  proved  that  it  is  contained  in  the  blood  by  success- 
fully inoculating  a  monkey  with  blood  taken  from  a  smallpox  patient. 
It  would  appear  from  the  experiments  of  the  older  waiters  that  the 
physiological  secretions  and  excretions,  the  saliva,  sputum,  urine,  feces,' 
etc.,  are  not  in  themselves  infectious;  w^hen,  however,  they  become 
contaminated  with  particles  derived  from  the  skin  and  mucous-membrane 
lesions,  they  doubtless  acquire  an  infectiousness. 

The  contagium  emitted  by  a  patient  is  most  intense  in  his  immediate 
vicinity,  but  it  may  be  transported  in  an  active  state  for  some  distance 
by  the  atmosphere.  If  a  susceptible  person  should  enter  a  poorly 
ventilated  small  apartment  containing  one  or  more  severe  cases  of 
smallpox,  infection  would  almost  certainly  occur,  while  if  the  apartment 
were  large  and  well  ventilated  and  the  cases  few  and  mild,  the  risk  of 
infection  would  be  diminished;  if  he  should  approach  equally  near  the 
same  patient  in  the  open  air,  the  risk  would  be  still  less. 

Infectious  Period  of  Smallpox. — Smallpox  is  undoubtedly  infectious 
in  all  stages  characterized  by  symptoms.  It  is  alleged  by  some  that 
the  disease  is  even  infectious  during  the  period  of  incubation,  but  we 
think  there  is  very  little  reason  to  believe  that  such  is  the  case.  It  is 
possible,  however,  that  the  blood  of  an  individual  at  this  stage  might 
convey  the  infection  if  it  w^ere  introduced  into  the  system  of  a  susceptible 
person. 

Schafer,  quoted  by  Cursclimann,  reports  an  interesting  case  in  this' 
connection:    "In  the  Charity  Hospital  of   Berlin  small  pieces  of   skin 
were  taken  for  transplantation  upon  other  individuals  from  the  ampu- 

1  Medical  Times  and  Gazette,  March  11,  1S71.  =  Abstract  in  Lancet,  October  -l,.  1902. 


158  SMALLPOX 

tated  arm  of  a  person  who,  before  and  at  the  time  of  the  amputation, 
did  not  manifest  the  shghtest  symptoms  of  general  disease.  Several 
hours  after  the  amputation  the  patient  was  attacked  with  violent  fever, 
followed  two  days  later  by  the  eruption  of  smallpox.  One  of  the  indi- 
viduals upon  whom  the  transplanted  skin  had  been  placed  was  attacked 
by  variola  on  the  sixth  day  after  the  operation.  The  three  others 
remained  exempt. 

The  disease  is  least  infectious  during  the  initial  stage  and  most  highly 
so  during  the  suppurative  and  early  period  of  the  desiccative  stages. 
The  scabs  are  unquestionably  infectious,  and  as  long  as  these  remain 
on  the  skin  the  patient  should  be  regarded  as  dangerous  to  the  com- 
munity. Apart  from  the  experience  of  modern  observers,  evidence  of 
the  infectiousness  of  the  crusts  is  found  in  the  ancient  custom  in  vogue 
among  the  Chinese  of  inoculating  smallpox  by  inserting  the  crusts  in 
the  nose. 

Even  after  death  the  body  retains  the  power  of  transmitting  the 
contagium.  This  fact  has  been  demonstrated  more  than  once  where 
public  funerals  have  not  been  interdicted,  and  where  bodies  of  persons 
who  have  died  of  smallpox  have  by  accident  found  their  way  into 
dissecting  rooms.  It  is  said  that  a  corpse  may  retain  the  infection  in  a 
condition  to  transmit  the  disease  for  an  indefinite  period — even  for  the 
almost  incredible  period  of  several  years. ^ 

Austin  Flint  records  an  interesting  case  in  which  the  disease  was 
spread  by  a  cadaver: 

"During  the  winter  of  1848-49,  a  young  man,  a  member  of  the 
Medical  Class  of  the  New  York  University,  died  suddenly  and  un- 
expectedly in  the  night  under  the  care  of  a  physician  who  had  not 
thought  him  seriously  ill.  I  was  invited  to  the  autopsy,  and  observed, 
when  the  corpse  was  uncovered,  a  few  dark-red  spots  on  the  surface, 
which  were  supposed  to  be  petechial,  the  principal  symptoms  of  his 
attack  having  been  gastric,  with  great  debility,  as  we  were  informed. 
The  coffin  was  taken  to  a  New  England  village  for  burial,  where  at  the 
funeral  some  of  the  relatives  approached  and  opened  it  to  see  the  face 
of  the  deceased  before  it  was  inhumed.  Of  this  number  eight  were 
attacked  with  smallpox,  no  other  person  in  the  neighborhood  being 
assailed." 

The  infection  of  smallpox  may  be  conveyed  in  the  following  ways: 

1.  Through  direct  exposure  to  the  patient,  or  to  infected  secretions 
and  excretions. 

2.  Through  contact  with  objects  which  have  been  infected  by  the 
patient — for  example,  sick-room  articles. 

3.  Through  infection  carried  in  the  clothing  or  on  the  person  of 
healthy  individuals. 

4.  Through  air  transmission. 

5.  Through  transmission  by  insects  and  domestic  animals. 
Infection  through  Direct  Exposure  to  the  Patient. — The  vast  majority 

of  cases  of  smallpox  result  from  exposure  to  individuals  suffering  from 

1  Vide  Nouveau  Dictionary,  article  Contagion. 


77//';  i<:r[()ij<)()  v  of  sma  ijj'ox  1 5U 

the  disease.  Smallpox  is  the  most  typical  exam[>lc  oi  the  fontagious  op 
catching  disease.  The  briefest  possible  exposure  on  the  part  of  a 
susceptible  person  will  suffice  to  fjroduce  the  disease.  Many  victims 
never  discover  the  source  of  their  infection;  this  is  not  s<i  surprising  when 
we  appreciate  the  fact  that  the  patient  may  imjjart  the  disease  before- 
the  appearance  of  the  eruption.  That  smallpox  may  be  transmitted 
during  the  initial  stage  is  undoubtedly  proven  by  the  records  of  cases 
in  which  the  infection  was  received  from  individuals  suffering  from 
variola  sine  exanthematc.  Persons  are  also  frequently  exposed  to 
patients  suffering  from  extremely  mild  and  unrecognized  forms  of 
smallpox.  The  patients  may  not  deem  themselves  ill  and  may  after 
the  initial  illness  continue  their  daily  labors,  in  this  manner  unconsciously 
endangering  the  health  of  those  with  whom  they  come  in  contact.  We 
recall,  during  the  mild  epidemic  of  smallpox  of  several  years  ago,  a 
negro  who  drove  a  carriage  along  one  of  the  principal  thoroughfares  of 
this  city,  who,  though  in  the  pustular  stage  of  smallpox,  did  not  feel 
sufficiently  ill  to  remain  at  home.  Time  and  time  again  have  we  Vjeen 
informed  by  patients  that  they  came  to  the  hospital  in  street  cars. 
Some,  too,  admitted  having  travelled  on  the  railroad  from  cities  more 
or  less  distant  while  suffering  from  the  disease  in  its  early  stages. 

The  fact  is  conclusively  proven  that  the  degree  of  severity  of  the 
attack  produced  in  the  second  person  bears  no  relationship  to  that  in 
the  infecting  individual.  We  recall  the  case  of  a  fatal  hemorrhagic 
smallpox  in  a  pregnant  woman  who  received  the  infection  from  her 
father-in-law,  whose  attack  was  so  mild  as  to  escape  unrecognized. 
There  are  on  record  reports  of  a  few  epidemics  in  which  smallpox  was 
uniformly  mild,  but  ordinarily  the  severity  of  an  attack  of  smallpox  is 
measured  by  the  susceptibility  of  the  victim. 

A  robust  constitution  is  no  safeguard  against  variolous  infection;  in 
fact,  some  writers  consider  persons  in  good  health  more  susceptible  to 
the  disease,  on  the  same  principle  that  ruddy  children  take  vaccination 
more  easily  than  weaklings. 

Sometimes  extensive  epidemics  arise  from  the  importation  into  the 
community  of  a  single  patient  suffering  from  the  disease.  One  of  the 
most  remarkable  instances  of  rapid  diffusion  of  smallpox  is  the  epidemic 
in  Montreal  in  1885,  recorded  by  Osier.  The  city  was  visited  by  small- 
pox from  1870  to  1875,  after  which  it  died  out,  owing  to  vigorous  vacci- 
nation and  the  exhaustion  of  suitable  material.  For  ten  years  the  city 
remained  free  of  the  disease.  The  French  Canadians,  being  as  a  class 
opposed  to  vaccination,  a  large  unvaccinated  population  grew  up  in 
this  period.  On  February  28,  1885,  a  Pullman  car-conductor,  who  had 
arrived  from  Chicago,  where  smallpox  was  prevalent,  was  removed  to 
the  Hotel  Dieu,  the  civic  smallpox  hospital  being  at  that  time  closed. 
Isolation  was  not  practised,  and  as  a  result  a  servant  in  the  hospital 
contracted  the  disease  and  died.  After  this  occurred,  *'  with  a  necrliaence 
absolutely  criminal,  the  hospital  authorities  dismissed  all  patients  who 
presented  no  symptoms,  who  could  go  home."  The  disease  spread  like 
fire  in  dry  grass,  and  within  nine  months  3164  persons  died  of  smallpox 


160  SMALLPOX 

Infection  through  Sick-room  Objects. — While  the  contagium  of  small- 
pox is  perhaps  more  commonly  conveyed  from  person  to  person  through 
the  atmosphere,  this  is  by  no  means  the  only  medium  of  infection.  The 
infecting  germs  become  attached  to  all  objects  in  the  immediate  vicinity 
of  the  patient,  and  cling  to  them  for  a  variable  period  of  time.  Objects 
which  have  a  rough,  shaggy  surface,  such  as  blankets,  woollen  clothing, 
etc.,  not  only  become  more  intensely  infected,  but  hold  the  infection 
much  longer  than  smooth  objects.  Woollen  garments  closely  packed  and 
excluded  from  the  air  as  completely  as  possible  have  been  known  to 
retain  the  infection  for  many  months  or  even  years.  If,  however,  such 
garments  be  freely  exposed  to  the  atmosphere  and  sunlight,  the  con- 
tagium will  soon  be  destroyed.  Of  course  it  may  be  destroyed  at  once 
by  disinfecting  agents. 

Buck^  recounts  the  history  of  a  case  which  illustrates  the  persistence 
of  variolous  infection.  In  1876  a  child  was  treated  for  an  attack  of 
smallpox  in  a  New  York  house,  after  which  the  sick-room  was  thoroughly 
disinfected,  the  walls  washed,  and  the  carpets  removed.  Two  years 
later  (1878)  an  unvaccinated  two  months'  old  child  of  new  tenants 
occupying  the  same  room  fell  ill  with  smallpox,  although  it  had  never 
been  out  of  the  apartment.  No  smallpox  was  present  in  New  York 
at  the  time. 

Infected  objects  may  convey  the  contagium  over  long  distances,  even 
over  many  hundreds  of  miles.  In  1898  we  saw  a  case  of  smallpox  in 
this  city  in  which  we  believe  the  infection  was  received  from  a  bale  of 
cotton  brought  from  the  South.  Smallpox  was  prevalent  in  the  cotton- 
growing  districts  of  the  Southern  States,  and  was  of  such  a  mild  type 
that  the  negro  patients  would  frequently  be  in  the  fields  gathering  cotton 
while  the  eruption  was  developing  or  the  scabs  dropping  off. 

The  case  occurred  in  a  man  employed  in  a  Philadelphia  mill  where 
cotton  goods  were  manufactured,  and  which  had  received  cotton  from 
the  South.  At  the  time  no  cases  of  smallpox  were  present  in  Philadelphia 
or  its  vicinity,  nor  had  there  been  for  a  period  of  two  or  three  years. 
The  man  had  not  been  out  of  the  city  for  a  long  time.  In  seeking  for 
the  source  of  the  infection  we  could  arrive  at  no  other  conclusion  than 
that  it  had  been  derived  from  a  bale  of  cotton. 

Infection  Carried  by  Healthy  Individuals. — Not  only  objects  in  the 
room,  but  also  healthy  persons  whose  duties  require  them  to  come  in 
contact  with  the  sick,  may  be  the  means  of  communicating  the  infection. 
The  infection  may  adhere  to  the  hair,  the  hands,  and  other  parts  of  the 
body  of  the  attendants,  but  the  chief  danger  is  from  their  clothing. 

That  healthy  individuals  may  carry  the  infection  has  been  conclusively 
demonstrated  to  us.  We  have,  on  a  number  of  occasions,  had  brought 
into  the  hospital  infants  suffering  from  smallpox  who  had  not  been  out 
of  their  homes,  and  who  lived  in  neighborhoods  free  of  the  disease. 

Great  caution  should  be  observed  by  physicians,  nurses,  and  others 
in  attendance  upon  smallpox  patients.    The  exercise  of  proper  care  will 

1  Treatise  on  Hygiene,  New  York,  1879. 


77//';  KTIOIJXl  Y  OF  SMA  LLI'OX  161 

rculucc  tli(^  (tliaiK'CS  of  carryiiifj;  iiifcclioii  lo  ;i  niiiiiiiiiini.  'I'lic  writers 
have  come  in  contact  witii  tlionsaiids  of  ,sniall|)(jx  patients,  but  by  tlie 
exercise  of  great  care  have  never  to  tlieir  knowledge  conveyed  the 
disease  to  a  single  incHvichial. 

Air   Transmission   of   Smallpox   Infection. — The   contagium   given    off 
from  a  patient  suffering  from  smallpox  is  of  a  volatile  character,  ca[)al>l(r 
of   surcharging  the  a,tmos|)here  of  the  sick-room.      The  older  writers 
believed  that  the  sphere  of  contagious  influence  of  small[)ox  was  ex- 
tremely limited. 

Haygarth,  quoted  by  Gregory,  was  of  the  opin'on  that  it  did  nf^t 
extend  "more  than  a  few  feet  from  the  patient's  })ody." 

Ilirsch  says  that  the  small{)()x  contagion  "can  be  spread  by  atmos- 
pheric currents  within  a  small  range,"  and  that  there  is  "no  mathe- 
matical expression  to  be  found  for  the  extent  of  that  range;  at  the 
utmost  it  extends  no  farther  than  the  immediate  surroundings  of  the  sick." 

English  physicians  have  within  recent  years  devoted  considerable  study 
to  the  determination  of  the  striking  distance  of  the  disease. 

In  the  epidemic  of  1881,  Mr.  W.  H.  Power,*  after  excluding  all 
possible  infection  through  ordinary  intercourse,  formulated  an  hypothesis 
of  atmospheric  convection  of  the  smallpox  poison.  He  assumerl  that 
smallpox  infective  material  was  "particulate,"  and  that  certain  favorable 
conditions  could  disseminate  such  particulate  matter  over  an  area  of  a 
quarter  or  half  a  mile. 

The  particulate  matter,  or  infectious  dust,  may  be  held  in  suspension 
in  the  water  particles  in  the  air,  in  fog  and  mist,  and  may  be  driven  l)y 
air  currents  and  deposited  at  some  distance.  During  periods  of  still- 
ness of  the  air  about  the  hospital  the  infection  is  taken  up  and  then 
wafted  by  the  winds.  The  absence  of  ozone  in  the  atmosphere  is  also 
said  to  be  favorable  to  spread  of  infection.  Periods  of  small  move- 
ment of  air  and  absence  of  ozone  are  said  by  INIr.  Power  to  have 
preceded  each  of  the  more  notable  epidemic  extensions  in  the  neigh- 
borhood of  the  Fulham  Hospital. 

Parkes^says:  "The  exceptional  incidence  of  smallpox  in  the  immediate 
neighborhood  of  some  of  the  London  Smallpox  Hospitals  can  admit 
of  but  one  explanation,  viz.,  that  when  a  sufficient  number  of  cases  in 
the  acute  stages  are  collected  together  in  one  building  on  a  small  area 
of  ground,  the  hospital  becomes  a  centre  of  infection  to  the  surrounding 
neighborhood."     (See  Fig.  20.) 

"As  regards  the  number  of  cases  aggregated  in  a  hospital  necessary 
to  enable  it  to  exert  an  influence  on  the  surrounding  neighborhood, 
Dr.  Power's  reports  of  1884-85  show  that  this  influence  was  exerted 
when  the  number  of  acute  cases  had  been  restricted  to  twenty,  while 
on  one  occasion  he  found  the  excess  of  smallpox  in  the  neighborhood 
of  the  Fulham  Hospital  was  quite  remarkable  at  a  time  when  the  total 
admissions  to  the  hospital  had  not  exceeded  nine,  only  five  of  these 
being  cases  in  an  acute  stage." 

1  Supplement  to  Local  Government  Board,  lSSO-81,  also  1SS4-S5. 
-  Hygiene  and  Public  Health,  London,  1901. 
11 


162 


SMALLPOX 


Mr.  A.  W;  Blyth^  remarks.  "The  usual  spread  of  smallpox  is  from 
person  to  person,  but,  from  inquiries  which  have  taken  place  as  to  the 
influence  of  smallpox  hospitals  upon  a  surrounding  population,  it  is 
certain  that  the  infection  can  strike  at  a  distance. 


Special  area  around  Fulham  Hospital  divided  into  sections  of  li,%,  ^,  and  1  mile  radii,  show- 
ing in  the  different  areas  the  number  of  houses  (out  of  every  100)  invaded  by  smallpox  from  May 
25,  1884,  to  September  26,  1885. 

Between  N.  and  W.  the  hospital  was  greatly  isolated  from  traffic  because  of  few  roadways. 

Belt  of  houses  between  W.  and  S.  comparatively  narrow. 

Between  N.  and  E.  houses  few  within  34  mile ;  beyond  they  completely  encompass  the  hospital. 

The  so-called  special  area  was  within  500  feet  from  the  hospital  centre. 

The  influence  of  the  Sheffield  Hospital  in  the  epidemic  of  1887-88 
could  be  distinctly  traced  for  a  circle  of  four  thousand  feet :  the  following 
percentages  of  households  attacked  at  successive  distances  from  the 
hospital  are  given  in  the  original  reports  by  Dr.  Barry,^  inspector  of 
the  Local  Government  Board  for  England: 


0  to   1000  feet 1.75  1 

1  "    2000    " 0.50  j 

2  "     3000    " 0.14    \ 

3  "    4000     " 0.05   I 

Elsewhere 0.02  J 


Percentage  of  houses  attacked 
at  varying  distances  from 
Sheffield  Hospital. 


The  possibility  of  smallpox  spreading  by  aerial  infection  increases 
greatly  both  the  hospital  difficulty  and  that  of  individual   isolation." 

1  Manual  of  Public  Health. 

2  Report  of  an  Epidemic  of  Smallpox  at  Sheffield,  1887-88 ;  London,  1889. 


nil':  KTioLodY  of  smalIjI'ox 


163 


Evans,'  from  ohscirvatioii  of  <a  .sinallj)ox  f'j)i(lciiiic  nt  l>r;i(lfon!,  came 
to  the  .same  eoricliisioii  ;i,.s  l>;irry.  I)iiriii<i;  tlic  year  1S(K},  iVH)  flomifilfs 
were  attacked  by  smallpox  within  a  rachiis  of  a  mile  of  ttic  IJradffjrd 
Fever  Hospital. 

There  were  17,()()()  lioiiscs  in  tlie  one-mile  area  about  the  hospital; 
of  the  02G  honses  newly  attacked,  1()2  were  located  within  th<- (piarter- 
mile  limit,  242  between  the  (piartcr-mih;  and  tiic  half-mii(;  boundaries, 
and  59  within  the  three-(juarter-mile  and  one-mile  limit.  The  rate  of 
incidence  of  smallpox  in  100  houses  in  the  whole  borouj^h  was  1.6;  in 
the  special  one-mile  area  about  the  hospital,  3.0;  and  in  the  rcmainrjcr 
of  the  borough,  0.0. 


Diagram  showing  the  influence  of  the  wind  in  disseminating  smallpox.    (Evans.) 

Within  the  quarter-mile  circle  about  the  hospital  the  rate  was  10.4 
per  cent.;  between  the  half-mile  and  the  three-quarter-mile,  2.1  per  cent. 
Evans  beheves  that  the  extensive  prevalence  of  smallpox  within  the 
special  area  about  the  hospital  is  to  be  explained  on  the  grounds  of 
aerial  transmission  of  infected  material  from  the  wards  of  the  hospital. 

This  view  he  believes  is  confirmed  by  a  study  of  the  direction  of  the 
prevailing  winds  during  the  year  1893. 

Evans  calculated  the  percentage  of  infected  houses  in  the  four  quad- 
rants of  the  circular  mile  area  about  the  hospital  as  follows: 

Northeast  quadrant 7.06  per  cent. 

Southeast         "  5.28 

Northwest        "  2.40        " 

Southwest        '•  -.93 

1  British  Medical  Journal,  1894,  vol.  ii.  pp.  356-358.    Quoted  by  Moore. 


164  SMALLPOX 

"These  figures,"  he  says,  "are  readily  explained  by  the  fact  that  on 
250  days  of  the  year  the  prevailing  winds  were  westerly,  and  only  on 
83  days  was  the  wind  persistently  from  the  east. 

"  During  the  first  half  of  the  year,  when  easterly  winds  were  more  com- 
mon than  during  the  second  half,  the  proportion  of  cases  occurring 
on  the  western  side  of  the  hospital  was  relatively  greater  than  during 
the  remainder  of  the  year,  when  the  easterly  winds  were  less  fre- 
quent.", 

'  Thresh,^  from  a  study  of  smallpox  outbreaks  in  the  neighborhood 
of  the  smallpox  hospital  ships  in  the  Thames  River,  says:  "The  extent 
of  the  area  around  a  smallpox  hospital  which  may  be  affected  directly 
and  indirectly  by  the  hospital  is  apparently  much  larger  than  has  here- 
tofore been  supposed.  In  the  case  of  the  ships  lying  off  Purfleet  the 
influence  is  probably  being  felt  at  a  distance  of  fully  three  miles,  and 
the  presence  of  a  belt  of  water  half  a  mile  in  width  is  powerless  to  arrest 
the  contagion. 

"There  can  be  no  doubt  that  the  danger  increases  with  the  increase 
of  the  number  of  acute  cases  in  the  hospital,  the  infectivity  not  being 
marked  until  a  certain  degree  of  concentration  is  reached,  and  with 
the  proximity  to  the  hospital.  With  a  small  hospital  (say,  constructed 
for  from  ten  to  twenty  or  thirty  cases),  my  impression  is  that  there  is  but 
little  danger  of  the  disease  being  spread  therefrom;  but  the  danger  can- 
not be  said  to  be  non-existent. 

"With  hospitals  having  100  beds  or  more  the  danger  is  naturally 
much  greater,  and  when  we  come  to  hospitals  of  the  size  of  those  required 
to  cope  with  an  epidemic  in  a  large  city  the  peril  may  be  great  indeed." 

He  further  says:  "The  hospital  ships  were  placed  opposite  Purfleet 
in  1884,  and  since  that  time  there  has  been  an  excessive  prevalence  of 
smallpox  in  the  Orsett  district,  and  especially  in  that  portion  lying- 
nearest  the  ships.  Prior  to  these  floating  hospitals  being  established 
near  Purfleet,  smallpox  was  little  more  prevalent  in  the  Orsett  district 
than  in  the  remainder  of  the  county,  and  only  one-third  to  one-fourth 
as  prevalent  as  in  the  metropolis. 

"The  change  since  then  has  been  most  marked:  from  the  same  basis 
the  disease  has  been  seven  times  more  prevalent  in  Orsett  than  in  the 
remainder  of  the  county,  and  two  and,  one-half  times  more  prevalent 
than  in  London." 

Dissenting  Views  as  to  the  Atmospheric  Transmission  of 
Smallpox  Infection. — Certain  writers  dissent  from  the  view  above 
expressed  as  to  the  aerial  convection  of  smallpox. 

Seaton^  believes  that  no  adequate  evidence  has  been  adduced  to 
prove  aerial  convection  for  hospitals  situated  in  sparsely  settled  dis- 
tricts. 

He  speaks  of  an  instance  which  came  under  his  observation  in  which 
a  number  of  unvaccinated  children  living;  within  a  stone's  throw  of  a 
smallpox  hospital  did  not  take  the  disease  until  a  child  sick  with  small- 

1  The  Lancet,  February  22  and  26,  1902.  British  Medical  Journal,  January,  1896,  p.  582. 


77//';  i<:ti<)L()(iy  of  smallpox  165 

pox  was  hroiight  to  IIk-  house,  iiiid  llic  iiii vacciii;ilf(l  cliildif  n  ihiis 
directly  exposed  to  the  eoiita^ion.  This  was  re^^arded  as  evid(;iiee  tliat 
the  contagion  of  smallpox  does  not  extend  to  any  considerable  distance 
through  the  air/ 

Savill^  holds  "that  fresh  air,  being  itself  one  of  the  })est  natnr;d  germ- 
icides, is  very  unlikely  to  become  a  vehicle  for  the  conveyance  of  microbes, 
and  that  on  a  'priori  grounds,  therefore,  we  would  not  ex|)ect  the  germs- 
of  smallpox  to  be  carried  beyond  the  limit  of  an  ordinary  room." 

He  carefully  investigated  the  epidemic  of  smallpox  at  Warrington 
in  1892-93,  which  he  reported  to  the  Royal  Comission  on  Vaccination, 
and  concluded  that  there  was  no  need  to  assume  a  theory  of  aerial  con- 
vection to  explain  the  spread  of  the  disease. 

Wallace,"''  in  discussing  this  epidemic,  comments  on  some  of  the  obser- 
vations presented  in  Savill's  report.  He  points  out  that  aerial  convec- 
tion would  not  explain  the  spread  of  the  epidemic,  for  (1)  the  numbers 
of  infected  houses  do  not  work  out  in  perfect  keeping  with  a  theory  of 
proportionate  distances  from  the  hospital  as  a  centre,  and  (2)  the  largest 
proportion  of  infected  houses  is  not  to  be  found  in  the  quadrant  oppo- 
site the  prevailing  winds. 

Experience  of  Philadelphia  during  the  Epidemic  of  1901  to 
1904. — During  the  years  1901,  1902,  and  1903  there  occurred  in  the. 
city  of  Philadelphia  3989  cases  of  smallpox.  Throughout  the  entire 
epidemic  the  Twenty-eighth  Ward,  in  which  the  INIimicipal  Hospital 
was  located,  furnished  by  far  the  largest  number  of  smallpox  patients. 
Next  to  this  ward,  in  smallpox  incidence,  came  those  adjoining  it.  In 
the  Twenty-eighth  Ward  there  were  144  cases  of  smallpox  per  10,000 
of  population.  In  the  entire  city,  exclusive  of  this  ward,  the  rate  was 
29  per  10,000  of  population.  The  Twenty-eighth  Ward  and  several  of 
the  neighboring  wards,  representing  26.71  per  cent,  of  the  population, 
contained  53.67  per  cent,  of  the  smallpox  cases. 

Although  we  were  at  first  skeptical  concerning  the  aerial  transmission 
of  variolous  infection  from  a  smallpox  hospital,  the  preponderating 
incidence  of  smallpox  in  the  INIunicipal  Hospital  district  and  adjoining 
wards  throughout  the  entire  epidemic  has  forced  us  to  accept  this  mode 
of  dissemination  of  the  disease  as  established. 

Transmission  by  Insects  and  Domestic  Animals. — Researches  within 
recent  years  have  established  the  fact  that  insects  may,  in  a  number  of 
diseases,  directly  convey  infection  to  the  human  subject.  The  infective 
agent  may  undergo  evolutional  development  in  the  insect,  the  creature 
thus  acting  as  an  intermediate  host,  or  it  may  be  carried  upon  the  wings 
and  feet. 

In  the  warmer  months  of  the  year  the  common  house  fly  abounds  in 
the  wards  of  hospitals.  This  insect  is  essentially  a  scavenger,  and  is 
particularly  attracted  by  foul-smelling  pus.  It  is  a  common  sight  in 
the  summer  season  to  observe  swarms  of  flies  foraging  upon  the  purulent 
material  upon  the  faces  and  bands  of  smallpox  patients,  the  wings  and 

1  British  Medical  Journal,  August  5,  1882.  -  Ibid.,  1897,  p.  16S0. 

s  James  Wallace,  Smallpox,  London,  1902. 


166  SMALLPOX 

feet  of  the  insects  being  frequently  bathed  in  the  contents  of  ruptured 
pustules. 

We  have  undertaken  investigations  to  determine  whether  or  not  the 
flies  swallow  the  purulent  material.  Repeated  microscopic  examina- 
tions of  the  intestines  of  flies  caught  in  the  vicinity  of  smallpox  patients 
demonstrated  the  presence  of  an  abundance  of  streptococci  and  staphylo- 
cocci, which  are  the  predominating  organisms  in  the  late  variolous 
pustules.  These  germs  did  not  appear  to  be  digested,  for  they  took  the 
ordinary  stains  well.  The  intestines  of  flies  caught  about  ordinary 
households,  on  the  other  hand,  contained  no  germs  of  this  character, 
and,  indeed,  often  no  germs  at  all.  Inasmuch  as  the  causal  parasite 
of  smallpox  is  resident  within  the  pustules,  it  is  reasonable  to  suppose 
that  it  also  is  swallowed  by  the  fly. 

It  is  obviously  impossible  to  present  proof  that  flies  transmit  the  infec- 
tion of  smallpox;  but  that  they  are  capable  of  doing  so  appears  strongly 
probable.  A  fly  carrying  upon  his  feet  or  wings  the  contagium  vivum 
of  variola  would,  on  aHghting  upon  a  susceptible  individual,  offer  every 
opportunity  for  infection.  It  is  also  possible  for  the  swallowed  germs 
to  be  deposited  in  the  form  of  excrement  upon  the  face  or  hands  of  an 
unprotected  person. 

The  ordinary  house  fly,  or  Musca  domestica,  is,  owing  to  the  conforma- 
tion of  the  mouth  parts,  incapable  of  biting.  A  form  of  stable  fly,  the 
Stomoxys  calcitrans,  frequently  found  in  houses,  does,  however,  pierce 
the  skin.  Such  a  fly  might  readily  carry  the  infection  of  smallpox  into 
the  skin  in  the  act  of  biting,  and  thus  give  rise  to  an  inoculation  form 
of  smallpox. 

To  what  extent  flies  and  other  insects  contribute  toward  the  spread 
of  smallpox  cannot  be  determined.  As  flies  are  capable  of  travelling 
a  considerable  distance,  some  cases  of  smallpox  of  mysterious  origin 
might  be  explained  through  their  agency. 

That  the  transmission  of  smallpox  through  the  medium  of  flies,  how- 
ever, is  not  an  important  factor  in  epidemics  is  evidenced  by  the  fact 
that  the  disease  spreads  most  in  the  cold  months,  when  flies  are  absent, 
and  least  in  the  hot  months,  when  they  are  abundant. 

It  is  quite  conceivable  that  dogs,  cats,  and  other  domestic  animals 
occupying  domiciles  in  which  smallpox  exists  may  carry  the  contagion 
of  the  disease  in  their  fur.  The  closer  the  contact  of  such  animals  with 
the  variolous  patient,  the  greater  is  the  likelihood  of  particulate  infec- 
tion being  transferred.  The  roving  of  these  animals  might  play  some 
role  in  the  dissemination  of  the  disease  within  limited  areas. 

THE  SYMPTOMATOLOGY  OF  SMALLPOX. 

Period  of  Incubation. — From  the  moment  that  the  microparasite 
of  smallpox  is  received  into  the  system  certain  subtle  and  unknown 
processes  begin  which,  in  the  course  of  a  more  or  less  constant  period 
of  time,  culminate  in  active  clinical  manifestations.  To  this  latent 
breeding  stage  the  term  "  period  of  incubation"  is  applied.    The  time 


THE  8YMPT0MA  TOLOr;  Y  OF  SMA  LfJ'OX  ]  (;7 

ela}),sin(ij  between  the  reception  of  the  vjiriolfjus  [>oi.sf>n  iuu\  tlie  rjiifhrcak 
of  the  disease  can  oc(;asionally  he  detennined  witli  a  fonsidcrahh; 
degree  of  accuracy,  ^riiis  is  more  easily  accomph'shed  in  sj)oradic 
cases,  where  an  indivi(hial  has  l)een  exposed  bnt  once  and  for  a  brief 
period  of  time.  Where  the  exj)osure  is  frccjnent  or  extends  f>ver  a  long 
period  it  is  (hfficult  to  (h'vine  the  exact  moment  when  the  infection  is 
received.  When  the  (hsease  prevails  in  epidemic  form  it  is  not  impos- 
sible for  an  unknown  exposure  to  precede  the  one  of  which  the  indi- 
vidual has  knowledge;  in  such  cases  the  com])nted  [X'riod  of  incubation 
would  appear  to  be  unusually  short.  Erroneous  calculatif)ns  f)f  tlie 
duration  of  the  period  of  incubation  have  (ioul)tless  arisen  from  fnihire 
to  recognize  this  fact. 

In  the  majority  of  cases  in  which  we  have  had  the  opportunity  of 
carefully  studying  the  incubation  stage,  we  have  found  it  to  1>P  t*^"  j^} 
twej^g, dia.yS7  xind  we  would,  with  other  writers,  regard  this  as  the  normal  - 
period.     In  a  few  instances  it  is  true  we  have  known  persons  to  fall  ill 
with  smallpox  after  the  raising  of  a  two  weeks'  quarantine  of  the  houses 
in  which  they  were  confined  and  in  which  smallpox  had  existed.     W^e 
have  also  been  able  in  a  few  cases  to  reckon  with  tolerable  certainty 
a  period  of  incubation  of  sixteen  days,  the  eruption  appearing  on  the 
eighteenth.     Some  writers  have  recorded  instances  in  which  the  incu-_ 
bation  period  has  been  prolonged  to  twenty  days.    On  the  other  hand, 
we  have  known  a  young  physician,  exposed  to  smallpox,  to  develop  the 
first  symptoms  at  the  end  of  five  and  a  half  days,  and  the  eruption  at 
the   termination  of  ten  and  one-half  days.      Ordinarily,  however,  the  . 
period  is  seldozii, less. than  eight  days  or  more  than  fourteen. 

The  incubation  period  is  ordinarily  not  characterized  by  any  active 
symptoms.  Patients  usually  pursue  their  daily  occupations  ignorant 
of  the  fact  that  there  is  developing  within  them  a  dread  disease.  There 
are,  however,  frequent  exceptions  to  this  rule.  It  is  not  rare  for  patients 
to  lose  their  appetite  and  complain  of  lassitude,  chilliness,  headache, 
gastric  uneasiness,  etc.  These  symptoms,  when  they  occur,  are  com- 
monly noted  during  the  last  few  days  of  the  incubation  period. 
They  may,  however,  develop  as  early  as  a  week  before  the  invasive 
chill.  Now  and  then  a  patient  will  complain  of  slight  sore  throat 
during  the  last  days  of  this  stage. 

The  Stage  of  Invasion,  or  Initial  Stage. — This  stage  is  frequently 
ushered  in  with  suddenness  and  with  considerable  violence.  The 
earliest  symptom  is  most  frequently  a  chill.  This  may  be  severe  enough 
to  be  accompanied  by  chattering  of  the  teeth,  or  it  may  consist  of  a 
succession  of  creepy  sensations  scarcely  sufficient  to  attract  the  patient's 
attention.  Synchronously  with  the  chill  or  immediately  following  it 
the  fever  appears.  The  temperature  on  the  first  day  often  rises  to 
103°  or  104°  F.,  and  on  the  second  and  third  day,  with  perhaps  the 
exception  of  slight  morning  remissions,  it  rises  still  higher,  frequently 
reaching  105°,  and  in  some  cases  even  107°  F.  The  elevation  of 
temperature  is  usually  sudden;  in  but  few  diseases  does  it  rise  so  quickly 
from  the  normal  to  a  high  degree.     Even  in  varioloid  the  early  sjTiip- 


168  SMALLPOX 

toms  are  not  infrequently  equally  severe,  although  occasionally  they 
are  so  mild  as  to  escape  attention.  But  the  eruption  of  unmodified 
smallpox  seldom  if  ever  appears  without  being  preceded  by  a  well- 
marked  invasive  stage.  , 

During  the  continuance  of  the  fever  the  skin  is  hot  and  sometimes 
dry.  Profuse  sweating,  however,  is  by  no  means  uncommon;  this  is 
apt  to  come  on  in  the  evening. 

The  pulse,  as  a  rule,  is  full,  tense,  and  rapid,  its  frequency  generally 
corresponding  with  the  temperature  curve.  In  adults  it  varies  between 
100  and  130,  while  in  children  it  not  infrequently  reaches  160.  In  some 
cases  the  pulse  during  the  initial  stage  will  be  found  to  be  relatively  slow 
and  entirely  disproportionate  to  the  height  of  the  fever.  We  have  on  a 
number  of  occasions  noted  a  pulse  of  90,  80,  and  even  70,  with  a  tem- 
perature of  104°  or  105°  F.  These  cases  were  seen  in  the  hospital  on 
the  first  and  second  day  of  the  eruption ;  consequently  we  are  not  able 
to  state  whether  this  pulse  rate  was  present  at  the  onset  of  the  initial 
symptoms. 

The  respirations -are  almost  always  increased  in  frequency,  espe- 
cially when  the  temperature  is  excessively  high.  Prostration  is  often 
extreme,  being  out  of  all  proportion  to  the  length  of  the  illness.  Strong 
and  robust  patients  are  frequently  unable  to  stand  without  support,  and 
when  in  the  upright  position  soon  become  pale  and  liable  to  be  attacked 
by  vertigo  or  syncope.  Thirst  is  great,  the  lips  and  tongue  are  parched 
and  dry,  and  there  is  complete  loss  of  appetite. 

Constipation  is  a  common  symptom  and  is  apt  to  persist  throughout 
the  course  of  the  disease.  The  tongue  is  usually  coated  with  a  thick, 
yellowish  covering,  and  the  breath  is  heavy  and  offensive.  iVccording  to 
some  authors,  the  odor  from  the  body  of  a  patient  at  this  stage  of  the 
disease  is  so  peculiar  and  distinctive  as  to  make  it  possible  for  the  diag- 
nosis of  smallpox  to  be  made  by  this  symptom  alone.  We  must  confess 
that  our  olfactories  have  not  acquired  the  degree  of  acuteness  to  detect 
such  an  odor. 

Irritabihty  of  the  stomach  is  a  very  frequent  manifestation.  Occa- 
sionally the  first  symptom  noted  by  the  patient  is  severe  and  persistent 
vomiting.  In  such  cases  the  disease  has  on  more  than  one  occasion 
been  regarded  as  gastritis.  The  vomiting  often  continues  for  two  or 
three  days.  It  is  apt  to  be  accompanied  by  marked  tenderness  and 
pain  in  the  pit  of  the  stomach.  The  irritability  usually  ceases  when  the 
eruption  appears.  When  it  continues  longer  it  should  be  viewed  with 
some  soHcitude.  Especially  in  hemorrhagic  smallpox  is  this  symptom, 
together  with  epigastric  pain,  apt  to  be  distressing  and  prominent. 
Nausea  and  retching  are  present  in  some  cases  without  actual  emesis. 
_  Headache  is  the,moat.prominent-amongthe..early  nervous  symptoms. 
It  usually  follows  shortly  after  the  chill,  but  in  a  certain  proportion  of 
cases  it  precedes  it,  being  not  infrequently  the  earliest  evidence  of  ill- 
ness. Its  intensity  varies  greatly,  corresponding  in  a  measure  with  the 
height  of  the  febrile  action.  At  times  it  is  so  excruciating  as  to  cause 
even  self-restrained  individuals  to  cry  aloud.    The  face  is  often  flushed, 


77//';  S  YMPTOMA  TOIJX!  V  OF  SMA  L/J'OX  169 

the  carotids  visibly  pulsating.  Restlessness  and  sleeplessness  are  com- 
mon symptoms  diirino-  this  stage.  Children,  on  the  contrary,  are  some- 
times drowsy  and  sl('cj)y.  When  the  temj)erature  is  high,  delirium  is 
prone  to  supervene.  This  usually  takes  the  fonn  of  talkative  incoher- 
ence, although  some  patients  become!  (|uite  violent.  Coma  is  rare  in 
adults,  but  not  uncommon  in  children.  Convulsions  are  frequently 
seen  in  children,  more  so  ])erhaps  in  this  disease  than  in  any  other  of 
the  exanthemata.  They  may  be  severe  and  repeated,  and  may  contimie 
even  after  the  appearance  of  the  eruption. 

Pain  in  the  back  is  a  symptom  so  commonly  observed  that  it  is  believed 
to  be  of  special  diagnostic  value.  It  is  nol  ;is  (onstant  as  some  of  the 
otlier  symptoms,  yet  it  occurs  in  more  than  one-half  of  the  cases.  In 
perhaps  one-third  of  the  cases  it  is  sufficiently  severe  to  cause  the  patient 
to  volunteer  information  concerning  it.  Its  diagnostic  import,  therefore, 
is  due  rather  to  its  infrequency  in  the  other  acute  infectious  diseases 
than  to  its  constancy  in  smallpox.  The  lumbar  and  sacral  regions  are 
the  parts  to  which  the  pain  is  usually  referred,  although  it  may  extend 
to  the  dorsal  region.  As  a  rule,  it  is  more  severe  in  unmodified  sma]l})ox 
than  in  varioloid,  yet  this  rule  is  subject  to  many  exceptions.  In  hemor- 
rhagic  cas.e.s  the  pain  is  often  of  an  excruciating  violence.  Lumllaf  pain 
is  more  constantly  seen  among  female  than  male  patients,  owing  to  the 
fact  that  the  menstrual  function  is  very  liable  to  be  excited  by  the  initial 
illness  of  smallpox.  In  the  vast  majority  of  women  who  are  stricken 
with  smallpox  the  menses  appear  out  of  their  regular  period.  This  is  - 
true  of  mild  as  well  as  severe  cases.  The  premature  onset  of  the  men- 
strual flow  occurs  with  more  striking  frequency  in  this  disease  than  in 
any  other  of  the  infectious  maladies.  Pregnant  women  are  exceedingly 
liable  to  suffer  from  abortion  or  premature  delivery.  The  pain  in  the 
back  owing  to  these  causes  is  given  greater  .prominence  in  women- 

General  aches  and  pains  are  frequently  complained  of,  appearing  at 
the  same  time  as  the  headache  and  backache.  These  may  occur  any- 
where, but  are  usually  referred  to  the  lower  extremities,  particularly 
about  the  knees.  Thk-S-oreness  of  the  general  muscular  system  may 
Isaxi-to^  confusion  of  diagnosis  with  ia  griffe.  Veriigo,  which  is 
particularly  manifest  upon  the  patients  assuming  the  erect  position,  is 
a  common  early  symptom.  It  is  often  well  marked,  even  in  mild  cases, 
for  these  patients  are  more  apt  to  rise  from  their  beds.  Syncopal  attacks 
may  occur  in  weak  individuals. 

•"¥r©^iisseau  records  having  seen  during  the  initial  stage  patients  who 

suffered  from  temporary  loss  of  power  in  the  lower  extremities,  asso- 

x^olaiecl  in  a  few  instances  with  retention  of  urine.     When  this  condition 

occurs,  it  is,  in  our  experience,  most  likely  to  be  encountered  at  a  later 

period  of  the  disease. 

There  is  a  considerable  deg^ree  of  variation  in  the  character  and 
sequence  of  the  symptoms  constituting  the  initial  stage  of  smallpox. 
This  is  shown  in  the  following  analysis  of  ICO  cases  occurring 
in  the  epidemic  of  1901  and  1902:  The  patients,  who  were  taken 
without  selection,  were  closely  interrogated  as  to  the  nature  and  chrono- 


170  SMALLPOX 

logical  development  of  the  various  symptoms.  The  number  includes 
28  cases  of  confluent  smallpox,  15  with  very  profuse  and  semiconfluent 
eruptions,  29  with  eruptions  of  moderate  severity,  and  29  cases  of  mild 
varioloid.  Of  this  series  of  100  patients,  22  died.  Headache  was  the 
most  constant  of  the  initial  symptoms.  The  various  symptoms  men- 
tioned were  present  in  the  following  percentages:  Headache,  86  per 
cent.;  chills  or  chilKness,  78  per  cent.;  backache,  70  per  cent.;  vertigo, 
57  per  cent. ;  vomiting,  55  per  cent. ;  nausea  without  emesis,  10  per  cent. 
In  some  of  these  cases  the  symptoms  were  of  marked  severity,  while 
in  others  they  were  extremely  mild.  An  effort  was  made  to  determine 
the  earliest  symptom  observed  by  these  patients.  It  is  recognized  that 
some  inaccuracy  must  arise  from  an  attempt  to  chronologically  arrange 
the  symptoms  from  histories  thus  obtained. 


Chilliness  or  a  decided,  chill  was  the  first  symptom  in 
Headache  was  the  first  symptom  in        .       .       . 
Backache       ■<       "  "  "         .... 

Vomiting        "        "  "  "... 

General  aches  and  pains  were  the  first  symptoms  in 
Vertigo  was  the  first  symptom  in     . 


35  eases. 
26     " 
16     " 
9     " 

7      " 
2      " 


In  but  2  patients  out  of  the  100  was  Jhei;e.  complete  absence 
^f  initial  illness;  1  of  these  was  a  man,  aged  twenty-six  years,  witlfi 
a  very  mild  varioloid,  and  the  other  a  colored  woman,  aged  twenty- 
seven  years,  with  an  eruption  of  moderate  severity.  Upon  close  inquiry 
the  latter  patient  admitted  experiencing  fatigue  upon  the  day  preceding 
the  eruption.  It  is  possible  that  some  negative  histories  of  this  character 
may  be  due  to  poor  memory  or  lack  of  intelligence  on  the  part  of  the 
patients. 

In  the  severe  cases  the  initial  illness  was  always  well  marked,  although 
the  classic  symptoms  were  not  invariably  present.  A  man,  aged  fifty- 
five  years,  who  had  a  fatal  confluent  attack  had  merely  as  prodromes 
a  severe  chill,  fever,  and  prostration;  headache,  backache,  vertigo,  and 
vomiting  were  absent.  A  male  patient,  aged  twenty-nine  years,  with  an 
eruption  of  moderate  severity,  experienced,  during  the  initial  stage, 
fever,  repeated  vomiting,  and  pain  in  the  stomach,  without  any  other 
symptoms.  On  the  other  hand,  quite  a  number  of  patients  with  very 
mild  eruptions  gave  a  perfect  history  of  the  classic  initial  syndrome. 
A  young  woman  of  twenty  years,  for  instance,  with  only  three  or  four 
lesions  on  the  face  and  a  few  upon  the  arms  and  hands,  experienced, 
at  the  onset  of  the  disease,  headache,  backache,  repeated  vomiting, 
severe  chills,  vertigo,  and  aching  in  the  legs. 

These  observations  are  in  accord  with  those  of  most  writers,  and 
seem  to  illustrate  the  impossibility  of  forecasting  the  extent  of  the 
eruption  from  the  degree  of  severity  of  the  initial  symptoms.  We  have 
frequently  seen  the  most  aggravated  febrile  symptoms  followed  by  a 
"perfectly  insignificant  eruption.  Mild  initial  manifestations  are  rarely 
succeeded  by  a  severe  cutaneous  outbreak.  In  general  terms  it  may 
be  stated  that  severe  initial  symptoms  may  be  followed  either  by  a 
profuse  or  a  sparse  eruption,  and  that  mild  initial  symptoms  are  nearly 
always  followed  by  a  mild  eruption. 


THE  8  YMPTOMA  TO  L  0  d  V  0 F  SMA  fJJ'OX  17] 

The  urine,  in  the  initial  staf^e,  is  usually  more  or  lc.-,s  diuiinishcd 
aceordin*^  to  the  (le^rc(^  of  tlie  fever.  'J'Ik;  solid  constituents  are  nf>t  out 
of  their  normal  proportion,  excej)t  the  chlorides,  which  are  cc>nsiderahly 
diminished.  In  severe  cases,  especially  thos(;  about  to  hecrjuK;  hemor- 
rhafijic,  albuminuria  may  be  present.  A  high  gracJe  of  fever  might  be 
responsible  for  a  small  (juantity  of  albumin,  but  if  it  be  present  in 
great  abundance  a  malignant  type  of  the  disease  should  })e  suspected. 
Before  giving  an  unfavorable  prognosis,  however,  care  should  ])t  taken 
to  exclude  the  possibility  of  pre-existing  (Jisease  of  the  kidneys. 

The  spleen  may  be  found  enlarged  in  the  initial  stage  of  severe  small- 
pox.    In  mikl  cases  no  enlargement,  as  a  rule,  can  be  detected. 

I'eculiar  prodromal  rashes  often  make  their  appearance  during  the 
initial  illness.  When  they  develop  it  is  usually  j^ji^ori  .the  second  day  of 
.Jije  invasive  fever.  They  disappear  ordinarily  in  from  twenty-four  to 
forty-eight  hours.  They  may,  however,  continue  several  days  after  the 
"appearance  of  the  eruption.  The  frequency  of  these  rashes  appears  to 
vary  in  different  epidemics.  During  the  widespread  and  malignant 
epidemics  of  1871  and  1872  they  were  very  common.  Osier  noted  these 
rashes  during  this  period  in  13  per  cent,  of  his  cases.  These  eruptions 
are  not  so  apt  to  be  observed  in  smallpox  hospitals,  inasmuch  as  they 
disappear  commonly  before  the  diagnosis  is  made  and  the  patient 
conveyed  to  the  hospital.  The  most  common  type  is  that  resemhling 
measles,  with  which  disease,  indeed,  it  is  liable  to  be  confounded.  The 
eruption  has  an  irregular  distribution,  bei-ng  at  times  generalized  and 
at  other  times  limited  to  certain  regions  of  the  body.  It,  moreover, 
differs  from  the  eruption  of  measles  in  that  the  rash  is  not  elevated 
above  the  level  of  the  skin  and  therefore  scarcely  appreciable  to  the 
finger  when  passed  over  it.  Its  ephemeral  character  is  also  a  differ- 
entiating feature.  This  roseola  variolosa,  as  it  has  been  designated, 
has  a  close  analogue  in  the  roseola  vaccinosa  which  occasionally  appears 
about  the  ninth  to  the  eleventh  day  after  vaccination. 
— JThfi  jcarZajt74^z/orm  rash  is  less  common  than  the  measles-Hke  eruption. 
It  may  involve  a  large  part  of  the  cutaneous  surface,  but  is  more  apt 
to  affect  certain  areas,  as  the  thighs,  inguinal  regions,  extensor  surfaces 
of  the  extremities,  and  the  trunk.  Some  authors  refer  to  the  appearance 
of  an  urticarial  eruption  in  rare  cases. 

The  petechial  or  hemorrhagic  initial  rash  has  a  special  predilection 
for  certain  regions  of  the  body  which  were  carefully  studied  by  Simon, 
of  Hamburg.  This  writer  pointed  out  the  frequent  occurrence  of  the 
eruption  in  the  lower  abdominal,  inguinal,  and  genital  regions  and  inner 
aspects  of  the  thighs,  constituting  a  triangle  whose  base  traverses  the 
neighborhood  of  the  umbilicus  (the  so-called  crural  triangle  of 
Simon).  The  "  axillary  triangle,"  including  the  inner  aspect  of  the 
arm,  axilla,  and  pectoral  region  is  also  a  commonly  affected  area.  The 
petechial  rash  is  also  frequently  seen  along  the  lateral  surface  of  the 
thorax  and  abdomen.  The  eruption  consists  of  closely  aggregated, 
pinpoint  to  pinhead  sized,  purplish  or  clarety  spots,  which  are  in  such 
intimate  juxtaposition  as  to  convey  the  impression  of  a  diffuse  redness. 


172  SMALLPOX 

Being  the  result  of  a  hemorrhagic  extravasation  into  the  skin,  the 
discoloration  does  not  disappear  upon  pressure. 

Occasionally  an  erythematopetechial  rash  is  seen,  the  eruption 
partaking  of  the  characters  of  both  the  erythematous  and  hemorrhagic 
rashes. 

The  petechial  eruptions  may  occur  in  cases  which  later  .prove  to  be 
.  quite  mild.  More  often,  iioweyer,  they  arejhe  harbingers  of  severe 
smallpox  of  the-^hemoi'diagic  type.  The  morbijliform  eruptions  in"mlr~ 
experience  are  muchino-re  .common  -in,,,  cases  o|]jaHoloM7~aildTE(SF" 
"  Qccurreuce,  therefore,,  may  ♦be  regarded  as  an  auspicous  sign.  We  are 
able  to  recall  two  cases  of  smallpox  in  vaccinated  individuals  in  which 
the  roseolous  eruption  was  practically  the  only  cutaneous  manifestation. 
In  one  of  these  cases,  it  is  true,  about  half  a  dozen  small  variolous 
papules  appeared  as  the  initial  rash  faded  away,  but  they  disappeared 
in  two  or  three  days  without  becoming  in  the  slightest  degree  vesicular. 
'  These  cases  belong  to  the  class  commonly  designated  variola  sine 
exantkemate,  which  is  the  most  benignant  form  that  smallpox  may 
assume.  That  such  cases  are  occasionally  encountered  is  evident  from 
the  writings  of  both  ancient  and  modern  authors.  Perhaps  in  every 
epidemic  patients  are  seen  who  give  a  history  of  exposure  to  smallpox 
and  who,  in  due  course  of  time,  are  suddenly  seized  with  chills,  followed 
by  headache,  fever,  vomiting,  prostration,  and  pain  in  the  back.  These 
symptoras  continue  iox  three  or  four  days,  and.,iheik^;UJ3si4e~jftdth,0Lut. 
the  development  of  any  eruption  except  perhaps  one  of .lhe.4irQ.dromal 
^rashes  to  jvhich  reference  has  been  made.  It  is  impossible  to  explain 
such  cases  on  any  other  supposition  than  that  th^ disease-jy as.. ,  XMJQ^ 
without. the  eruption.  Trousseau  refers  to  cases  observed  by  him  in 
which  the  only  symptoms  characteristic  of  the  disease  were  a  "few 
pustules  on  the  pharynx  and  the  pendulous  veil  of  the  palate." 

It  may  be  of  interest  to  record  the  histories  of  two  patients  under 
our  observation  upon  whom  but  a  single  variolous  lesion  appeared: 

B.  H.,  aged  twenty-six  years,  suffering  from  measles,  was  sent  into  the 
Municipal  Hospital  under  the  erroneous  diagnosis  of  smallpox.  He 
was  immediately  vaccinated,  but  this  and  subsequent  attempts  failed. 
,^_^^,^  At  the  end  of  ten  days  he  was  seized  with  high  fever  (104°  F.),  headache, 
^/^  and  vomiting.  A  few  days  later^a  single  papulE  appeareiLin  JJie-rPight 
loin.  This  went  onT6""vesTcTe  formation,  becoming  characteristically 
iimbilicated,  but  dried  up  within  a  few  days.  The  patient  claimed  to 
have  had  smallpox  at  the  age  of  eight  years,  but  showed  merely  a  single 
pit  upon  the- face. 

The  following  case  presents  a  somewhat  similar  history: 

W.  G.,  a  colored  lad,  aged  fifteen  years,  was  vaccinated  four  years 
prior  to  admission;  he  presents  a  good  vaccination  cicatrix.  He  was 
brought  into  the  hospital  from  a  house  from  which  several  patients  with 
smallpox  were  removed.  On  admission  he  had  a  temperature  of  102° 
F.  and  presented  other  well-marked  initial  symptoms.  On  the  sub- 
sidence of  these  symptoms  he  developed  a  single  typical  papule  on  the 
trunk.  ^--^     "^ 


77/  /-;  S  YMI'TO  MA  TO  L  0  CI  Y  O  F  SMA  1, 1. 1 'OX  ]  7;j 

These  cases  come  almost  within  the  flefinition  of  viiriol.-i  wiMioul  an 
exaiithem.  If  smallpox  may  occur  with  tlic  a[)()Ciiruiic<'  of  hut  one 
lesion,  there  is  no  reason  why  it  should  not  at  times  rjevelop  witlifjut 
any  eni|)ti()n  whatsoever. 

The  duration  of  the  initial  stage  is  commonly  iorty-ei;i;lil  lo  seventy- 
two  hours;  it  is  rarely  less,  but  it  may  be  somewhat  prolonged.  Trousscair 
held  that  the  longer  the  ernj)tion  was  delayed  in  its  aj)j)earance,  tlu; 
more  favorable  was  the  prognosis.  This  is  scarcely  bf^rne  out  by  exyx-ri- 
ence.  It  is  misleading  to  draw  any  prognostic  conclusions  from  fli(; 
duration  of  this  stage. 

It  is  commonly  stated  in  text-books  that  u|)on  (lie  appearance  of  the 
eruption  of  smnllpox  the  fever  subsides  and  a  general  abatement  of 
the  systemic  symptoms  occurs.  In_our_^ejqp£nence  a  decided  rennssion 
in  the  temperature  does- not. take  place  in  unmodified  smallpox  until 
the  second,  third,  or  fourth  day  of  the  eruption.  In  very  mild  cases, 
"more  particularly  in  those  modified  by  previous  vaccination,  the  temper- 
"atui'e  may  fall  to  normal  as  the  exanthem  makes  its  appearance.  "\Vith 
tlTe  fall  of  the  fever  there  is  a  cessation  of  the  pains  and  a  general  improve- 
ment in  the  condition  of  the  patient.  In  mild  cases  of  varioloid  the 
illness  of  the  patient  is  terminated  at  this  stage.  In  severe  cases  the 
improvement  constitutes  but  a  brief  respite,  and  then  the  grim  struggle 
with  the  disease  begins. 

Stage  of  Eruption. ^ — By  carefully  observing  the  early  stage  of  the 
disease  it  will  be  found  that  the  true  erujDtion  makes  its  appearance  with 
remarkable  regularity  on  the  third  3ay  oi  the  illness,  calculating  from 
The  clay  on  which  the  initial  chill  or  rigor  occurred.  In  modified  smallpox 
deviations  from  this  rule  may  be  noted.  The  eruption  almost  always 
appears  first  on  the  forehead  and  temples  near  the  edge  of  the  hair, 
"ana  on  the  wrists.  Not  infrequently  it  is  seen  first  on  the  upper  lip 
SLiKTaround  the  mouth.  It  rapidly  spreads  to  the  scalp,  face,  neck,  ears, 
forearms,  and  hands,  always  showing  a  decided  preference  for  the 
cutaneous  surfaces  habitually  exposed  to  the  atmosphere.  In  the  course 
of  twenty-four  hours,  sometimes  somewhat  earlier,  it  extends  to  the 
body  and  lower  extremities.  It  does  not  simultaneouslv  afifect  these 
regions,  but  attacks  in  succession  the  back,  arms,  breast,  and  finally 
the  legs  and  feet.  In  rare  cases  the  exanthem  may  be  first  noted  on  the 
trunk  or  extremities. 

TheJ[i,ill  complement  of  lesions  does  not  make  its  appearance  at  once 
in_any  given  part;  the  eruption  continues  rather  to  multiply  for  two  or 
three  days  before  its  definite  limit  is  reached,  ^ii  varioloid^iiew  lesions 
,  may  continue  to  appear  for  a  longer  period  of  time.  I  pon  carefully 
examining  the  eruption  it  is  seen  that  many  lesions  develop  at  the  sites 
of  hair  follicles  or  orifices  of  the  sebaceous  and  sudorific  glands. 

The  eruption  begins  as  small  red  spots  or  >Ji£cidcs  some  of  which 
may  be  so  small  and  faint  as  to  be  scarcely  visible,  while  others  reach 
the  size  of  a  lentil-seed.  The  color  is  at  first  pinkish-red,  later  assuming 
a  deeper  tint.  In  many  cases  the  lesions  on  the  trunk  and  extremities 
present  the  appearance  of  flea-bites.     The  lesions  gradually  increase  in 


174  SMALLPOX 

size  and  number,  becoming  more  and  more  prominent,,  so  that  in  twenty^., 
_iau4?-]iQurs  they  assume  the  form  of  elevated  papules,  with  a  cEaracteristic 
feel.  The  early  papules,  particularly  about  the  forehead  and  cheeks, 
may  be  more  demonstrable  to  the  sense  of  touch  than  to  the  eye.  They 
possess  a  peculiar  induration,  and  convey  to  the  finger  a  sensation 
similar  to  that  which  would  be  produced  by  grains  of  shot  embedded 
in  the  skin.  The  "shotty"  feel  varies  in  degree  in  different  cases. 
Some  papules  are  extremely  hard,  while  others  possess  comparatively 
little  induration.  They  are  at  first  always  discrete,  but  they  may  rapidly 
increase  in  number  and  become  confluent,  even  before  the  vesicular 
stage  is  reached. 

On  the  third  day  of  the  eruption,  or  the  fifth  day  of  the  disease,  very 
many  of  the  lesions  which  made  their  appearance  first  will  be  found 
to  contain  a  little  clear  serum.  Indeed,  in  many  patients,  one  will  be 
able  to  note  on  the  second  day  a  lesion  here  and  there  which  has  become 
vesicular  in  advance  of  the  general  eruption.  These  precocious  vesicles 
are  frequently  of  diagnostic  import,  enabling  one  in  doubtful  cases  to 
assert  the  variolous  nature  of  the  disease.  By  the  fourth  or  fifth  day 
all  of  the  lesions  are  converted  into  vesicles.  At  this  stage  they  commonly' 
have  the  size  and  shape  of  a  split-pea.  Small  vesicles  are  apt  to  be 
conical  or  acuminate,  while  the  larger  lesions  have  a  convexly  flat  or 
hemispherical  appearance.  The  vesicle  of  smallpox  is  extremely  firm; 
not  infrequently  it  feels  harder  to  the  finger  than  the  papule  from  which 
it  developed.  In  no  other  disease  do  the  vesicles  acquire  such  a  degree 
of  induration  and  hardness.  The  color  of  the  vesicle  is  at  first  pinkish, 
the  tint  extending  to  the  areola  surrounding  it.  Later,  as  the  fluid 
exudation  into  it  increases,  it  assumes  a  peculiar  opaline  or  pearly  hue. 
This,  with  the  shining  and  glistening  surface,  imparts  to  the  vesicle  a 
most  distinctive  appearance.  One  of  the  most  characteristic  features 
of  the  smallpox  vesicle  is  the  so-called  "umbilication."  In  the  smaller 
acuminate  vesicles  this  is  seen  as  a  minute  central  depression  or  invagi- 
nation, representing  in  all  probability  the  mouth  of  a  hair  follicle  or 
sweat  duct.  This  form  of  umbilication  may  occasionally  be  met  with 
in  other  cutaneous  diseases,  when  the  lesions  are  situated  at  the  mouths 
of  the  pilary  or  sudoriparous  orifices.  In  the  larger,  pea-sized  vesicles 
the  umbilication  is  seen  as  a  round,  oval,  or  slightly  irregular  indentation. 
In  this  case  the  depression  is  flatter  and  is  probably  due  to  the  bulging 
of  the  periphery  of  the  pock.  This  latter  form  of  umbilication  is  of 
important  diagnostic  value,  as  but  few  other  vesicular  diseases  produce 
quite  the  same  appearance.  The  forearms  and  the  backs  of  the  hands 
are,  perhaps,  the  regions  upon  which  umbilication  is  most  character- 
istically seen.  Umbilication  is  only  observed  in  a  certain  proportion 
of  vesicles.  It  is  by  no  means  a  constant  feature  of  smallpox  eruption- 
and,  indeed,  is  not  infrequently  absent  altogether.  This  is  particu- 
larly true  of  cases  of  varioloid.  A^form  of  secondary  umbilication  is 
commonly  seen  during  the  stage  of-  decline  or  desiccation,  when  the 
pustules,  as  the  result  of  rupture  or  drying,  show  a  depression  in  the 
centre. 


Till':  S  YMI'TOMA  TOLOd  Y  OF  AM/.I  LLI'OX  175 

If  one  ()l),serv(^s  closely  ilic  lar/^c,  clear  vesicles  of  nlioiil  iIk-  fifili  or 
sixth  (lay,  j)ar<,iciiliirly  those;  situated  on  tiie  dorsal  surfaces  ot"  tin; 
hands,  one  can  fre(juently  discern  jliroii^di  (lie  epidermal  roof  srjrriefhing 
of  the  interior  construction  of  the  lesions.  'I'hey  will  \h',  seen  1o  he 
made  up  of  compartments  which  are  divided  by  vertical  septa,  very 
much  Hke  the  divisions  of  an  orange.  The  vertical  partitions  are 
formed  by  the  spiiniing  out  and  reticulation  of  the  epithelial  cells  f)f 
the  rete  mucosuin.  This  accounts  for  the  nudtilocular  chai'acter  of  the 
smallpox  vesicle,  and  explains  the  inability  to  completely  evacuate  its 
contents  by  a  single  puncture.  T^arge,  fully  developed  vesicles  frecjuently 
show  at  their  central  summit  a  disk  of  the  color  of  yellowish  serum, 
and  around  the  periphery  a  whitish,  puriform  ring  looking  not  unlike 
an  arcus  senilis. 

The  predominance  of  the  eruption  of  smallpox  on  the  face  and  term- 
inal extremities  is  to  be  accounted  for  by  the  greater  vascularity  of  the 
skin  in  these  regions.     That  lesions  are  attracted    by  an  overfilling  of 

Fig.  22 


Smallpox  eruption  showing  confluence  over  an  area  upon  which  iodine  had  been  applied  before 

the  eruption  appeared. 

the  cutaneous  vessels  is  seen  in  the  excessive  development  of  the  erup- 
tion wherever  the  skin  has  been  irritated  or  congested.  It  is  a  common  \ 
experience  in  the  hospital  to  see  in  a  discrete  case  of  smallpox  a  profusion 
of  lesions  over  a  rectangular  area  in  the  lumbar  or  epigastric  region 
where  a  mustard  plaster  had  been  applied  during  the  initial  stage  for 
the  relief  of  pain.  Fig.  22  shows  a  marked  confluence  of  the  pustules 
in  the  form  of  a  band  on  the  wrist  where  the  patient  had  applied  iodine 
for  a  sprain  received  before  his  illness.  An  intense  coalescence  of  the 
eruption  upon  the  forearm  is  seen  in  Fig.  23.  This  was  occasioned  by 
the  presence  of  a  sunburn  upon  these  parts. 

It  is  only  when  mechanical  or  chemical  irritation  is  applied  to  the 
skin  before  the  appearance  of  the  eruption  that  an  increase  in  the  num- 
ber of  lesions  is  produced.  We  have  frequently  applied  tincture  of 
iodine  and  similar  applications  to  the  skin  in  the  early  days  of  the  erup- 
tion without  augmenting  the  variolous  crop  in  the  region  thus  treated. 
Some  of    the  older  physicians  purposely   irritated  the  skin   of  certain 


176 


SMALLPOX 


portions  of  the  body  with  the  hope  of  deflecting  the  eruption  from  the 
face  to  the  regions  thus  treated.  Unfortunately,  the  eruption  was 
increased  in  the  manipulated  areas  without  diminishing  the  number  of 
lesions  on  the  face. 


Pig.  23 


Smallpox  eruption  showing  areas  of  extreme  confluence  which  had  been  the  seat  of  a  sunburn 
before  the  eruption  appeared. 


Stage  of  Suppuration. — The  contents  of  the  vesicles  gradually  become 
more  and  more  turbid,  as  the  result  of  the  increased  exudation  of 
leukocytes,  until  the  lesions  become  frankly  purulent.  This  condition 
is  usually  reached  in  unmodified  smallpox  about  ihe  .sixth  day  of  the 
eruption,  and  marks  the  beginning  of  the  stage  of  suJ3puration.  The 
pustules  now,  in  good  part,  become  large  and  globular,  and  stand  out 
prominently  from  the  skin.  Their  color  varies  somewhat  in  different 
cases.  At  times  the  pustules  acquire  a  distinctly  yellowish  tint  not 
unlike  the  color  of  ordinary  pus.  Frequently,  they  retain  until  ruptured 
a  peculiar  chalky  or  grayish-white  hue.  The  reddish  areola,  which  is 
observed  about  the  vesicles,  develops  in  this  stage  into  a  broader, 
deeper-hued,  violaceous  halo.  Where  the  lesions  are  closely  aggregated 
the  entire  interpustular  integument  becomes  reddened  and  tumefied. 


PLATE  XV. 


Well-pronouneed  Discrete  Smallpox  in  an  Unvaecinated. 
Subject  on  the  Eighth  Day  of  Eruption,  showing  the  relative 
sparsity  of  the  lesions  upon  the  trunk. 


THE  SYMI'TOMATOIJX;  Y  OF  SMAIJJ'OX 


177 


On  the  face  and  scalp,  where  the  eruption  is  apt  fo  be  profiis<;,  tlie 
redness  and  intninesc;enec  are  so  extreme  as  to  Hinder  tli(!  features  of 
the  [)atients  eoni[)letely  unrecogni/ahle.  The  eyeh'ds,  as  the  result  of 
oedema  of  the  loose  areolar  tissue,  l)ecome  enormously  f)uffed  and  com- 
pletely close  the  palpebral  cleft,  which  is  bathed  in  a  puriform  secretion. 
The  patient  for  a  time  is  unable  to  see,  owinj^  to  a  complete  closure  of 
the  eyelids.  The  lips,  nose,  and  ears  are  distorted,  the  normal  contour 
of  the  face  is  lost,  and  the  entire  head  swollen  beyond  human  [)ropor- 
tions.  The  patient  presents  a  most  revolting  and  loathsome  appear- 
ance. One  seeino;  the  disease  for  the  first  time  in  this  stage  is  apt  to  be 
appalled  by  the  horrible  spectacle.  The  patient  is  sorely  distressed  by 
the  inflammation  and  swelling  of  the  scalp,  inasmuch  as  contact  with 
the  pillow  is  a  source  of  unendurable  pain. 

Fig.  24 


Discrete  smallpox  eruption  on  tbe  ninth  day,  showing  marked  oedema  of  the  face, 
completely  closing  the  eyelids. 


As  the  eruption  on  the  body  and  lower  extremities  is  later  in  making 
its  appearance  than  that  on  the  face,  so  also  is  it  later  in  reaching  matur- 
ation. When  the  lesions  upon  the  face  have  become  vesicular,  it  will 
be  found  that  the  efflorescence  upon  the  trunk  and  extremities  is  still  in 
the  papular  stage.  In  like  manner  the  facial  lesions  will  have  advanced 
to  pustulation  by  the  time  that  the  eruption  on  the  body  has  become 
vesicular.  There  is  noticeable,  therefore,  this  regular  multiformity  in 
the  character  of  the  lesions  upon  the  different  portions  of  the  body. 
About  the  eighth  day  the  pustules  on  the  face  have  reached  their 
greatest  (levelopmcMit,  and  the  process  of  retrogression  then  begins. 
They  become  yellowish,  present  a  shrunken  or  shrivelled  appearance, 
and  rupture  or  collapse.  On  rupturing  the  pustules  give  exit  to  a  viscid, 
glairy,  dirty-yellow  pus,  which  dries  in  the  form  of  yello^\"ish  or  brownish 
crusts.  A  gradual  subsidence  in  the  inflammation  and  swelling  takes 
place,  and  the  normal  outhnes  of  the  face  are  once  more  restored. 

12 


178 


SMALLPOX 


During  the  stage  of  pustulation  the  lesions  which  exhibited  umbili- 
cation  become  distended  and  globular,  thus  effacing  the  central  depres- 
sion. The  epithelial  bands  holding  down  the  centre  of  the  lesion,  in  all 
probability  become  dissolved  away,  permitting  the  roof  of  the  pustule 
to  assume  an  hemispherical  form. 

The  eruption  on  the,,trwn4^is-atoee*~a4^way«m-U,ch  les 
jon  other  parts  of  the  body^,^  Not  m|rgqjufijattyjjbe.i^^^  quite 

Jree  from  pustules,  even  wheii^ffiemce  and  hands  show  a  marked  degree 
of  confluence.  Exceptions  to  this  rule  are,  however,  occasionally  met 
with.  We  have  seen  patients  the  skin  of  whose  body  was  so  profusely 
covered  that  it  would  have  been  impossible  to  place  the  tip  of  the  finger 

Fig.  25 


Large,  full  pustules  on  the  seventh  day  of  the  eruption. 

upon  a  healthy  area  of  skin.  Of  course,  in  such  cases  the  danger  to 
the  patient  is  correspondingly  increased,  inasmuch  as  the  gravity  of  the 
disease  is,  as  a  rule,  directly  proportionate  to  the  extent  of  the  eruption. 

In  a  well-pronounced  case  of  semiconfluent  smallpox  under  our  care 
an  approximate  count  of  the  number  of  lesions  was  made.  This  was 
accomplished  by  dividing  the  cutaneous  surface  into  certain  areas  by 
means  of  a  colored  crayon  and  counting  the  pustules  within  these  bound- 
aries. Upon  the  face  and  scalp  the  confluence  of  the  pustules  precluded 
the  possibility  of  their  being  counted.  A  conservative  estimate  of  the 
number  present  was  therefore  made. 

The  number  of  lesions  computed  upon  the  different  portions  of  the 
body  is  herewith  appended: 


77//';  S  YM/'TOMA  TOIJXl  Y  OF  SMA  LLI'OX  179 


Total  oil  (IngerH  of  one  hand    • 


'I'hiiinb  ()1  I 

Index  finger  '.)! 

Middle    "       05  r  ...        392 

Ring        "       81  I 


llorsfil  .surl'uce  of  one  hand 3H2 

Palmar      "  "  " 129 

Total  lesions  on  both  hands  . I,Wk; 

PorearniR ■i,W) 

Anns 2,8io 

Chest 1.000 

Abdomen 17.5 

Thighs 4,180 

Legs 2,8.')0 

Feet 7.50 

Back 5,700 

Estimated  number  on  face  and  scalp 3,000 

Total 20,701 

By  evacuating  some  of  the  pustules  with  a  pipette  we  estimated  that 
the  lesions  at  the  height  of  their  development  each  contained  about 
three  drops  of  pus.  Such  a  computation  developed  the  surprising  fact 
that  the  patient  referred  to  carried  in  his  skin  about  five  quarts  of  pus. 

We  have  seen  large  men  with  more  profuse  eruptions,  who  must 
have  had  in  the  neighborhood  of  forty  thousand  pustules.  With  this 
prodigious  amount  of  purulent  material  in  the  skin  the  wonder  is  that 
any  patient  thus  afflicted  should  recover. 

'J^^llfL-pustulcs  on  the  trunk  appear  to  have  a  more  superficial  seat  in  . 
JJieL,akm  than  on  cutaneous  -surfaces  constantly  exposed  to  the  air;  hence,, 
ijtiiey  arc  not  accompanied  by  the  same  amount  of  inflammatory  swell- 
ing ov  ulcerative  destruction  of  the  cutis. _    There_  is,  _inQreover,  vei 
iitlle  tendency  on  the  trunk  and  lower  extremities  to  confluence  of~lEe~ 
lesions.    We  frequently  note  a  coalescence  of  two  or  three  pustules  as  a 
result  of  their  contiguity,  but  the  vast  majority  of  the  lesions  remain 
discrete. 

This  statement,  however,  does  not  apply  to  the  efflorescence  on  the 
hands  and.  feet.  In  these  regions  the  degree  of  confluence  may  be  intense 
and  cause  the  patient  great  suffering.  As  a  result  of  the  thickness  of" 
the  overlying  epidermis  on  the  palms  and  soles,  the  pustules  do  not  acquire 
as  great  a  prominence  as  elsewhere.  Being  bound  down  by  the  tense 
and  unyielding  horny  layer  of  skin,  pressure  is  made  upon  the  dehcate 
underlying  cutaneous  nerves,  producing  distressing  pain.  In  a  severe 
attack  of  smallpox  the  palms  and  soles,  the  fingers  and  toes,  and  the 
dorsal  surfaces  of  the  hands  and  feet  are  profusely  covered.  "\Mien  the 
pustular  stage  is  reached  the  patient  becomes  perfectly  helpless;  he  is 
unable  to  feed  himself  or  in  any  way  utihze  his  hands.  It  is  pitiful  to 
behold  him  in  bed,  with  his  hands  and  fingers  semiflexed,  and  his  arms 
•  outstretched  for  fear  of  the  dreaded  contact  with  the  bed-clothing.  At 
times  the  pustules  on  the  back  of  the  hands  fuse  and  produce  large 
bulla?,  or  even  an  extensive  undermining  of  the  epidermis  similar  to 
that  seen  in  a  bad  scald. 

During  the  suppurative  stage  a  most  penetrating  and  offensive  odor 


180 


SMALLPOX 


emanates  from  the  body  of  the  patient,  and  from  the  pus-stained  bed 
and  body  hnen.  This  stench  results  from  the  decomposition  of  the 
effete  and  purulent  discharge,  and  is  not  peculiar  to  smallpox.  In 
neglected  cases  the  odor  is  most  sickening,  and  may  pervade  the  atmos- 
phere of  a  room  or,  indeed,  of  an  entire  house. 

Eruption  upon  the  Mucous  Membranes.— Simuhaneous  with  the 
appearance  of  the  smallpox  efflorescence  upon  the  cutaneous  surface, 
or  a  little  earlier,  the  eruption  develops  upon  the  adjacent  mucous 
membranes.  The  involvement  is  almost  exclusively  confined  to  those 
mucous  surfaces  which  are  near  the  external  orifices,  or  to  which 
the    air   has    access.      The   eruption   early  attacks  the   lining  of   the 


Fig.  26 


Well-pronounced  smallpox  on  the  eighth  day,  occurring  during  a  particularly  mild 
epidemic,  the  lesions  being  very  superficial. 


mouth,  nose,  and  pharynx,  and  in  severe  cases  the  larynx,  bronchi, 
and  oesophagus.  The  extent  of  the  enanthem  bears  a  direct  relation  to 
the  severity  of  the  eruption  of  the  skin.  The  lesions,  however,  are 
seldom  as  profuse  upon  the  mucous  surfaces  as  upon  the  integument. 
If  an  examination  of  the  mouth  and  fauces  be  made  at  the  very  begin- 
ning of  the  eruptive  stage,  small  yet  distinct  red  spots  may  be  seen  upon 
the  roof  of  the  mouth,  buccal  surfaces,  and  anterior  arches  of  the  palate. 
These  macules  are  pinhead  sized  and  larger,  and  of  an  intense  red 
color,  which  contrasts  with  the  violaceous  or  bluish-red  tint  of  the  sur- 
rounding mucous  membrane.  In  a  short  time  the  spots  become  slightly 
elevated  or  papular,  frequently  exhibiting  a  whitish,  glistening  centre. 
The  parallelism  with  the  evolution  of  the  cutaneous  pock  ceases  at  this 


THE  S  YMI'TOMA  TO  LOG  Y  OF  SMA  /.  LI'OX  \  8  ] 

stage  of  the  (l('V('l()[)?iicii(.  Ttic  riiucous-rnenihr;iiie  lesion  (l(;c.s  not  pass 
tlu'ongh  llic  stage  of  j)aj)iile,  vesicle,  ainl  pustule,  l)iit  pursues  a  eliarae- 
teristic  eoiirst;  wliicli  is  detennined  \)y  its  j)eeuliar  structure  and  its  dif- 
ferent environment.  I'here  is  perhaps  an  effort  on  the  part  of  nature 
toward  the  formation  of  vesicles,  but  the  thin  and  delicate  e[>ithelium 
which  serves  as  a  covering  is  destroyed  by  the  macerating  influence 
of  the  moist  secretion  in  which  they  are  constantly  bathed.  As  the 
eruption  upon  the  skin  becomes  vesicular  and  j)ustular,  the  lesions  in  the 
mouth  assume  a  whitish  or  grayish  appearance,  with  but  little  if  any 
elevation  above  the  surface.  'Vhv  denudation  of  the  ey)itheHfd  r-ovcring 
of  the  pocks  leads  to  the  j)ro(lu('ti()n  of  circumscribed  cios  oii^  or  super- 
ficial ulcerations. 

'~'^^^^txricii'ii  of  Ike  /Aroa/,  particularly  on  swallowing,  is  one  of  the  most 
distressing  symptoms  of  the  early  eruptive  stage.  But  few  patients 
with  well-marked  attacks  escape  this  suffering.  Even  when  the  patient 
is  feeling  otherwise  well  the  condition  of  the  throat  constitutes  a  source 
of  bitter  complaint.  In  severe  cases,  at  a  later  stage,  the  mucous  mem- 
brane of  the  mouth  is  so  abraded,  swollen,  and  painful  that  the  use  of 
solid  food  is  rendered  impossible,  and  the  patient  is  forced  to  subsist 
entirely  on  a  liquid  diet. 

►XJae  tongue  is  often  the  seat  of  lesions  which  seriously  embarrass 
its  movement  in  speaking  and  eating.  Occasionally  an  intense  form 
of  glossitis  is  set  up,  causing  the  organ  to  swell  so  enormously  as  to  pre- 
vent its  retention  wholly  within  the  mouth.  This  condition,  which  was 
designated  by  the  older  writers  as  glossitis  variolosa,  is  apt  to  greatly 
interfere  with  swr.llowing,  and  is  under  all  circumstances  to  be  regarded 
as  an  unfavorable  sign. 

Much  annoyance  is  occasioned  by  the  presence  of  the  eruption  in  the 
nasal  cavities.  The  mucous  membrane  is  at  first  swollen  and  inflamed, 
and  later  covered  with  crusts  which  obstruct  the  nares  and  render  nasal 
breathing  difficult  and  often  impossible.  This  is  particularly  a  source 
of  distress  to  nursing  infants,  who  are  obliged  to  release  the  nipple  from 
time  to  time  to  obtain  the  necessary  amount  of  air. 

The  eruptive  process  may  involve  both  the  pharynx  ancl  l9,r^ix  and 
cause  so  much  inflammation  and  swelling  as  to  make  deglutition  difficult 
or  impossible,  or  it  may  lead  to  the  production  of  hoarseness  and  complete 
jiutb-Onia.  In  severe  cases  an  acute  oedema  of  the  glottis  may  develop, 
which  may  seriously  or  even  fatally  impede  respiration.  Trousseau  re- 
cords several  fatal  cases  of  this  character:  "  Three  smallpox  patients,  on 
the  eighth  day  of  the  disease,  which  had  run  a  perfectly  normal  course, 
were  suddenly  seized  with  a  fit  of  suffocation  which  carried  them  ofl'  in 
a  few  seconds,  before  there  was  time  for  anyone  to  come  to  their  assist- 
ance. In  one  patient  autopsy  showed  laryngitis,  with  variolous  lesions 
below  the  glottis." 

In  severe  smallpox  in  children  we  have  found  it  necessary  in  four 
instances  to  employ  intubation  in  order  to  prevent  asphyxia.  In  all  of 
these  cases  there  was  laryngitis  with  considerable  swelling  of  the  mucous 
membrane.    Although  relief  was  temporarily  alYorded,  death  ultimately 


182  SMALLPOX 

occurred  in  all  four  cases.  In  one  of  the  children  the  laryngeal  stenosis 
came  on  late  after  complete  decrustation  had  occurred  on  the  skin, 
and  at  a  time  when  the  child  appeared  to  be  on  the  road  to  recovery. 

The  mucous  membranes  of  the  lower  portion  of  the  body  may  also 
be  involved.  The  eruption  may  attack  the  vulva  and  the  mucous  sur- 
faces of  the  vagina,  but  the  lesions  in  these  parts  are  not  apt  to  be  abun- 
dant. The  lower  part  of  the  rectal  mucosa  may  also  be  the  seat  of  the 
variolous  eruption.  The  meatus  urinarius  is  occasionally  involved  in 
both  males  and  females,  but  the  urethral  channel  nearly  always  escapes. 

Delirium. — As  previously  stated,  a  variable  degree  of  delirium  may 
accompany  the  high  fever  of  the  initial  stage.  In  our  experience  the 
most  violent  disturbance  of  cerebration  occurs  during  the  early  eruptive 
period.  This  may  be,  in  some  cases,  merely  the  continuation  of  the 
earlier  delirium,  but  in  others  it  seems  to  begin  after  the  exanthem  has 
made  its  appearance.  Some  patients  are  apparently  the  subjects  of 
delusions  of  persecution  and  of  hallucinations,  and  imagine  that  some 
one  is  about  to  do  them  bodily  harm.  Acting  on  this  supposition  the 
demented  patient  attempts  to  escape  from  the  hospital  and,  what  is 
quite  strange,  will  almost  always  prefer  to  gain  egress  through  the 
window.  On  a  number  of  occasions  patients,  by  the  exercise  of  cun- 
ning and  the  awaiting  of  a  favorable  opportunity,  have  effected  their 
flight  with  marvellous  celerity,  and  have  gained  a  temporary  liberty 
in  this  manner.  In  some  patients  the  temporary  derangement  takes 
the  form  of  a  suicidal  or  homicidal  mania.  One  of  our  patients  at- 
tempted self-destruction  by  striking  himself  on  the  head  with  a  drinking 
mug,  inflicting  several  large  and  painful  wounds. 

On  another  occasion  a  female,  by  cunningly  embracing  an  opportune 
moment,  quickly  ran  to  an  open  fire-grate,  on  which  she  seated  herself. 
While  her  clothing  was  burning  around  her  and  her  flesh  charring,  she 
violently  resisted  the  efforts  of  the  nurse  to  extricate  her.  We  recall 
another  patient  who  rose  from  his  bed  at  night,  struck  the  nurse  to 
the  floor,  and  effected  his  escape  in  his  night-clothes;  he  wandered  a 
considerable  distance  from  the  hospital,  and  succeeded,  by  a  shrewd 
and  plausible  story,  in  prevailing  upon  the  credulity  of  a  wagon  driver, 
who  conveyed  him  to  his  desired  destination. 

These  patients  are  often  able  to  answer  questions  coherently,  and  one, 
unprepared,  may  be  completely  deceived  as  to  their  mental  condition. 
They  are  apt  to  exhibit,  however,  some  injection  of  the  conjunctivae 
and  a  wild  expression  of  the  countenance.  This  form  of  delirium  was 
called  by  the  older  writers  delirium  ferox. 

Patients  thus  affected  require  to  be  closely  watched,  and,  if  neces- 
sary, restrained  in  bed  by  straps  or  other  means.  When  a  patient  com- 
plains of  persecution  or  asks  to  be  permitted  to  attend  to  some  business 
at  home  for  a  day  or  two,  close  surveillance  is  necessary. 
•"^-We^have  observed  this  .active  delirium  most_pJ[ten_d^ 
and  vesicular  stag-e  of  the  eruption.  When  it  occurs  it  is  usually  asso- 
ciated  with  the  confluent  variety  of  smallpox,  yet  we  have  known  it  to 
occur  in  comparatively  mild  forms  of  the  disease  or  when  the  patient 


77//';  S  VM/'TOMA  TOLOd  Y  OF  SMA  IJJ'OX  1  8.*} 

had  become  (|uite  a})yr(!l,ic;.    The  persistence  of  (lie  (Iciiiiiiin  for  ,'i  niimlxT 
of  days  is  a  symptom  of  evil  portent. 

The  delirium  which  is  seen  later,  during  tlie  (jcclinc  of  iIk;  cruplifjii, 
is'oTa  d'iff(ifCTt"Char?iLf't;CT.    Tt  is  "then  of  a  low,  nmllcriii^  form,  and  fre- 

■  quen'fTy^ssocTated  with  general  tremor,  dry  t(jiigii(;,  quick  and  tremu- 
lous pulse,  and  a  collapsed  appearance  of  the  features.  These  nervous 
symptoms  are  not  ])eculiar  to  smallpox,  hut  may  be  seen  in  the  terminal 
stage  of  typhoid  and  other  fevers. 

The  various  forms  of  delirium,  while  more  frequently  observed  in 
alcoholics,  appear  to  be  the  result  of  the  poison  of  the  disease  acting 
upon  the  nerve  centres. 

It  has  already  been  stated  that  the  jjj^i^yL^^y^  in  unmodified  small- 

^QiX^acmti nues> high  until  the  third  or  fourth  day  of  the  eruption,  when 
there  occurs  either  a  well-marked  remission  or  a  brief  period  of  apy- 
rexia.  In  very  mild  cases  the  fever  subsides  earlier.  The  fall  of  the 
temperature,  at  this  stage,  even  in  severe  cases,  is  not  infrequently  very 
rapid,  so  rapid,  indeed,  as  to  drop  from  a  high  degree  to  normal  or  even 
subnormal  in  the  course  of  twelve  or  eighteen  hours.  The  difference 
between  the  morning  and  evening  temperature  is  not  great,  although 
the  latter,  as  a  rule,  is  slightly  higher.  When  the  temperature  falls 
there  is  usually  amelioration  of  all  the  symptoms.  The  pulse  becomes 
almost  normal;  the  respirations  are  easier;  the  pain  in  the  back,  head- 
ache, and  irritability  of  the  stomach  all  disappear,  except  in  critical 
cases;  the  delirium  ceases,  enabling  the  patient  to  rest  and  enjoy  re- 
freshing slumber.  Even  the  appetite  may  return,  and  tlie  patient  may 
be  led  to  believe  that  the  critical  period  of  the  disease  has  passed  and 
that  recovery  has  begun.  The  subsidence  of  the  symptoms  is  never  so 
complete  in  variola  vera  as  it  is  in  varioloid.  In  the  latter  variety  the 
fever  and  other  systemic  symptoms  frequently  disappear,  and  the  begin- 
ning of  convalescence  is  established;  but  in  the  former  the  chief  danger 
is  yet  to  be  encountered. 

At  or  sliortly  after  the  cornmencemeut  of  the  stage  of  suppuration 
tTie  ten\peratin-e  again  begins  to  rise,  and  continues  elevated  until  the 
completion  of  the  eruptive  process,  or  longer  if  complications  arise. 
This  rise  constitutes  the  so-called  secondary  or  suppurative  fever  of 
smallpox.  This  latter  .pyrexiaas, not  apt  to  equal  in. intensity  the  initial 
elevation  of  temperature.     When  the  disease  is  of  moderate  severity 

""^le^temperature  may  not  rise  above  102°  F.  or  103°  F.,  but  in  well- 
marked  confluent  cases  it  frequently  reaches  104°  F.,  rarely  exceeding 
that  point.  When  hyperpyrexia  develops,  the  thermometer  registering 
105°  F.,  106°  F.,  or  107°  F.,  the  danger  of  a  fatal  outcome  is  corres- 
pondingly increased.  The  maximum  degree  of  fever  is  often  reached 
during  the  hours  which  immediately  precede  dissolution.  Wunderlich 
reports  an  antemortem  temperature  of  109.2°  F.,  and  Simon  has  seen 
temperatures  of  110°  and  112°  F.  immediately  after  death, 
jrke  secondary  fever  commences  ordinarily  on  the.  fifth  or.  sixth  dajx^, 

,,,^the  eruption,  when  the  vesicles  begin  to  fill  with  .pus..  It  is  of  indefi- 
nite duration,  depending  directly  upon  the  extent  and  severity  of  the 


184 


SMALLPOX 


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THE  SYMPTOMA TO/.Od  Y  OF  SMA  IJJ'OX  1  85 

cutaneous  oulhrcak.  In  a  well-marked,  discrete,  or  semiconflueiit 
,sTnall])()x  the  pyrexia  is  apt  to  last  froui  three  to  six  days.  In  severe  con- 
(liicut  cases  it  may  continue  for  eif^ht  to  tw(;lve  days  or  IfMi^er.  It  is 
not  uncommon  U)Y  the  secondary  fever  to  nier<i;e  wifhont  interrrn'ssion 
into  the  pyrexia  produced  by  the  common  septic  complications,  such 
as  boils,  abscesses,  etc.  The  elevation  of  temperature  may,  under  such 
conditions,  continue  for  four,  five,  or  six  weeks  or  even  longer.  In  the 
befi;innin(ij  of  the  snpj)urative  fever  the  variation  between  the  morning 
and  eveninf>;  tcmj)crature  is  apt  to  e(|ual  one  or  two  dcffrees.  The  max- 
imal elevation  usually  occurs,  in  severe  cases,  between  the  seventh  and 
tenth  days.  I^ater,  when  boils  and  abscesses  develop,  the  diurnal 
variations  are  most  pronounced,  the  evenin<^  fever  not  infrefjuently 
reaching  104°  or  105°  F.,  while  the  matinal  temperature  registers  only 
99°  F.  The  pulse  and  respiration  correspond  in  a  general  way  with  the 
temperature  curve.  The  pulse,  however,  is  apt  to  be  higher  in  propor- 
tion to  the  temperature  than  during  the  initial  stage.  With  a  tempera- 
ture of  104°  or  105°  the  cardiac  pulsations  not  infrecjuently  reach  140 
or  150  to  the  minute.  When  the  morning  remission  occurs  there  is  a 
considerable  slowing  in  the  pulse  rate.  As  is  quite  to  be  expected,  the 
patient  experiences  more  comfort  in  the  mornings  than  later  in  the  day. 
During  the  pustular  stage  the  chief  complaint  of  the  patient  is  the  gen- 
eral soreness  of  the  skin.  The  couch  upon  which  he  lies  is  metaphor- 
ically, if  not  actually,  "a  bed  of  thorns;"  whichever  way  he  turns  he 
makes  pressure  upon  the  sensitive  and  inflamed  pocks.  Nervous  appre- 
hension, restlessness,  and  sleeplessness  are  prominent  symptoms  of 
this  period.  The  patient  is  conscious  of  an  increasing  degree  of  pros- 
tration, and  is  frequently  much  concerned  as  to  the  outcome  of  the 
illness.  It  becomes  necessary  to  allay  the  nervousness  of  the  patient 
and  induce  sleep  by  the  administration  of  an  anodyne.  At  the  end  of  the 
eighth  or  ninth  day  a  sudden  improvement  in  the  general  condition  of 
the  patient  is  often  observed.  The  sufferer  becomes  brighter,  volunteers 
information  that  he  feels  better,  and  exhibits  altoo;ether  a  lesser  dejjree 
of  prostration.  This  is  usually  coincident  with  the  onset  of  the  period 
of  involution  and  retrogression  of  the  eruption. 

Period  of  Involution  and  Retrogression  of  the  Eruption. — The 
exanthem  of  smallpox  reaches  the  acme  of  its  development  with  the  com- 
pletion of  the  pustular  stage.  This  constitutes  the  turning  point  not 
only  of  the  eruption,  but  frequently  of  the  disease.  The  first  evidence 
of  retrogression  of  the  exanthem  is  noted  in  the  subsidence  of  the 
inflammatory  swelling  of  the  skin,  more  particidarly  in  the  immediate 
neighborhood  of  the  pustules.  The  abatement  is  first  seen  on  the  face, 
where  the  redness  and  oedema  have  been  most  conspicuous.  The  eye- 
lids become  less  swollen,  permitting  the  patient  to  again  perceive  the 
grateful  light  of  day.  The  tumefied  features  gradually  assume  their 
normal  contour,  and  the  patient  begins  to  acquire  some  semblance  of  his 
former  self.  Synchronous  with  the  disappearance  of  the  intumescence 
the  pustules  begin  to  dry;  this  period  is  called,  therefore,  the  stage  of  desic- 
cation.   The  drying  of  the  contents  of  the  pustule  is  soon  followed  by 


186  SMALLPOX 

a  casting  off  of  the  crusts,  when  the  stage  of  decrustation  is  entered  upon. 
Nature  in  this  manner  attempts  to  rid  the  surface  of  the  skin  of  the 
effete  products  which  have  there  collected,  and,  finally,  restore  it  to  its 
normal  condition. 

The  involution  of  the  smallpox  exanthem  does  not  occur  simulta- 
neously upon  all  portions  of  the  body  surface,  but  follows  the  same 
sequence  observed  during  the  development  of  the  eruption.  It  is  but 
natural,  therefore,  that  the  first  evidence  of  desiccation  should  be  found 
in  the  facial  lesions.  The  pustules  in  this  region  may  dry  without  rup- 
ture, although  more  commonly  the  purulent  contents  of  the  lesions 
exude  upon  the  surface  and  dry  in  the  form  of  yellowish  crusts.  This  color 
gradually  becomes  darker  until  it  assumes  a  brownish  tint.  In  neglected 
cases  the  crusts  may  become  almost  black,  enveloping  the  face  in  an 
unsightly,  immovable  mask.     The  adherence  of  the  crusts  to  the  subja- 


Unusually  large  and  confluent  pustules  on  the  ninth  day  of  the  eruption. 

cent  tissues  varies  in  degree  according  to  the  depth  and  intensity  of  the 
involvement  of  the  cutis.  Where  the  pustule  is  superficially  seated 
and  there  is  no  ulceration  of  the  skin,  the  crust  is  readily  detached, 
exposing  to  view  merely  a  reddened  area  of  the  skin. 

At  the  same  time  that  desiccation  is  well  established  on  the  face,  the 
trunk  and  extremities  will  exhibit  lesions  distended  with  fluid  pus. 
These  rupture,  form  crusts,  and  then  pass  through  the  process  just 
described.  At  this  period  of  the  disease  the  offensive  odor  previously 
mentioned  becomes  most  marked;  in  some  cases  it  is  quite  unbearable, 
especially  when  the  contents  of  the  pustules  discharge  and  decompose  on 
the  skin,  or  soak  into  the  bed-clothes  and  there  undergo  putrefaction. 

After  the  rupture  of  large  pustules  the  centres  frequently  dry  and 
sink  in,  producing  a  cup-shaped  depression  or  umbilication.  This 
secondary  umbilication  differs  from  the  primary  variety  in  being  dis- 
tinctly larger,  more  conspicuous,  and  occurring  at  a  much  later  stage 
of  the  eruption.  This  form  of  umbilication  is  most  typically  seen  on 
the  dorsal  surfaces  of  the  hands. 


THE  SVMPTOMA  TOLOd  Y  OF  SMA  IJjPOX 


180 


of  the  skin  and  mucous  inciiihranes  the  temperature  falls  less  rapidly, 
or  if  complications  arise  it  continues  for  a  varying  period  according  io 
the  nature  of  the  associated  conditions.  Although  the;  f(!ver  is  stearjily 
<lecrcasin<i;,  the  piitient  is  still  in  danger  from  exhausliori,  for  the  hearf, 
kidneys,  and  other  organs  hav(;  heen  severely  taxed  hy  the  septicrernic 
poisoning. 

The  mucons-meml)rane  lesions  of  the  upper  air  passages  improve  in 
favorable  cases  at  a  rather  earlier  period  than  the  cutaneous  manifes- 
tations, l^he  distressing  ])a-in  on  swallowing  has  often  disar)j)eared  by 
the  sixth  day.  The  nasal,  buccal,  and  pharyngeal  eruption,  being  less 
deep  and  destructive,  undergoes  a  comparatively  rapid  involution. 
In  regular  cases  of  variola  vera  it  usually  rc(juires,  after  desif;cation 
_  has  c.oumieuced,  from  three  to  four  weeks  for  all  of  ihe  crusts  to  become 
detached  and  fall  off.  This  makes  the  entire  duration  of  the  disease 
a^otrt~five  61-  six  weeks. '  "^^ 

Fig.  .32 


Well-pronounced  discrete  smallpox  ;  clustering  of  lesions  due  to  previous  abrasions 

at  such  sites. 

During  the  drying  stage  a  new  symptom  is  added  to  the  sufferer's 
already  extensive  category  of  ills.  The  incrustation  of  the  pustules  is 
accompanied  by  the  development  of  itching  which  varies  in  intensity 
from  slight  annoyance  to  unendurable  distress.  Adults  are  usually 
enabled  to  restrain  themselves  from  scratching  by  the  exercise  of  self- 
control.  Children,  on  the  other  hand,  yield  to  the  impulse  to  purchase 
relief  by  scratching  or  rubbing,  with  the  result  that  injury  is  often 
inflicted  upon  the  skin.  It  is  not  uncommon  to  see  in  children,  who 
have  had  unbridled  license  in  the  use  of  their  hands,  large,  abraded, 
bleeding  surfaces  or  crusted  sores  where  the  pustules  have  been  gouged 
with  the  finger-nails.  It  is  popularly  believed  that  the  scarring  in 
smallpox  is  due  to  secondary  injury  from  scratching.  ^Miile  this  agency 
may  be  a  factor  in  the  production  of  a  few  of  the  cicatrices,  the  vast 


190  SMALLPOX     . 

majority  of  them  result  from  the  destruction  of  portions  of  the  corium 
by  the  variolous  inflammation.  That  finger  traumatism  plays  but  an 
inconsiderable  role  in  the  scarring  is  evidenced  by  the  fact  that  children, 
despite  the  mechanical  violence  which  they  inflict  upon  the  skin,  escape 
as  a  rule  with  less  disfigurement  than  adults.  This  is  doubtless  due  to 
the  fact  that  the  pocks  in  children  are  more  superficially  situated  in  the 
integument.  The  most  serious  consequence  of  scratching  is  in  the 
increased  liability  to  pyogenic  infections  of  the  skin  and  the  subcutaneous 
tissue. 

It  is  only  after  the  completion  of  the  decrustation  that  one  can  deter- 
mine the  extent  of  permanent  injury  to  the  skin.  If  the  crusts  have 
been  softened  off  by  unguentous  substances  or  mechanically  removed, 
small,  irregular  depressions  filled  with  granulating  tissue  show  where 
the  integrity  of  the  papillary  layer  of  the  skin  has  been  affected.  On 
the  spontaneous  shedding  of  the  crusts  these  areas  will  be  seen  as 
reddish,  cicatrized  excavations.  The  extent  of  scarring  depends  entirely 
upon  the  depth  to  which  the  destructive  inflammation  has  extended. 
Pocks  which  remain  encapsuled  within  the  epidermis  will  leave  no 
permanent  evidence  of  their  presence.  They  will  be  followed  by  reddish 
stains,  the  result  of  a  passive  hyperaemia  of  the  papillary  bloodvessels. 
These  discolorations  are  quite  disfiguring  in  themselves,  but  disappear 
in  the  course  of  a  few  months.  On  exposure  to  cold  the  reddish  stains 
acquire  a  bluish  or  purplish  appearance.  As  time  goes  on  the  reddish 
color  becomes  darker  and  eventuates  in  a  brownish  pigmentation.  This 
pigmentation  is  fortunately  less  conspicuous  and  less  persistent  on  the 
face  than  on  the  covered  surfaces.  Even  after  several  months  the 
trunk  and  limbs  frequently  exhibit  stains  of  a  cafe-au-lait  hue.  In 
persons  of  swarthy  complexion  and  in  negroes  the  pigmentation  is 
greater  than  in  fairer-skinned  individuals.  The  stains  in  the  African 
race  are  often  quite  black  and  appear  to  persist  longer  on  the  face  than 
in  Caucasians.  Where  the  true  skin  has  been  destroyed  in  negroes, 
the  normal  pigment  of  the  skin  is  frequently  lost.  In  such  cases  a 
whitish  or  pinkish  discoloration  is  seen  in  the  centre  of  the  scar,  with 
a  hyperpigmented  zone  surrounding  it. 

After  the  lapse  of  three  or  four  months  the  scars  of  smallpox  assume 
a  whitish  color,  paler,  indeed,  than  the  surrounding  integument.  They 
may  be  round,  oval,  linear,  stellate,  radiate  or  irregular,  according  to 
the  configuration  or  grouping  of  the  lesions  which  caused  them.  They 
may  be  large  or  small,  deep  or  shallow;  not  infrequently  they  present 
sharp,  overhanging  edges.  Indeed,  there  is  nothing  specially  char- 
acteristic about  the  pits  left  after  variola,  save  their  extent  and  distri- 
bution. Affecting  most  profusely  and  conspicuously  the  face,  they  give 
rise  to  the  well-known  "pock-marked"  countenance.  It  is  well  to 
remember,  however,  that  similar  pits  sometimes  follow  a  severe  acne, 
particularly  of  the  necrotic  type.  The  writers  have  seen  scarred  acne 
patients  who  might  have  passed  for  variola  subjects.  The  older  writers 
gave  to  acne  the  significant  title  of  "  stone  pock." 

By  a  curious  irony  of  fate,  nature  obHterates  the  remains  of  the  vast 


PLATE  XXI. 


Severe  Attack  of  Smallpox  in  an  Un vaccinated  W^onian.     Tenth 
day  of  Eruption.     Face  painted  with  tincture  of  iodine. 


77//';  SYMrT()MAT()IJ)(,'  Y  OF  ^'^fA  LLI'OX 


191 


majority  of  variolous  lesions  upon  the  covered  surfaces  of  the  body, 
whereas  indelible  evidence  is  left  upon  the  face  and  frequently  the 
hands  to  hear  witness  to  the  cruel  disease  through  which  the  patient 
has  passed.  Time,  however,  accomplishes  ninch  towarrl  the  (^ffacernent 
of  the  moi'c  superficial  scars  and  the  mitigation  of  tin;  disfigurement 
produced  by  the  deeper  cicatrices. 

The  hair  of  tlie  head,  beard,  eye})rows,  etc.,  may  be  lost  after  the 
termination  of  a  severe  smallpox,  especially  in  cases  in  which  the  erup- 
tion has  been  profuse  in  these  areas.  This  alopecia  is  probably  in  part 
of  febrile  origin  and  partly  the  result  of  the  local  iiifhiciice  of  the 
exanthem.     Restoration  of  the  hair  usually  occurs,  and  this  is  eomplete 


Fio.  33 


Deep  scarriug  aud  temporary  loss  of  hair  after  recovery  from  confluent  smallpox. 

except  in  areas  in  which  the  hair  papillae  have  been  destroyed  bv  the 
variolous  lesions. 

The  nails  of  the  fingers  and  the  toes  may  be  shed  in  severe  cases. 
This  is  usually  accomplished  slowly  through  the  pushing  off  of  the 
old  nail  by  the  new  one  growing  from  behind.  After  six  or  eioht  weeks 
a  sharp,  elevated  ridge  is  seen  near  the  nail  fold;  this  represents  the  free 
border  of  the  new  nail,  which  in  the  course  of  time  extends  forward. 
Not  infrequently  variolous  lesions  are  located  beneath  the  nail.  These 
subungual  pocks  are  of  a  purplish  or  reddish-brown  color,  looking  not 
unlike  traumatic  ecchymoses. 

When  convalescence  sets  in  in  uncomplicated  cases,  improvement  in 


192  SMALLPOX 

the  general  condition  of  the  patient  is  rapid.  The  appetite  returns  and 
is  apt  to  become  keen,  sometimes  even  voracious.  The  digestive  func- 
tions are  active  and  the  patient  rapidly  regains  strength  and  weight. 

Impetigo  Variolosa. — During  the  period  of  desiccation  and  incrusta- 
tion in  smallpox  certain  secondary  changes  commonly  occur  upon  the 
skin.  One  of  these  is  the  development  of  sparsely  distributed  blebs 
containing  a  thin,  dirty-yellow  fluid.  These  may  originate  in  several 
distinct  ways.  They  may  spring  up  upon  previously  healthy  inter- 
pustular  areas  of  skin,  or  they  may  result  from  a  direct  conversion  of 
the  pustules  into  blebs.  At  times  a  pustule  is  seen  one-half  of  which  is 
still  yellowish,  while  the  other  half  is  spreading  out  into  a  muddy-colored 
bleb.  The  blebs  are  commonly  flat,  although  at  times  they  rise  prom- 
inently from  the  surface;  they  vary  in  size  from  a  bean  to  a  walnut. 
The  epidermal  roof  is  flaccid,  wrinkled,  and  thin,  and  easily  disposed 
to  rupture,  when  a  thin,  yellowish  fluid  exudes,  which  dries  in  the  form 
of  irregular  crusts.  This  form  of  bleb  formation  is  most  frequently 
seen  on  the  hands  and  feet,  where  they  may  reach  a  diameter  of  an  inch 
or  more. 

Fig.  34 


^■<.,_ 

— -M!»i 

,,-«*«. 

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m 

m 

,: 

^"^ 

Bmi^ 

^ 

Variolous  impetigo,  showing  undermining  of  the  epidermis  around  the  dried  pocks  ;  appearing 
during  the  decline  of  the  eruption. 

A  more  common  change  in  the  pustules,  however,  is  the  development 
around  the  partially  desiccated  crust  of  a  reddish,  vesicular  ring,  con- 
taining a  turbid,  puriform  secretion;  just  beyond  the  border  of  the 
raised-up  epidermis  is  a  narrow,  pinkish  band,  which  indicates  the 
spreading  edge.  These  flat,  bullous  patches  spread  peripherally,  lifting 
up  the  epidermis  as  extension  takes  place,  until  perhaps  an  area  the 
size  of  a  silver  half-dollar  is  reached.  Central  crusting  proceeds  con- 
currently with  centrifugal  extension.  In  this  manner  large,  dirty-yellow, 
irregular,  friable  crusts  are  formed.  It  is  not  uncommon  for  most  of 
the  pustules  on  the  trunk  and  extremities  to  become  surrounded  by  a 
spreading,  vesicopustular  ring,  producing  an  extensive  secondary  erup- 
tion. Nearly  all  patients  with  unmodified  smallpox  present  these 
"sores"  upon  the  skin.  Where  the  eruption  is  profuse  there  may  be 
considerable  elevation  of  temperature  and  other  evidences  of  septi- 
caemia. Indeed,  this  extensive  secondary  skin  involvement  may  even 
cause  death. 

One  of  the  patients  at  the  Municipal  Hospital,  a  woman  aged  sixty 


THE  SYMPTOMA  TOLOfJ  V  OF  SMy\  LLI'OX 


103 


yeiirs,  wiis  jippiircnily  recovcM'iiifi;  Froiii  siriMllpox  wlicii  an  (.'Xtcnsive 
outbreak  of  tlic  clianu'tcr  (J('.sc;ril)(;(l  (J(;v('l()[)(;(l  mikI  led  to  a  fatal  t(-rrriina- 
tion.  The  crusts  in  this  case  were  numerous  iuid  vohiininoiis  an*!  left, 
after  removal  by  un^uentous  applications,  hu-^c  ;  in -as  of  (lcini<ic<l  skin. 
The  various  forms  of  j)ustul()-l)l('l)  foru)ati(ui  just  described  are  so 
common  in  sniidlpox  that  this  complicating;  condifif)!!  mi|j;ht  appro- 
priately be  dcsin;nated  iiiijxiifjo  variolosa.  Jndccd,  this  term  was 
employed  by  llebra'^  for  one  of  the  forms  of  bleb  formation  above 
referred  to.  In  1807  he  wrote:  "  In  other  instances  a  consecutive 
suppuration  a|)j)ears,  not  roimd  crusts  formed  from  variolous  pustules, 
but  in  tlu^  interveniufi^  s])aces  which  were  frc(;  from  the  cfHorcscence. 
Thus,  there  aj)pears  a  second  pustular  eruption,  which  might  almost 
be  regarded  as  a  second  smallpox  eruption,  were  it  not  that  the  pustules 
have  a  different  form,  and  take  a  different  course.    In  fact,  they  resemble 


Impetigo  variolosa  complicating  a  severe  attack  of  smallpox. 

rather  those  of  the  common  pustular  affections,  and  therefore  this 
affection  may  be  called  impetigo  variolosa."  Hebra  preceded  this 
description  by  a  reference  to  "central  crusts  with  small  vesicular  rings, 
containing  a  puriform  fluid,"  to  which  he  applied  the  name  rupia 
variolosa. 

Microscopic  and  cultural  examination  of  the  contents  of  variolous 
vesicles  and  pustules  demonstrates  that  the  ordinary  pyogenic  organisms 
are  absent  in  the  early  stages  of  the  lesions,  but  commonly  appear  during 
the  late  pustular  period. 

In  a  bacteriological  study  of  the  vesicles  and  pustules  of  smallpox" 
we  found  the  lesions  to  be  sterile  until  a  late  stage  of  the  eruption. 


1  Diseases  of  the  Skiu,  Translation  of  the  New  Sydenham  Society,  p.  251. 

-'  Schamberg.    Preliminary  Report  of  a  Study  of  the  Contents  of  the  Vesicles  and  Pustules  of 
Smallpox,  Journal  of  the  American  Medical  Association.  February  14,  1903. 

13 


194  SMALLPOX 

Of   34   cultures   of   fluid  from   variolous   lesions   before   the  seventb- 
■^^  day  of  the  eruption,  33  remained  sterile.     And  even  on  the    eighth, 
*"■   ninth,    and    tenth    days    bacteria    cultivable    on    ordinary  media    are 
not    infrequently    absent.      Of    a    total    of    82    cultures    made,    64, 
or  77  per  cent.,  failed  to  show  any  growth  whatsoever.     Frequently, 
thick,  creamy  pus  was  deposited  upon  nutrient  media  without  giving 
rise  to  any  colonies  whatsoever.     These  results,  which  are  in  accord 
with  most  similar  investigations,   suggest  that  the  _caw5a__cat*5^£_of^ 
smallpox,  which  is,  of  course,  resident  in  thelesioiis^is-itsdli^^pyogenic^ 
and  that  it  is  responsible  for  the  suppuration  of  the  variolous  pock. 
Suppuration  is,  therefore,  to  be  regarded  as  a  part  of  the  normal  evolu- 
tion of  the  eruption  of  smallpox.    After  the  eighth  or.iiiiith_-day.jof  the^ 
eruption,  however,  it  would  appear  that  a  secondary  Jnfedion^Hith,. 
germs  conimonly  present  on  the  skin,  takes  place.    At  this  ti«3-ea?:arioJi.ous 
impetigo  develops.    The  thin,  seropurulent  fluid  in  the  impetigo  blebs, 
when  examined  in  smear,  is  seen  to  contain  myriads  of  micro-organisms, 
-abiefly- .streptococci,  although    staphylococci    and  a  pseudodiphtheria 
bacillus  are  also  found.     Cultures  of  this  fluid  or  of  the  material  from 
the  flat  impetigo  lesion  around  the  variolous  crusts,  invariably  give  rise 
to  growths  of  these  several  organisms  alone  or  combined.    Fluid  from 
a  large  bleb  was  injected  beneath  the  skin  of  a  dog;  in  a  few  days  a 
local  tumefaction  the  size  of  a  walnut  developed,  which  became  sur- 
mounted by  a  dime-sized  bleb.     This  ruptured  and  left  a  superficial 
ulceration.     The  swelling  disappeared  and  recovery  occurred  without 
any  further  local  or  general  symptoms.  ^  When  deatl]__occurs^iji_jmall-  ^ 
j)OX;_ streptococci  may^injthe  vast  majority l)f"mstances,  be  recovered^ 
'^,fpem-ihe-^elH~i£53r.ather  intjernaT  organisms.     Most  of  the  deaths  in 

sma-llpox-oecur. Jbcom  septicaemia  from  the  ninth  to  the  eleventh  day 

of  the  eruption.  ~"    -—-"-'—«„.. 

As  is  well  known,  the  commonest  complications  of  smallpox  are 
boils  and  subcutaneous  abscesses.  Seldom  does  a  well-marked  case 
of  variola  vera  finish  its  course  without  being  accompanied  by  furuncles 
and  phlegmonous  infiltrations.  We  have  been  impressed  with  the  fact 
that  the  tendency  to  these  complications  is  increased  by  a  pre-existent 
severe  variolous  impetigo. 

Cutaneous  gangrene  occasionally  occurs  during  the  course  of  small- 
pox; we  observed  this  complication  about  a  half-dozen  times  in  the 
Municipal  Hospital  during  the  recent  epidemic  of  1901 -'04.  These 
cases  are  commonly  preceded  by  an  extensive  impetigo  variolosa. 
Fig.  36  shows  a  patch  of  gangrene  on  the  inside  of  the  thigh  in  a 
patient  who  had  a  severe  impetigo.  This  patient  was  desperately  ill 
with  septicsemic  symptoms,  but  ultimately  recovered. 

The  statement  appears  to  be  justified  that  impetigo  variolosa  increases 
the  liability  to  the  deeper  pyogenic  infections,  such  as  boils,  abscesses, 
erysipelas,  and  cutaneous  gangrene.  It,  moreover,  appears  to  bear  a 
relationship  in  many  cases  to  the  development  of  certain  postvariolous 
rashes  presently  to  be  described. 

It  has  been  our  practice  at  the  Municipal  Hospital  to  give  antiseptic 


77/ a;  symptom  a  TOLOd  Y  OF  SMA  fJJ'OX 


195 


baths  to  smallpox  patients  fluring  the  late  sn[>pijrative  sta^e  of  the 
disease.  The  patient  is  irninc^rsed  for  fifteen  or  twenty  rninut(!S  in  a 
bath  eonsisting  of  a  1  :  I (),()()()  to  1  :  20,000  sohition  of  corrosive  sub- 


Gangrene  of  the  skin  complicaUng  severe  smallpox  ;  recovery. 
Fig.  .S7 


Uangiene  of  the  skin  accompanying  a  severe  smallpox  ;  ultimate  recovery. 


196  SMALLPOX 

limate.  In  other  cases  we  have  employed  a  1 :  500  solution  of  creolin. 
After  the  bath  the  patient  is  dusted  with  weak  antiseptic  powders.  This 
course  of  treatment  has  a  beneficial  influence  in  drying  up  the  impetigo 
sores  and  in  lessening  the  tendency  to  deeper  infection. 

Secondary  Toxic  or  Septic  Rashes. — Another  secondary  eruption  in 
smallpox,  to  which  but  little  reference  has  been  made  in  literature,  is  the 
toxic  or  septic  rash  which  appears  in  a  certain  percentage  of  cases  during 
the  stage  of  decrustation.  Between  the  eighth  and  eighteenth  days,  and 
most  commonly  on  the  thirteenth  or  fourteenth,  there  develops  upon 
the  trunk,  extremities,  and  at  times  the  face,  a  peculiar  erythematous 
efflorescence.  In  most  instances  the  rash  consists  of  a  diffuse,  dusky 
redness  bearing  a  strong  resemblance  to  the  exanthem  of  scarlet  fever 
{scarlatinijorm  erythema).  At  times  it  is  mottled  and  inclined  to  become 
somewhat  morbilliform  in  appearance.  The  scarlatiniform  eruption  is 
peculiar  in  that  the  skin  immediately  surrounding  the  drying  pocks  is 
often  exempted,  producing  a  sort  of  anaemic  halo.  The  rash  lasts  for 
two  or  three  days  and  then  fades  away.  If  the  erythema  has  been  well 
marked  it  is  prone  to  be  followed  by  desquamation,  which  may  be  most 
profuse  in  character.  The  exfoliation  of  the  epidermis  is  usually  rapid, 
and  may  be  out  of  proportion  to  the  intensity  of  the  rash.  Fig.  78  shows 
desquamation  of  the  cuticle  of  the  palms  in  large  masses  on  the  sixth 
day  of  the  rash.  In  this  patient  the  eruption  was  quite  indistinguishable 
from  that  of  scarlatina.  In  occasional  instances  a  most  inordinate  and 
persistent  desquamation  follows.  A  young  lad  developed  on  the  four- 
teenth day  of  the  smallpox  eruption  a  severe,  deep-red  erythema,  which 
was  followed  by  repeated  exfoliation  of  the  epidermis.  This  patient 
desquamated  four  or  five  distinct  times,  the  whole  process  extending 
over  a  period  of  six  or  eight  weeks.  Handfuls  of  scales  could  be  daily 
gathered  from  his  bed.  The  hair  of  the  scalp  and  eyebrows,  and  the 
finger-nails  were  subsequently  lost.  A  patient  recently  in  the  hospital 
passed  through  an  almost  identical  attack.  Such  cases  merit  the  desig- 
nation of  dermatitis  exfoliativa  variolosa. 

In  rare  instances  these  secondary  rashes  may  become  hemorrhagic. 
Hgemic  extravasation  into  the  skin  is  most  apt  to  occur  upon  the  lower 
extremities,  where  the  stasis  in  the  vessels  is  greater  owing  to  gravity. 

We  have  seen  a  severe  secondary  purpuric  rash,  the  history  of  which 
is  of  sufficient  importance  to  warrant  its  presentation : 

H.  W.,  an  unvaccinated  boy,  aged  seven  and  a  half  years,  was  admitted 
to  the  hospital  on  September  28,  1901,  on  the  fourth  day  of  the  smallpox 
eruption.  The  attack  was  severe,  the  eruption  being  semiconfluent. 
The  patient  did  well  for  seven  or  eight  days.  On  the  thirteenth  day 
of  the  eruption,  the  face,  on  which  the  swelling  had  largely  subsided, 
again  became  tumefied,  the  temperature  rose,  and  a  profuse  macular 
eruption,  rapidly  becoming  purpuric,  and  consisting  of  bluish-red  pin- 
head  to  finger-nail-sized  ecchymoses,  developed  over  the  trunk  and 
extremities.    The  patient  sank  rapidly  and  died  in  two  days. 

The  secondary  rashes  are  not  infrequently  accompanied  by  rise  of 
temperature.     The  temperature  may  suddenly  mount  to  104°,  decline 


PLATE    XXIV. 


Exfoliative  Dermatitis  Occurring  during  tlie  Course 
of  a  Severe  Smallpox. 


THE  S  VMI'TOMA  TOIJX;  V  OF  SMA  LIJ'OX  ]  U7 

rapidly,  and  tlien  remain  for  some  days  in  (lie  nei|^lil)0)'liof»d  of  lOT'  oj- 
102°  F.  Jii  some  palienls,  witli  rnslx'S  of  nioder;i(e  sev(;ri(y,  no  [jyrexial 
elevation  oeeiirs.  WliiK;  tlie  eruption  lasts  tli(^  |);i(ients  are,  as  a  rule, 
sonniolent,  extremely  irritable,  and  eonsiflerahly  prostrated.  The 
rashes  are  more  eoinmonly  ol^served  in  patients  who  have  had  severe 
smallpox  eruptions. 

Durinf)^  the  epidemie  of  1901-03,  we  observed  these  eruptions  in 
perhaps  5  per  eent.  to  8  per  eent.  of  all  patients  admitted.  'J'he 
incidence  among  children  seemed  to  be  greater  than  among  adults. 
In  the  severe  epidemic  of  smallpox  in  1871-72,  such  rashes  were 
much  less  fre(|uently  observed,  and  in  the  year  1904  they  were  distinctly 
less  frequent  than  in  the  two  preceding  years. 


J^e  scarlatiniform  eruption  is  the  type  b^^^r  most  commonly  seen. 
The  resem blance  to  IKe^rasn  oi  'scarlerlever  is  so  strong  that  in  the 
beginning  the  existence  of  the  latter  disease  was  suspected.  In  a  small- 
pox hospital  in  a  neighboring  town,  several  patients  with  scarlatincjid 
rashes  of  the  character  referred  to  were  believed  to  be  suffering  fi'om 
scarlet  fever  and  were  promptly  isolated.  The  physician,  during  a 
visit  to  our  wards,  identified  the  toxic  rashes  with  the  eruption  he  had 
observed. 

Perhaps  some  of  the  cases  of  scarlet  fever  associated  with  smallpox 
reported  by  the  older  writers  were  in  reality  instances  of  scarlatiniform 
erythema. 

In  a  boy  recently  treated  in  the  hospital,  a  severe  variolous  impetigo 
developed,  and  this  was  followed  on  the  fourteenth  day  of  the  smallpox 
eruption  by  an  intense  macnlopapular  rash,,  which  was  on  the  trunk 
quitejiidisthiguishable  from  measles;  on  the  face,  however,  there  was 
relatively  little  eruption.  The  duration  of  the  eruption  was  brief,  and 
catarrhal  symptoms  were  absent. 

_  The  postvariolous   rashes.,  are  in  all    probability  septic  or  toxic  in 
character,   due  doubtless  to  the  absorption  of  some   j^oisoii  into  the' 
blood.     Our  experience  in  the  Municipal  Hospital  would  indicate  that 
these  are  more  common  in  patients  who  have  been  the  subjects  of  an 
abundant  impetigo. 

As  far  as  we  have  been  able  to  ascertain,  none  of  the  modern  text- 
books or  monographs  on  smallpox,  save  the  article  by  Moore,  make 
mention  of  these  rashes.  The  earlier  writers  doubtless  regarded  the 
development  of  the  erythema  as  evidence  of  an  intercurrent  scarlet 
fever,  and  the  numerous  instances  of  the  coincidence  of  these  two 
diseases  may  thus  be  accounted  for. 

Simon,^  in  an  article  on  scarlatina  and  scarlatiniform  eruptions  in  the 
course  of  smallpox,  written  in  1873,  carefully  distinguished  these  two 
conditions  and  reported  cases  representing  both  true  scarlet  fever  and 
the  secondary  erythema  which  resembles  it.  In  the  latter  cases  he 
considers  the  diagnosis  of  scarlet  fever  excluded  by  the  date  of  onset  of 

1  Ueber  Scharlach  und  Scharlach-aebnliche-ausschlage  im  Verlauf  der  Variola,  Archiv  f.  Der- 
matologie  u.  Syphilis,  1873,  p.  115. 


198  SMALLPOX 

the  complication,  the  absence  of  adequate  invasive  symptoms,  the  mild 
character  of  the  angina,  the  absence  of  or  slight  character  of  the  des- 
quamation, and  the  non-contagiousness  of  the  condition. 

Of  thirteen  cases  of  secondary  rash,  Simon  observed  nine  develop 
after  the  tenth  day  of  the  variolous  eruption.  A  few  were  seen  as  early 
as  the  sixth  day  and  as  late  as  the  eighteenth  or  twentieth  day.  Simon 
does  not  seem  to  have  encountered  the  profuse  desquamation  which 
has  occurred  in  some  of  our  cases.  No  mention  is  made  by  him  of 
morbilliform  rashes. 

According  to  Simon,  Fleischmann  also  saw  some  of  these  cases,  as 
did  likewise  Bernouilli,  who  states  that  in  1865  he  saw  a  case  of  secondary 
erythema  in  variola  which  he  erroneously  regarded  as  an  intercurrent 
attack  of  scarlet  fever. 

The  only  other  reference  to  these  rashes  that  we  have  been  able  to 
find  is  by  Meredith  Richards,^  Medical  Officer  of  Health  of  Chesterfield, 
England.  This  writer  refers  also  to  the  bullous  and  pustular  eruptions 
occurring  late  in  the  course  of  variola.    He  says: 

"  Less  known,  and  from  a  practical  point  of  view  less  important,  are 
certain  posteruptive  rashes,  which  include  (1)  a  scarlatiniform  erythema, 
general  in  distribution,  and  not  differing  from  that  common  in  various 
septic  states;  (2)  a  development  of  the  smallpox  pustules  which  appears 
to  correspond  to  what  Dr.  Crocker  has  recently  described  as  "impetigo 
contagiosa  gyrata."  The  smallpox .  pustules,  instead  of  drying  up  and 
scabbing  on  the  eleventh  day,  show  signs  of  spreading  peripherally,  so 
that  in  a  day  or  two  many  of  the  lesions  consist  of  three  well-defined 
parts,  viz.,  a  central  scab,  a  surrounding  vesicular  ring  which  rapidly 
becomes  pustular,  and  a  red  areola  surrounding  the  pustular  ring. 
Unless  treated,  the  areola  and  pustular  ring  continue  to  spread  centrif- 
ugally  until  the  whole  lesion  may  measure  an  inch  or  more  in  diameter. 
When  abundant,  this  rash  gives  rise  to  a  very  remarkable  appearance, 
and  is  clinically  important  because  it  is  often  attended  by  high  temper- 
ature and  other  signs  of  septicaemia.  There  is  no  doubt  that  this  is  due 
to  a  mixed  infection,  as  it  has  a  tendency  to  occur  in  particular  wards 
and  may  be  accidentally  acquired  by  attendants.  It  also  merits  notice 
in  passing,  as,  I  believe,  this  variety  of  secondary  infection  has  not  been 
fully  described.  (3)  Accompanying  the  previous  rash  or  occurring  in 
other  cases  exhibiting  signs  of  septicaemia,  it  is  not  infrequent  to  observe 
cases  in  which  the  healthy  interpustular  epidermis  is  raised  into  flaccid 
bullae,  containing  a  few  drops  of  foul,  mucopurulent  fluid.  These 
bullae  are  soon  followed  by  profuse  desquamation,  which  may  lead  to 
the  shedding  of  the  nails,  and  are  accompanied  by  severe  constitutional 
symptoms  of  a  septicaemic  character.  Many  of  them  are  fatal,  though 
a  good  proportion  appear  to  owe  their  lives  to  boracic  baths  combined 
with  good  nursing  and  general  tonic  treatment." 

1  Accidental  Rashes  Occurring  in  the  Course  of  the  Exanthemata,  Quarterly  Medical  Journal, 
1896,  p.  31. 


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77//';  vmuI':tii<:s  01'  sMALLi'ox  199 


THE  VARIETIES  OF  SMALLPOX. 


The  course  jnst  described  relates  more  particularly  to  that  form  of 
the  disease  iu  which  the  eruption  is  either  discre/e  or  jiiuuMM44rflifYmf:'-  In 
our  ex[)erieuce  the  yast  iuajority  of  cases  met  with  Ijelon^  to  the  last- 
najned  v.-iriety  that  is  to  say,  the  eruption  is  usually  cither  partially 
or  wholly  condiiciil  on  llic  face,  the.dorsal  surfaces  of  the  hauds,  and 
the  lower  portions  of  the  f(jrearms,  while  on  the  trunk  and  extremities 
"^jt  is'HiscrHe,  save  a  few  lesions,  j)erha{)s,  which  may  coalesce.  Varia- 
tions'^" the  extent  of  the  eruption  may  reach  extreme  limits,  from  a 
few  small  pustules,  scarcely  characteristic  enough  to  enable  one  to  defi- 
nitely proclaim  the  variolous  nature  of  the  disease,  to  the  most  extensive 
eruption  covering  the  entire  cutaneous  surface.  Between  these  two 
extremes  there  may  occur  numerous  grades  of  intermediate  severity. 

Confluent  Smallpox  (Variola  Confluens).— It  can  hardly  be  said  that 
there  is  any  symptom  during  the  initial  stage  of  smallpox  peculiar  to 
the  confluent  form  of  the  disease.  Inasmuch,  however,  as  the  symptoms 
preceding  this  type  of  variola  are,  with  great  uniformity,  of  a  severe 
character,  this_g£ave.  jo rm  may  be  excluded  in  tlie  presence  of  mild., 
initial  manifestations.  Most  prominent  among  the  early  symptoms 
-"aTe'severe  headache,  persistent  retching  and  vomiting,  delirium,  or,  in 
children,  stupor,  violent  pain  in  the  back,  and  high  fever.  The  tem- 
perature always  rises  rapidly,  and  attains  frequently  an  extraordinary 
height.  It  is  not  at  all  uncommon  for  the  fever  to  reach  105°  or  106°, 
F.  and  cases  have  been  recorded  in  which  a  temperature  of  110°  F.  w^as 
registered.  .  Qn.the  third,  fourth,  or  fifth  day  of  the  eruption  the  tempera- 
ture declines,  but  this  remission  is  never  as  complete  as  in  milder  cases, 
'nor  does  it  continue  as  long.  Xl\inng  the  remission  the  temperature  is 
"^iibt  far  from  101°  or  102°  F. ,  at  which  point  it  is  apt  to  remain  for  a  period 
"ortwo  or.  three,  days,  when  the  secondary  rise  commences.,.  The  fever, 
^iiring.  the  stage  of  suppuration,  is  not  usually  as  intense  as  in  the  initial 
stage,  yet  it  may  at  times  rise  considerably  higher.  The  chart  shown 
upon  page  1S4  illustrates  the  temperature  curve  of  a  severe  case  of  con- 
fluent smallpox,  and  may  be  taken  as  a  fair  type  of  the  cases  of  this 
class.  It  may  be  well  to  add  that  the  temperature  in  the  suppurative 
stage  was  somewhat  influenced  by  the  use  of  antipyretics. 

It  is  sometimes  stated  that  the  eruption  of  confluent  smallpox  develops 

early,  often  on  the  second  day  of  the  initial  fever.    Our  experience  leads 

us  to  believe  that  this  variety  develops  less  rapidly  than  in  modified  , 

"^Torms  of  the  disease,  but  there  is  a  shorter  interval  between  the  time^ 

"of  its  appearance  on  the  face  and  on  other  portions  of  the  body.     So 

quickly  is  the  eruption  diffused  over  the  whole  body  that  it  has  been 

mistaken  in  the  papular  stage  for  measles.    -Indeed,  it  is  the  confluent 

form  of  variola  which  is  particularly  apt  to  be  confounded  with  mor- 

^  billi.    Ordinarily  in  forty-eight  hours  the  efflorescence  has  covered  the 

entire  body  surface.     Owing  to  the  extensive  involvement  of  the  skin, 

redness  and  swelling  begin  early.     The  face  is  intensely  h}^ersemic 

and  the  seat  of  distressing  burning  and  itching.    The  marked  suffusion 


200  SMALLPOX 

of  the  countenance  frequently  enables  one  to  prophesy  that  the  disease 
will  take  the  confluent  form.  As  the '  eruption  progresses  it  passes 
through  the  usual  stages,  though  somewhat  more  slowly  than  in  the 
milder  cases.  The  papules  are  thickly  set,  and  even  at  this  stage  a 
coalescence  of  lesions  may  be  noted.  The  skin  is  thickened  and  indu- 
rated, and  feels  like  embossed  leather.  Soon  the  grayish  outlines  of 
the  vesicles  make  their  appearance  and  the  confluent  aspect  of  the 
exanthem  becomes  accentuated.  With  the  conversion  of  the  vesicular 
contents  into  pus,  great  swelling  and  oedema  develop,  particularly  about 
the  face  and  scalp.  The  eyelids  are  enormously  puffed,  and  the  margin 
of  the  upper  lid  so  greatly  thickened  that  it  completely  overlaps  the 
lower.  The  nose,  lips,  and  ears  are  swollen  and  distorted,  imparting 
to  the  countenance  a  most  hideous  expression.  The  transformation 
of  the  features  is  so  rapid  and  complete  that  nurses  and  physicians  who 
are  off  duty  for  a  day  or  two  are  frequently  unable  to  identify  such 
patients  on  their  return  to  the  wards.    The  hands  and  feet  are  swollen 

Fig.  38 


Profuse  eruption  upon  hands. 

to  double  their  natural  size,  and  are  most  exquisitely  tender  and  painful. 
When  full  pustulation  is  established  the  neighboring  lesions  coalesce 
and  form  large,  flat  blebs.  In  severe  cases  the  walls  of  the  pustules  are 
completely  swept  away,  producing  flat,  purulent,  pasty-looking  infiltra- 
tions of  enormous  proportions.  W^hen  the  pus  exudes  upon  the  sur- 
face and  dries,  a  most  disgusting  stench  arises  from  the  body. 

In  favorable  cases,  with  the  beginning  of  desiccation,  a  subsidence 
in  the  oedema  takes  place,  and  the  crusts  are  cast  off  from  the  skin.  The 
decrustation  is,  however,  slower  than  in  the  discrete  and  semicon- 
fluent  forms  of  the  disease.  TJie  suppurative  proces§uis*de^,grand 
iiKJjQe  pergigjtsnt,  and  may  lead  to  the  consecutive  production  inme 
same  areas  of  large  crusts  which  are  successively  thrown  off  as  they 
form.  Owing  to  the  greater  depth  of  the  purulent  inflammation  in  the 
integument,  more  extensive  destruction  of  the  true  skin  occurs  and 
consequently  the  scarring  is  deeper  and  more  conspicuous.  Instead 
of  discrete  pits  the  face  may  be  seamed  with  scars  in  a  most  frightful 
manner. 


77/  a;  va  luicri  i':s  o  !<•  sMy\  l  li-ox  201 

In  severe  cases  which  are  going  to  (cnniiijii*;  i;i(;illy  tin-  ccjursc  pm- 
.snTuT  isTaTIi('rT!ino'rv"i"iit  froin  llial,  above;  (lc.scrilM'<l.  TIk;  cvolulioii  ol'  the 
erunlioii  is  excessively  slow,i  Uic  lesions  appearing  lo  he  siij>pie.s.sed  and 

•^ccomp;iiii<'il  I))  l)nt  little  swelling.  'J'he  face  has  a  peculiar  hinrrerl 
appeaniiiee.  Tlie  older  writers  regarded  the  swelling  of  the  face  as  a 
favoral)l(!  sign,  inasmneh  as  it  indicated  a  certain  vigor  of  the  consti- 
tution. Physicians  who  have  had  cx[)erience  with  smallpox  will  rcco'^- 
nize  the  correctness  of  this  observation.  ^wplUng  of  the  features  is  to 
be  weJcom,ed.-aa., a, favorable  indication,  and  the  absence  of . jpedema,  iii 
confluent    eruptions    must,  be  regarded   with    grave    foreboding.     An 

'*ft1ffimo'us  sign  in  these  cases  is  the  early  development  of  flat,  brownish, 
depressed  scabs  on  a  few  of  the  vesicles  on  the  forehead  and  cheeks. 
In  these  suppressed  eruptions  the  vesicles  are  only  partially  filled  with 
fluid,  and  the  features  are  only  slightly  swollen;  the  skin  is  roughened 
and  presents  a  somewhat  parchmenty  appearance.  There  is  most 
profound  prostration,  and  death  results  in  almost  every  case. 

Fig.  39 


Swelling  of  the  face  on  the  seventh  day  in  a  fatal  case  of  smallpox. 

In  confluent  smallpox:  the  mucous  membrane  of  the  mouth,  throaty 
and_  nose  H  always  severely  involved.  The  epithehum  of  these  parts 
Ti^equently  becomes  so  completely  disorganized  by  the  eruptive  process 
that  it  presents  the  appearance  of  diphtheritic  membrane.  Swelhng 
of  the  tonsils  and  soft  palate  is  often  so  great  as  to  cause  the  greatest 
difficulty  in  swallowing.  It  is  in  the  intensely  confluent  cases  that 
glossitis  variolosa  is  apt  to  occur.  The  parotid  gland  sometimes  becomes 
acutely  inflamed,  perhaps  by  extension  along  the  ducts  of  Steno.  Pro- 
fuse expectoration  of  saliva  is  not  infrequently  noted.  The  pharvnx 
and  larynx  are  almost  always  the  seat  of  an  extensive  eruption,  giA'ing 
rise  to  dysphagia,  hoarseness,  and  aphonia.  Acute  oedema  of  the  glottis 
is  one  of  the  most  serious  accidents  to  which  this  form  of  the  disease  is 
liable;  when  it  develops  the  patient's  life  is  placed  in  imminent  danger. 
At  a  somewhat  later  period  serious  submucous  infiltrations  of  pus  may 
develop,  producing  tonsillar  or  postpharyngeal  abscesses  or  perichondritis 
of  the  larynx. 


202 


SMALLPOX 


The  constitutional  symptoms  during  the  suppurative  stage  of  con- 
fluent variola  are  most  pronounced.  There  is  marked  pyrexia  (104°  to 
105°  F.),  rapid  pulse,  frequent  cough  and  expectoration,  great  restless- 
ness, inabihty  to  sleep,  and  profound  prostration.  Dehrium  is  very 
common,  but  the  patient  does  not  become  maniacal  as  he  often  does 
earlier  in  the  disease.  At  this  stage,  also,  complications  are  liable  to 
occur,  such  as  corneal  ulcer,  keratitis,  pleurisy,  empyema,  suppuration 
of  the  joints,  celluhtis,  phlegmonous  inflammations,  and  gangrene  of 
the  skin.  Vomiting  and  diarrhoea  may  supervene,  and  still  further 
exhaust  the  patient's  ebbing  vitality.  In  fatal  cases  the  patient  sinks 
into  a  comatose  condition,  the  pulse  becomes  excessively  rapid,  and 
the  temperature  not  infrequently  rises  to  105°,  106°,  or  107°  F.  Thus 
closes  the  final  chapter  in  one  of  the  most  distressing,  cruel,  and  frightful 
diseases  "to  which  human  flesh  is  heir." 


Fig.  40 


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W.  F.,  aged  thirty-seven  years.  Case  of  smallpox  ia  an  un vaccinated  man,  showing  the  rise  of 
temperature  in  the  initial  stage ;  the  secondary  or  suppurative  fever,  and  a  later  irregular  fever  due 
to  ai  scesses  and  cellulitis  ;  recovery. 


\ 


The  mortality  rate  in  confluent  smallpox  varies  in  different  epidemics, 
but  it  is  always  extremely  high.  In  general  terms  it  may  be  stated  that 
_^.le,ast  one-half  of  such  cases  perish.  When  this  form  of  the  disease 
terminates  in  recovery  it  is' tmlyafter^  long  and  tedious  convalescence, 
interrupted  by  the  development  of  boils,  abscesses,  and  other  compli- 
cations. 

Hemorrhagic  Smallpox. — Of  all  the  forms  of  variola  the  hemorrhagic 
is  the  most  formidable  and  mahgnant.  .-For.  those  w-ho  contract  a-.-Wjellr. 
,j3aarked  attack  ot  this  type  of  the  disease  there  is  absolutely  no  hope. 

According  as  the  hemorrhage  precedes  or  follows  the  appearance  of 
the  variolous  lesions,  two  varieties  are  distinguished:  (1)  the  so-called 
\^urpura  variolosa,  in  which  the-hemorrbage  js  the  primary  exanthem; 
(2)  variola 'pustulos a  hemorrhagica,  in  which  it  comes  on  secondarily. 

In  certain  epidemics  a  petechial  eruption  is  frequently  seen  at  the 
close  of  the  initial  stage  of  the  disease,  at  or  about  the  time  when  the 
eruption  should  appear.     This  symptom  often  precedes  the  purpuric 


77//';  vAniH'i'iKs  ()!<•  sMMj.rox  20;i 

or  hemorrhagic;  lonii  of  the  disease,  and  is  IIk  rcl'orc,  as  a  rule,  an  early 
sign  of  inaligiiiiMcy.  At  other  tiiDcs  pclcchiic  and  cfc-hymoscs  af>)jear 
between  tlie  j)a|)iiles  or  vesicles,  or  (h-vclo])  actually  in  the,  bases  of 
these  lesions.  The  vesicles  and  [)ustules  may  contain  })nrulent  material 
or  m;i,y  fill  up  witli  sanguinopurulent  fluid.  Consiclerahle  diversity 
of  ;i[)j)(!arance  is  sometimes  manifested  in  the  eruption  of  a  single  case. 
There  is  no  satisfactory  explanation  at  hand  io  elucidate  the  causation 
of  hemorrhagic  small{)OX.  It  wf)uld  aj)pear  that  the  determining  factor 
is  largely  resident  in  the  individual,  inasmuch  as  such  cases  may  be 
derived  from  ordinary  smallpox,  and,  on  the  other  hand,  may  give  rise 
to  the  usual  forms  in  other  people.  The  frequency  of  this  form  of  the 
disease  varies  in  different  epidemics,  being  commonest  when  a  more 
malignant  type  of  the  disease  prevails.  It  is  well  known,  for  example, 
that  hemorrhagic  variola  was  exceptionally  common  during  the  virulent 
pandemic  of  smallpox  in  1871-72. 

Variola  Purpurica. — Variola  purpurica,  or  purpura  variolosa,  is  the 
gravest  and  most  malignant  form  that  smallpox  can  assume.  Zuelzer 
has  called  attention  to  the  observation  that  4h€period,Qf  incubation  in 
hemorrhagic  smallpox  is  not  infrequently  abridged  to^six. or  eight  days. 
The  initial  stage  does  not  differ  essentially  from  that  of  ordinary  variola. 
The  patient  suffers  from  chill,  fever,  and  headache,  although  the  temper- 
ature is  not  as  likely  to  reach  so  extraordinary  a  height  as  in  confluent 
smallpox.  The  pain  in  the  back  is  usually  violent,  and  prostration 
excessive.      Furtheriu7)reV'°ihe':"p^^  siiffers   from    precordial 

"Histfess,  and  from  severe  retching  and  vomiting.  The  vomiting  in  this 
iorraj)|  the  disease  is  a  most  distressing  symptoni,  and  commonly  proves 

Miiore  persistent  than  in  ordinary  smallpox.  It  not  iiifi((|ueiirly  eon- 
yjmes^QI_seYeral  days  after  the  appearance  oi  the  exantliem.  Toward 
the  end  of  tlie  initial  stage  a  diffuse  efflorescence  appears  on  various 
parts  of  the  trunk  and  extremities,  while  the  face  remains  for  a  time 
exempt.  The  rash  is  at  first  scarlatinoid  in  appearance,  and  disappears 
partially  under  digital  pressure;  later  it  becomes  more  intense  and  of 
a  deeper  hue,  ancl  hemarrhagic., extravasation  into  the  skin  occurs. 
Petechia^  vibices",  and  ecchymoses  develop  upon  the  chest,  axilla^,  lower 
portion  of  the  abdomen,  the  groins  and  legs;  the  dark-red  or  purplish 
discoloration  now  present  no  longer  fades  away  under  pressure  of  the 
finger.  The  discoloration  rapidly  extends  to  the  face,  which  becomes 
dusky  red  or  livid  and  swollen.  .The  conjunctivae  are  injected,  the  eyes 
bloodshot,  and  the  lids  bluish,  owing  to  hemorrhage  into  the  cellular 

"tissue.  Frequently  the  extravasation  of  blood  under  the  conjunctiva 
covering  the  sclerotica  is  so  great  as  to  cause  this  membrane  to  project 
bgyonalhe  lids,  like  a  sac  hlled  with  blood.     Under  siich 'conditions 

"th-e-pfttreTTt^is  unable  to  completely  close  the  eyes.  The  cornea  retains 
its  normal  transparent  appearance, but, owing  to  the  elevated  conjimctiva 
about  its  periphery,  appears  to  be  sunken  deeply  into  the  eyeball. 
This  condition,  together  with  the  dark  discoloration  of  the  face  and  the 
tumefied  features,  gives  to  the  patient  a  peculiarly  unnatural  expression. 
A  close  scrutiny  of  the  skin  usually  reveals  the  presence  of  small  abortive 


204  SMALLPOX 

i^  vesicles,  which  may  be  almost  obscured  by  the  purplish  ecchymoses 
upon  which  they  may  be  situated.  These  are  most  apt  to  be  found  upon 
the  forehead,  axillae,  groins,  or  wrists.  The  vesicles,  which  are  of  a  plum- 
qolgred  or  -leaden-gray  tint,  never  develop  to  any  extent,  I mt,  remain 
perfectly  flat.  As  the  disease  progresses  the  discoloration  of  the  skin 
deepens  on  all  parts  of  the  body,  giving  to  the  integument  a  deep-indigo 
hue,  which  at  times  almost  approaches  black.  In  such  cases  it  is  difficult 
to  say,  judging  from  the  skin  alone,  that  the  patient  is  not  of  African 
origin.  Hence,  this  form  of  the  disease  has  been  known  as  black 
smallpox,  or  variola  nigra. 
,^The- eruptive  process  does  not  always  present  imequivocal  evidence^ 
of  smallpox,  for  there  may  be  complete  absence  of  true  va~riele«s-ksiQjiSu__ 
A  young  woman  was  admitted  to  the  Municipal  Hospital,  during  the 
spring  of  1902,  who  exhibited  upon  the  skin  nothing  save  a  universal 
scarlatinoid  eruption  of  dusky  hue.  No  vestige  of  papulation  or  vesicu- 
lation  was  present.  There  was  hemorrhagic  extravasation  beneath  the 
sclerotic  conjunctiva,  and  bleeding  from  the  mouth,  kidneys,  and  uterus. 
The  diagnosis  was  rendered  possible  in  this  patient  by  tlie  characfer 
of  the  initial  illness,  and  the  prevalence  at  the  time  of  an  epidemic  of 
smallpox.  In  another  case,  observed  in  a  young  man  some  years  ago, 
the  eruption  consisted  of  numerous  petechise  and  ecchymoses,  but  no 
lesions  distinctively  variolous  were  present.  Such  eruptions  might 
readily  be  confoupded  with  those  of  malignant  scarlatina  or  measles, 
or  purpura  hemorrhagica.  Patients  presenting  manifestations  of  this 
character  were  not  uncommonly  seen  during  the  very  malignant  epi- 
demic of  1871-72. 

In  this,  as  in  other  types  of  variola,  the  pharynx  and  upper  part  of 
the  respiratory  passages  participate  in  the  eruption.  There  is  apt  to 
be  more  or  less  cough,  with  bloody  expectoration.  The  tongue  is  large 
and  red  and  covered  with  blackish  blood  crusts,  which  may  also  be  seen 
on  the  lips.  A  fa; tor  peculiar  to  this  form  of  the  disease  is  exhaled;  it 
is  of  a  sickening  character,  and  suggests  stale  or  decomposing  blood. 
Purplish  spots  may  be  seen  upon  the  gums,  palate,  tongue,  and  buccal 
surfaces,  but  the  general  mucous  membrane  is  usually  pale.  Hemor- 
rhages are  quite  certain  to  occur  from  the  nose,  bronchial  mucous 
membrane,  kidneys,  rectum,  and  uterus.  Vomiting  of  blood  occurs  in 
quite  a  large  percentage  of  cases,  and  bloody  stools  are  by  no  means 
infrequent.  Indeed,  blood  may  issue  from  any  or  all  of  the  mucous 
surfaces  of  the  body;  we  have  even  seen  a  sanguinolent  fluid  ooze  from 
the  eyes.  Women  almost  always  suffer  from  severe  metrorrhagia,  and, 
if  pregnant,  commonly  abort.  The  temperature  is  seldom  high,  usually 
100°  F.  or  thereabouts;  the  pulse,  however,  is  rapid  and  compressible. 

In  our  experience  this  type  of  smallpox  occurs  most  commonly  in 
young  and  vigorous  persons.  It  is  rare  in  young  children  and  in  adults 
of  advanced  years.  The  majority  of  victims  are  included  between  the 
ages  of  fifteen  and  forty  years.  Un vaccinated  pregnant  women  seem 
particularly  susceptible  to  this  dreadful  form  of  the  disease. 

One  of  the  most  extraordinary  features  about  this  hopeless  malady 


TIIM   VA  filEri/'JS  OF  SMA  LIJ'OX  206 

is  tliat  i.li(;_j;i(Mil;il  <  nmlilioii  of  the  paticuL  j'ciuaiiiii  clear  almost  until 
the  last  mouKMit  oi  life.  There  may  he  delirium  or  stupor,  hut  usually 
the  hapless  vietim  faces  death  with  his  mind  unohscured  and  his  intellect 
unimpiu'nMl.  On  one  oecjision,  one  of  the  writers,  sfandin^  Ijy  fhe 
hedside  of  a  most  malignant  case  of  purj)uric  variola  mid  not  thinking 
that  the  patient  was  conscious,  remarked  to  the  residcmt  physician  that 
there  was  absolutely  no  ground  for  hope  in  this  case.  The  patient, 
although  his  face  was  of  livid  hue,  immediately  rose  in  bed,  and  in  a 
husky  voice  exclaimed,  with  surprise,  "J)octor,  do  you  m(;an  to  say 
that  I  cannot  get  well?"  In  less  than  twenty-four  hours  the  patient 
was  a  corpse. 

The  course  of  this  type  of  smallpox  is  extremely  rapid.  JJeatli  usually 
takes  place  fypn;i  tka-third-io. llie  sixth  day  of  the  eruption,  common! v 
as  a  result  ot  sudden  heart-taikire.  Instances  have  even  l)een  reconled 
in  which  the  patient  has  succumbed  during  the  initial  stage,  but  such 
cases  must  be  of  excessive  rarity.  No  more  terrible  disease  exists  than 
black  smallpox,  for  from  this  malady  there  is  no  hope  of  recovery. 

Variola  Pustulosa  Hemorrhagica. — Hemorrhagic  extravasation  into 
the  skin  may  develop  at  any  time  during  the  course  of  the  variolous 
exanthem.  Various  types  of  hemorrhagic  smallpox  may  exist,  inter- 
mediate between  variolous  purpura  and  the  pustular  hemorrhagic  form. 
Htemic  effusion  may  take  place  during  the  papular  stage  of  the  disease 
and  may  occur  in  the  papules  themselves  or  in  the  intervening  areas 
of  skin.  Or  the  cutaneous  hemorrhage  may  first  appear  during  the 
period  of  vesiculation.  In  this  case  the  vesicles,  instead  of  containing 
clear  serum,  fill  with  a  sanguinolent  fluid.  In  other  cases  the  extravasa- 
tion of  blood  may  be  delayed  until  the  pustular  stage  is  reached.  The 
later  the  hemorrhage  is  postponed,  the  more  conspicuous  are  the  variolous 
lesions.  The  earlier  it  develops,  the  more  will  the  true  smallpox  eruption 
be  suppressed.  The  amount  of  swelling  and  oedema  is  proportionate 
to  the  extent  and  development  of  the  smallpox  exanthem.  ^Vhen 
petechia?  and  ecchymoses  develop  early  the  skin  has  a  peculiar  livid 
appearance,  and  there  is  not  much  swelling.  Scattered  here  and  there 
between  the  flat,  poorly  formed  vesicles  are  seen  non-elevated,  pea- 
sized  or  larger,  bluish,  ecchymotic  spots. 

The  hemorrhagic  condition  of  the  pustules  may  be  limited  to  certain 
localities,  or  it  may  extend  over  the  entire  body.  Inspection  of  the  legs 
will  often  affard  the  first  evidence  of  this  mahgnant  tendencv.  During: 
the  papular  or  vesicular  stage  it  will  be  noted  that  some  of  the  lesions 
upon  the  lower  extremities  are  surrounded  by  a  lialo  of  the  tint  of 
dilute  claret  wine.  Ai  a  later  period  scattered  pustules  in  this  region 
will  be  seen  to  have  centres  of  the  color  of  indigo  blue.  Bv  degrees 
others  take  on  the  same  appearance  and  the  color  gradually  deepens, 
until  at  last  in  severe  cases  the  pustules  on  all  parts  of  the  body  become 
distinctly  hemorrhagic.  At  the  same  time  Mxid  spots  may  be  seen  upon 
the  mucous  membrane  of  the  mouth  and  fauces.  The  gums  are  spongy 
and  disposed  to  bleed.  Hemorrhages  occur  from  the  nose  and  internal 
mucous  surfaces,  as  in  purpuric  variola. 


206  SMALLPOX 

The  temperature  hovers  about  100°  F.,  but  rises  higher  in  the  event 
that  the  eruption  progresses  to  pustulation.  The  pulse  is  rapid  and  out 
of  proportion  in  frequency  to  the  moderate  febrile  movement.  As  in 
the  primary  hemorrhagic  type,  the  mind  commonly  remains  unclouded 
almost  until  the  end. 

This  form  of  hemorrhagic  smallpox  is  more  protracted  in  its  course 
than  variolous  purpura,  but  offers  scarcely  more  hope  for  the  patient. 
The  severity  of  the  prevailing  epidemic  influences  the  prognosis  to  a 
certain  extent.  In  the  malignant  epidemic  of  1871-72,  patients  present- 
ing even  mild  evidences  of  the  hemorrhagic  tendency  almost  invariably 
succumbed  to  the  disease.  At  other  times  we  have  seen  recovery  take 
place  in  a  few  cases,  but  only  among  those  in  whom  the  hemorrhagic 
condition  of  the  pustules  was  limited  to  a  small  number  of  lesions  and 
appeared  at  a  relatively  late  period  of  the  disease,  and  in  whom  hemor- 
rhages from  the  mucous  membrane  were  not  excessive  nor  long  continued. 

In  June,  1902,  a  woman,  aged  twenty-four  years,  was  admitted  to 
the  hospital  with  a  most  severe  smallpox.  She  had  never  been  success- 
fully vaccinated,  although  she  stated  the  attempt  had  been  made  six 
times.  On  admission  her  appearance  was  such  as  to  lead  us  to  regard 
her  case  as  practically  hopeless.  The  eruption  was  extremely  profuse 
and  of  a  dusky-red  color.  Upon  the  legs  some  of  the  vesicles  showed 
distinctly  bluish  centres.  On  raising  the  upper  lids  an  extensive  sub- 
conjunctival hemorrhage  was  visible  in  both  eyes.  The  patient  was 
expectorating  blood,  and  was  bleeding  from  the  uterus  and  kidneys. 
On  the  following  day  the  hemorrhagic  symptoms  began  to  subside  and 
the  variolous  lesions  to  develop  more  conspicuously.  The  hemorrhages 
gradually  ceased  and  the  pustules  filled  up  with  a  yellowish,  puriform 
material.  From  this  time  on  the  case  pursued  the,  usual  course  of  a 
severe  confluent  smallpox,  the  patient  finally  recovering  after  a  most 
desperate  illness.  Special  mention  is  made  of  this  case  inasmuch  as  it 
is  a  remarkable  exception  to  the  general  rule. 

We  have  never  known  recovery  to  result  where  all  or  nearly  all  of  the 
vesicles  assumed  the  hemorrhagic  character  at  an  early  stage,  and  where 
there  were  well-marked  epistaxis,  haematuria,  conjunctival  hemorrhage, 
and  bloody  stools,  together  with  rapid  and  feeble  pulse  and  the  peculiar 
livid,  purplish,  or  indigo  color  of  the  skin.  Pustular  hemorrhagic  small- 
pox is  more  apt  to  develop  in  aged  and  debilitated  subjects,  in  pregnant 
women,  and  in  those  addicted  to  the  free  use  of  alcohol. 

We  have  occasionally  seen  distinct  hemorrhage  into  the  pustules  in 
the  lower  extremities  of  individuals  who  had  a  smallpox  modified  by 
a  remote  vaccination.  Most  of  these  cases  pursued  the  course  of  a 
varioloid  and  did  not  appear,  to  any  great  extent,  to  be  unfavorably 
influenced  by  the  bloody  extravasation  into  the  lesions. 

The  prognosis  in  these  cases  depends  somewhat  upon  the  character 
of  the  prevailing  type  of  the  disease.  Modified  eruptions  associated 
with  hemorrhage  might  with  propriety  be  termed  hemorrhagic  varioloid. 

Exceptionally  Mild  Smallpox.^ — In  every  epidemic  of  variola  there 
are  seen  patients  who,  though  unprotected  by  previous  vaccination, 


TIIM  VAItlETII'^H,  OF  SMAfJ.POX 


207 


present  remarkably  mild  manif(!stalions  of  the-  disease.  'J'lie  exantliem 
in  such  cases  may  amount  to  merely  a  half-dozen  or  a  clfjzen  lesions,  or 
in  rare  instatices  there  may  be  even  a  complete  absence  of  the  eruption. 
The  mildness  of  the  constitutional  synijjtoins  and  the  paucity  of  the 
eruption  in  these  cases  may,  with  r(;ason,  be  attributed  to  a  certain 
degree  of  natural  insusceptibility  to  the  disease. 

,  We  desire  to  call  attention  to  the  fact  that  smallpox,  under  certain 
circumstances,  may  depart  from  its  usual  life  history  and,  during 
epidemic   prevalence,  exhibit  in   a  more  or  less   iiiiifonn    iiuniner  an 


Example  of  a  remarkably  mild  type  of  smallpox  which  has  been  prevailing  for  some  years  in 
various  sections  of  the  United  States.    Patient  unvaccinated. 

extraordinary  mildness.  Such  an  epidemic  has  been  prevailing  in 
various  sections  of  the  United  States  for  the  past  five  or  six  years.  It  is 
said  to  have  been  imported  into  this  country  from  Cuba,  "vvhere  it  had 
existed  during  the  Spanish-Cuban  war.  From  the  South  this  form 
of  smallpox  gradually  became  disseminated  throughout  the  Middle  and 
Western  States.  The  disease  was  recognized  as  contagious,  as  it  was 
seen  to  spread  from  one  person  to  another  and  from  town  to  town. 
But  wherever  it  appeared  it  was  observed  to  exiiibit  the  same  mild 
type,  rarely  resulting  in  death.  On  account  of  its  aberrant  symptom- 
atology there  was  considerable  diversity  of  opinion  among  physicians 


208  SMALLPOX 

as  to  the  nature  of  this  disease.  Many  regarded  it  as  chickenpox; 
others  contended  that  it  was  smallpox.  Still  others,  not  being  able  to 
reconcile  the  picture  with  the  symptomatology  of  either  of  these  two 
diseases,  regarded  the  new  form  as  impetigo  contagiosa,  or  as  a  cutaneous 
disease  of  a  new  and  strange  variety. 

During  the  years  1898,  1899,  and  1900  there  were  treated  in  the 
hospital  under  our  care  162  patients  suffering  from  this  mild  type  of 
smallpox.  Of  this  number  138  were  unvaccinated,  and  yet  not  a  single 
death  resulted;  12  of  the  patients  were  white  and  150  were  negroes. 
(The  disease  appeared  to  start  among  the  Southern  blacks,  but  later, 
in  other  portions  of  the  country,  the  whites  constituted  the  great  majority 
of  the  patients.) 

The  onset  of  this  type  of  smallpox  does  not  differ  greatly,  except  in 
degree,  from  that  commonly  seen  in  the  severer  forms  of  the  disease. 
According  to  information  obtained  from  many  of  the  patients  the 
entire  initial  illness  was  often  so  mild  that  they  were  not  obliged  to  remain 
constantly  in  bed;  some  even  stated  that  they  had  scarcely  been  ill  at 
all,  and  yet  on  close  interrogation  it  was  found  that  all  had  suffered  to 
some  degree  from  the  usual  symptoms.  In  a  few  patients  the  initial 
stage  was  marked  by  its  usual  severity. 

The  vast  majority  of  patients  would  not  remain  in  bed  after  the 
eruption  appeared.  They  preferred  to  don  their  clothes  and  indulge 
in  various  games.  It  was  a  novel  sight  to  see  these  unvaccinated  small- 
pox patients  engage  in  a  game  of  baseball  on  the  eighth  or  tenth  day 
of  the  eruption,  by  which  time  desiccation  was  often  well  advanced. 
Not  more  than  two  or  three  patients  during  this  epidemic  showed 
symptoms  which  were  at  all  serious.  In  some  of  the  mildest  cases  it 
was  impossible  to  count  as  many  as  a  dozen  pustules  upon  the  entire 
cutaneous  surface.  As  a  rule,  the  exanthem  was  discrete  and  the  lesions 
sparsely  distributed.  A  few  patients,  however,  exhibited  more  copious 
eruptions,  even  to  the  extent  of  producing  confluence  on  the  face.  In 
very  mild  cases  the  eruption  pursued  a  short,  abortive  course.  Even 
in  the  more  pronounced  cases  the  duration  of  the  disease  was  con- 
siderably abridged.  The  course  of  the  disease  was  identical  with  that 
seen  in  varioloid,  and  yet  in  the  vast  majority  of  the  patients  there  was 
no  known  modifying  influence  operating  such  as  results  from  vaccination 
or  a  previous  attack  of  the  disease. 

Why  smallpox  in  the  unvaccinated  should  present  itself  so  generally 
in  such  an  exceptionally  mild  form  is  a  problem  most  difficult  to  solve. 
It  has  been  suggested  that  this  form  of  variola  originated  in  Cuba  and 
that  smallpox  in  the  tropics  is  less  severe  than  in  cold  climates.  We 
are  not  sure  that  this  is  true,  but,  even  if  it  were,  there  is  no  reason  why 
the  disease  should  not  resume  its  old  and  familiar  form  when  transferred 
to  temperate  or  colder  regions.  It  has  furthermore  been  suggested  in 
explanation  of  the  mild  type  that  the  modification  is  due  to  hereditary 
vaccinal  influence.  That  this  is  not  true  is  evidenced  by  the  fact  that 
the  disease  in  the  South  prevailed  largely  among  negroes,  and  it  is  a 
notorious    fact    that    this    race    most    flagrantly    neglects    vaccination. 


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PLATE   XXIX. 


Same  Patient  as  in  Plate  XXVIII. 

Photograph  taken  48  hours  later  indicating  the  rapidity  of  the  stages  of 
desiccation  and  decrustation. 


THE   VAUIF/ril<:H  ()[<'  SMAhhI'OX  209 

Indeed,  wc  wore  able  to  ascertain  l)y  iii(|iiiry  tliiit  I  lie  parculs  of  many 
of  our  patients  had  never  been  vaccinated.  A^:i\u,  a  similar  milfl 
epidemic  occurred  in  the  days  of  Jcinicr,  before  there  would  fiave  been 
an  opportunity  for  an  hereditary  iulhicnce  to  become;  manifest.  Jenner 
in  1798  wrote: 

"About  seven  years  ago  a  species  of  smallpox  spread  through  many 
of  the  towns  and  villages  of  this  part  of  (Jloucesterslu're.  It  was 
of  so  mild  a  nature  that  a  fatal  instance  was  sc-arcely  ever  heard  of, 
and  consequently  so  little  dreaded  by  the  lower  orders  of  the  com- 
munity that  they  scrupled  not  to  hold  the  same  intercourse  with  each 
other  ks  if  no  infectious  disease  had  been  present  among  them.  I  never 
saw  nor  heard  of  an  instance  of  its  being  confluent.  The  most  accurate 
manner,  perhaps,  in  which  I  can  convey  an  idea  of  it  is,  by  saying  that 
had  fifty  individuals  been  taken  promiscuously  and  infected  by  exposure 
to  this  contagion  they  would  have  had  as  mild  and  light  a  disease  as 
if  they  had  been  inoculated  with  variolous  matter  in  the  usual  way. 
The  harmless  manner  in  which  it  showed  itself  coidd  not  arise  from 
any  peculiarity  either  in  the  season  or  the  weather,  for  I  watched  its 
progress  upward  of  a  year  without  perceiving  any  variation  in  its  general 
appearance.     I  consider  it,  then,  as  a  variety  of  the  smallpox." 

Sydenham  is  said  to  have  described  a  prototype  of  the  mild  variety 
of  smallpox  in  1771. 

Van  Swieten,  the  great  Dutch  physician  of  the  eighteenth  century, 
wrote  in  1759  as  follows: 

"The  primary  fever  is  often  little  more  than  a  febricula,  and  the 
pustules  seldom  exceed  more  than  from  one  to  two  hundred.  The  form 
is  so  mild  that  secondary  fever  is  not  manifested  and  constantly  is  want- 
ing, convalescence  coming  on  on  the  eighth  day  of  the  eruption." 

The  mildness  of  the  type  of  smallpox  under  discussion  may  be  compre- 
hended from  the  following  figures:  During  the  year  ending  June  30, 
1902,  there  were  in  the  United  States  55,857  cases  of  smallpox  w4th 
1852  deaths  (a  mortality  rate  of  3.31  per  cent.),  and  in  the  year  previous 
38,506  cases  and  689  deaths  (a  mortality  rate  of  1.79  per  cent.).  These 
figures  include  the  smallpox  in  certain  sections  of  the  country  where 
the  type  was  of  normal  severity. 

It  is  reasonable  to  presume  that  in  such  an  epidemic  the  causative 
germ  of  smallpox  has  become  attenuated  in  its  virulency,  as  a  result 
of  certain  unknown  influences.  By  no  other  method  of  reasoning  could 
we  account  for  the  singular  and  uniform  mildness  which  has  character- 
ized this  extensive  and  widespread  epidemic.  We  believe,  furthermore, 
that  the  infectivity  of  this  mild  variety  of  smallpox  is  considerably  less 
pronounced  than  that  of  classic  variola.  We  have  noted  that  this  type 
of  the  disease  has  frequently  failed  to  spread  where  there  appeared 
abundant  opportunity  for  its  diffusion. 

Varioloid  (Variola  Benigna;  Variola  Modificata ;  Modified  or  Miti- 
gated Smallpox). — The  term  varioloid,  from  an  etymological  point  of 
view,  would  indicate  a  disease  merely  bearing  a  resemblance  to  variola. 
The  impression  thus  conveyed  is,  of  course,  a  false  one,  for  varioloid 

14 


210         .  SMALLPOX 

is  true  smallpox  in  a  modified  form.  This  is  evident  from  the  fact  that 
the  infection  arising  from  this  milder  form  of  the  disease  gives  rise  to 
variola  vera  in  unprotected  persons.  Since  the  introduction  of  vac- 
cination varioloid  has  become  much  more  frequent  than  in  former 
times.  Indeed,,  in  well-vaccinated  communities  modified  smallpox  is 
apt  to  numerically  exceed  the  cases  of  ordinary  variola. 

It  is  well  known  that  the  immunity  conferred  by  vaccination,  although 
complete  at  first,  becomes  in  the  course  of  time  more  or  less  impaired 
in  the  vast  majority  of  individuals.  The  protective  influence  from  this 
procedure  diminishes  very  gradually  for  a  variable  period  of  time  and 
may  ultimately  become  entirely  extinguished.  It  is  readily  compre- 
hensible, therefore,. that  we  may  encounter  vaccinated  persons  in  whom, 
on  the  one  hand,  there  is  almost  complete  protection  against  smallpox, 
and,  on  the  other,  individuals  whose  susceptibility  to  smallpox  has  quite 
fully  returned.    TW  farmgrj.^jdien  they  co  smallpox,  will  exhibit 

the  mildest  sort  of  symptoms,  with  an  insignificant  eruption,  while  the" 
latter  may  develop  the  most  severe  confluent  or  even  hemorrhagic 
Tariola.  Between  these  two  extremes  one  may  encounter  almost  every 
possible  intermediate  grade.  It  should  be  stated,  however,  that  it  is 
exceptional  for  the  vaccinal  protection  to  be  completely  lost.  Usually 
a  modifying  influence  upon  the  course  of  the  disease  will  be  exerted, 
even  when  it  appears  at  the  outset  that  the  patient  is  going  to  suffer 
from  confluent  smallpox.  ^,The  vast  majority  of  vaccinated  persons 
who  contract  smallpox  have  the  Qpurse  of  the  resulting  disease  favorably 
influenced. 

We  class  as  varioloid  all  vaccinated  cases  in  which  the  eruption  is 
markedly  abridged  in  its  course  and  in  which  there  is  but  little  if  any 
secondary  rise  of  temperature.  To  be  sure,  cases  in  which  a  second 
attack  of  smallpox  is  favorably  influenced  by  an  antecedent  one  would 
also  deserve  this  designation.  We  regard  as  variola  all  un vaccinated 
cases  and  all  those  vaccinated  cases  in  which  the  eruption  pursues  its 
regular  course,  and  is  attended  with  secondary  or  suppurative  fever. 

There  are  certain  unprotected  individuals  who  possess  more  or  less 
natural  immunity  against  smallpox  and  in  whom  the  disease  is  mild 
and  of  short  duration.  Some  writers  would  include  these  cases  in  the 
category  of  varioloid,  but  we  prefer  to  regard  them  simply  as  mild 
forms  of  variola  vera. 

We  not  infrequently  meet  with  cases  of  smallpox  in  vaccinated  indi- 
viduals which  are  so  near  the  dividing  line  that  the  determination  of 
the  class  to  which  they  belong  must  be  postponed  until  the  suppura- 
tive stage  has  passed. 

Varioloid  cannot  always  be  distinguished  in  the  initial  stage  from 
variola  vera,  since  the  train  of  symptoms  may  be  the  same  and  of  equal 
severity  in  each.  In  many  cases,  however,  the  invasive  manifestations 
in  varioloid  are  extremely  mild  and  will  warrant  a  prediction  of  a 
sparse  exanthem.  Unmodified  smallpox  is  so  seldom  ushered  in  with 
mild  symptoms  that  the  likelihood  of  its  occurrence  after  shght  consti- 
tutional disturbance  is  remote.    It  is  important  to  remember,  however, 


Tlll<:   VAh'f/<JT//<:S  OF  SMAfJJ'OX 


211 


that  a  severe  initial  illness  docs  not  preelnde  llic  possibility  of  tlie  flevel- 
opinent  of  varioloid. 

The  duration  of  tlie  initial  stage  in  vaiioloid  is  suhjeft  to_j;onsidenjjLtl^ 
variation.  While  this  period  in  variola  liists  (jiiitc  nnii'orndy  thxefi^ilay^S' 
rri'varroloid  it  may  be  as  short  as  twenty-four  to  forty-ei^lit  hours^  or  as 
"Tong  as  four  or  five  days.  At  the  eonuneneenient  of  the  invasive  .stage 
'the  tenipcniiiire  rises  to  a  variable  height;  uj)on  the  outbreak  of  the 
eruption  it,  usually  drops  nither  suddenly  to  tiic;  jiorrnal  or  even  below 
this  point.  Ordinarily  no  subsc<jueiit  jisc  ricciiis  unless  eoniplieation.s 
(ievelot).     In  other  words,  the  average  case  of  varicjloifl  is  attended  \\  ith 


Pig.  -12 


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W.  C,  aged  tvveaty-uine  years.  ^  A  case  of  varioloid  showing  the  temperature  during  the  initial 
stage  ;  the  fever  began  to  decline  upon  the  appearance  of  the  eruption. 

^Jever  only  during  the  initial  stage.  With  the  subsidence  of  the  pyrexia 
there  is  a  general  abatement  of  all  of  the  systemic  symptoms.  The 
headache  and  backache  cease,  often  with  agreeable  promptness,  and 
the  patient  feels  quite  well  again.  In  every  large  epidemic  of  smallpox 
instances  are  noted  in  wdiich  artisans  and  workmen,  recovering  from 
the  mitial  stage  of  a  varioloid,  resume  their  daily  labors  unmindful  of 
the /'pimples,. which  have  broken  out"  on  them. _  Mild  cases  of  this 
character  are  a  fertile  source  of  spread  of  the  disease. 

The  initial  erythematous  exanthems,  more  particularly  the  morbilli- 
form type,  not  infrequauiiji^evclop  during  the  febrile  stage  of  varioloid. 
Indeed,  this^rodromal  rash,  not  unlike  measles  in  appearance,  is  so 


212  SMALLPOX 

commonly  followed  by  an  exceedingly  sparse  eruption  that  it  might 
"almost  be  regarded  when  present  as  the  forerunner  of  varioloidTjBiTr 
-if  ihe  rash  should  be  petechial  or  purpuric  in  character  it  is,  as  a  rule, 
an  indication  that  the  attack  will  be  severe. 

The  extent  of  the  eruption  varies  greatly  in  different  cases  of  varioloid. 
^  The  protection  may  be  almost  but  not  quite  complete,  and  the  patient 
may  pass  through  the  initial  stage  but  remain  free  of  eruption.  To 
this  niost  benignant  form  of  smallpox  the  term  variola  sine  exanthemate, 
or  variola  sine  variolis,  has  been  given.  A  case  reported  by  Curschmann 
well  illustrates  this  type  of  the  disease:  "During  a  severe  epidemic  of 
smallpox,  a  midwife,  aged  forty  years,  in  the  eighth  month  of  pregnancy, 
fell  sick  with  rigors,  followed  by  violent  fever,  headache,  pain  in  the 
back,  etc. — apparently  the  initial  stage  of  smallpox.  On  the  fourth 
day,  however,  she  was  free  from  fever,  and,  in  spite  of  the  most  careful 
examination,  exhibited  no  trace  of  the  expected  eruption.  Ten  days 
after  the  commencement  of  the  disease,  feeling  at  this  time  perfectly 
well,  she  gave  birth  to  a  child  covered  with  a  smallpox  eruption,  evidently 
just  appearing,  which  developed  still  further  and  in  three  days  terminated 
in  death  during  the  stage  of  suppuration." 

There  is  nothing  peculiar  about  the  eruption  of  varioloid  except  that 
it  is  milder  in  its  course,  of  shorter  duration  than  that  of  variola,  and 
exhibits  various  irregularities.  It  almost  always  appears  on  the  face 
and  rapidly  spreads  to  other  parts  of  the  body,  although  at  times  it 
makes  its  appearance  on  the  trunk  and  extremities  quite  as  early  as 
on  the  face.  The  lesions  do  not  develop  quite  as  regularly  as  in  un- 
modified smallpox,  it  being  not  unusual  to  find  some  pustules  larger 
and  farther  advanced  than  others.  The  eruption  may  be  limited  to  a 
very  few  lesions  on  the  face  and  hands,  or  it  may  assume  a  semiconfluent 
form,  and  also  invade  other  parts  of  the  body  to  a  considerable  extent. 
We  have  observed  several  undoubted  cases  in  which  but  a  single  lesion 
could  be  found  upon  the  entire  cutaneous  surface.  In  the  milder  forms 
the  lesions  do  not  pass  through  all  the  stages,  but  become  abortive  and 
dry  up  at  an  early  period.  In  the  severer  forms  the  eruption,  although 
confluent  or  semiconfluent,  pursues  a  distinctly  modified  course.  In 
such  cases  the  lesions  do  not  penetrate  into  the  deeper  layers  of  the 
skin,  but  remain  limited  to  the  epidermis.  Hence  the  course  of  erup- 
tion is  shorter,  the  process  of  suppuration  is  abridged,  and  the  lesions 
desiccate  early;  in  addition  the  crusts  are  rapidly  thrown  off  and  there 
is  little  or  no  scarring.  This  variety  of  smallpox  was  called  by  the 
earlier  writers  "confluent  superficial."  We  have  seen  vaccinated  patients 
,,.,.^-with  confluent  eruptions  which  in  the  begiiining  looked  most-fofmid^^~~~ 
,««jSyble,  and  dangerous;    but  the  magic  influence  of  the  vaccine  disease 

was  fortunately  there  to  convert  the  serious  malady  into  a  compara-'^ 
,.  tively  trifling  affection.  -.asiw 

More  frequently  the  eruption  of  varioloid  is  discrete  and  sparse,  but 
runs  the  same  mild  course.  ^The  papules  are  very  early  .cojiy^rted  into 
^j^esicles,  and  reach  the  .pustular  stage  on  the  third  or  fourth  day,  com- 
pleting their  evolution  from  the  fifth  to  the  seventh  day,  when  desiccation 


PLATE  XXXIV. 


Tubereulated  Elevations  (Variola  Verrucosa)  left  after 
the  Shedding  of  the  Crusts. 


Tim  VARIETIES  0/''  SMALLPOX  213 

begins.  The  pustules  are  frequently  acuminate  or  cfiiiiral,  (|iiite  unlike 
the  large,  heinisphorical  pustules  seen  in  unrnodififd  smallpox.  They 
dry  up  quickly,  forming  thin,  brownish  crusts,  which  fall  off  much 
sooner  than  in  the  ordinary  form  of  the  disease.  After  decrustation 
reddish  stains,  later  becoming  brown,  may  be  left,  but  these  are  not  as 
persistent  as  in  variola  vera.  Owing  to  the  superficial  character  of  the 
skin  involvement  in  varioloid,  most  of  the  patients  escape  without  any 
permanent  scarring. 

When  the  modification  of  the  eruption  is  still  greater,  it  is  not  unusual 
to  find  that  the  lesions  develop  into  large,  solid,  conical  papules,  having 
at  their  apices  small  vesicles  which  rapidly  desiccate  and  form  thin 
crusts.  After  the  crusts  have  fallen  off  the  lesions  remain  tuberculated 
for  some  time.  Viewing  a  patient  with  this  condition  from  a  little 
distance  it  is  often  difficult  to  say  whether  the  eruption  is  just  beginning 
or  terminating.  Sometimes  these  tubercles  present  the  appearance  of 
warty  excrescences;  to  this  form  of  the  eruption  the  name  variola 
verrucosa,  or  wart  pox,  has  been  given.  This  modification  of  the  smallpox 
eruption  is  seen  usually  upon  the  face.  In  the  course  of  time  the  eleva- 
tions flatten  down  and  disappear,  as  a  rule,  without  leaving  scars. 
Another  somewhat  common  form  of  the  eruption  is  that  known  as 
variola  miliaris;  in  this  variety  the  majority  of  the  vesicles  are  very 
small,  not  larger  than  millet  seeds;  without  progressing  further  they 
turn  yellow,  desiccate  and  disappear.  Not  rarely  a  few  tolerably  well 
developed  pustules  are  found  mixed  with  these  smaller  lesions. 

Variola  corymhosa  is  a  designation  applied  to  those  eruptions  which 
exhibit  grouping  of  rather  flat  pustules  in  the  form  of  corymbs  or 
clusters.  It  is  alleged  by  some  writers  that  the  mortality  rate  is  par- 
ticularly high  in  cases  showing  this  character  of  eruption. 

The  contents  of  abortive  vesicles  and  pustules  frequently  desiccate 
without  rupturing,  producing  hard,  horny,  convex,  shining,  reddish- 
brown  crusts.  This  form  is  designated  variola  cornea,  or  horii  pox. 
The  reddish-brown,  horny  crusts  are  quite  characteristic  of  smallpox. 
They  are  particularly  common  in  varioloid,  and  often  materially  aid 
one  in  the  diagnosis  of  doubtful  cases.  They  are  of  distinct  value  in 
cases  which  are  seen  for  the  first  time  at  a  late  stage,  when  the  original 
appearance  of  the  eruption  is  altered.  The  horny  crusts  are  seen  most 
frequently  on  the  hands  and  forearms,  but  may  also  be  noticed  at  times 
on  the  face. 

In  the  form  of  the  eruption  termed  variola  siliqvosa,  there  is  a  retro- 
gression of  the  pustules  with  absorption  of  the  contents  and  the  pro- 
duction of  epidermal  cavities  filled  with  air.  In  addition  to  the  above 
irregular  forms  of  the  smallpox  eruption,  writers  have  described  other 
varieties,  such  as  variola  conica,  crystallina,  empliysematica,  fimbriata, 
lymphatica,  pemphigosa,  pustularis,  rosea,  morhillosa,  carhunculosa, 
globulosa,  etc. 

These  various  designations  do  not  indicate  separate  varieties  of  the 
disease,  but  merely  different  appearances  produced  by  more  or  less 
trifling  changes  in  the  lesions. 


214  SMALLPOX 

The  mucous  membrane  of  the  mouth  and  upper  air  passages  is 
usually  affected  in  varioloid,  but  much  less  severely  than  in  unmodified 
smallpox.  The  various  complications  involving  the  skin,  eye,  and 
other  organs  may  occur  in  varioloid,  although  they  are  decidedly  less 
frequent  and  less  severe  in  this  form  of  the  disease.  In  rare  instances 
grave  affections  of  the  brain  and  spinal  cord  may  complicate  mild  cases 
of  smallpox;  to  this  more  extended  reference  will  be  made  in  considering 
the  complications  of  variola. 

Inoculated  Smallpox. — Although  the  practice  of  inoculation  of  small- 
pox is  completely  obsolete  and  prohibited  in  most  countries  by  statu- 
tory legislation  at  the  present  time,  it  is  of  interest  to  know  the  clinical 
appearances  produced  by  it.  Not  having  had  any  practical  experience 
with  this  form  of  the  disease,  we  prefer  to  present  the  description 
given  by  Gregory: 

"  Inoculation  is  performed  by  introducing  into  the  arm  at  the  insertion 
of  the  deltoid,  by  means  of  a  lancet,  a  minute  portion  of  variolous 
matter.  The  thin  lymph  of  a  fifth-day  vesicle  is  to  be  preferred  to  the 
well-concocted  purulent  matter  of  the  eighth-day  matter,  but  both 
are  efficient.  One  incision  only  is  to  be  made.  A  minute  orange- 
colored  spot  is  perceptible,  by  aid  of  the  microscope,  on  the  second  day; 
on  the  third  or  fourth  day  a  sensation  of  pricking  is  observed  in  the 
part.  The  punctured  point  is  hard,  and  a  minute'  vesicle,  whose  centre 
is  depressed,  may  be  observed  surmounting  an  inflamed  base.  On  the 
fifth  day  the  vesicle  is  well  developed  and  the  areola  commences.  On 
the  sixth  day  the  patient  feels  stiffness  in  the  axilla,  with  pain.  The 
inoculated  part  has  become  a  hard  and  inflamed  phlegmon.  The 
subjacent  cellular  membrane  has  become  involved  in  the  inflammatory 
action.  On  the  evening  of  the  seventh  day  or  early  on  the  eighth  day, 
rigors,  headache,  a  fit  of  syncope,  vomiting,  an  offensive  state  of  the 
breath,  alternate  heats  and  chills,  languor,  lassitude,  or  in  the  child 
an  epileptic  paroxysm,  announce  the  setting  in  of  fever.  The  constitu- 
tion has  taken  alarm  and  sympathizes  with  the  progress  of  the  local 
disorder. 

"  On  the  appearance  of  the  febrile  symptoms  the  inflammation  of  the 
arm  spreads  rapidly.  An  areola  of  irregular  shape  is  soon  completed, 
which  displays  within  it  minute  confluent  vesicles.  On  the  tenth  day 
the  arm  is  hard,  tense,  shining,  and  very  red.  The  pustules  discharge 
copiously  and  ulceration  has  evidently  penetrated  the  whole  depth  of 
the  corium. 

"  On  the  eighth  day  spots  of  variolous  eruption  show  themselves  in 
various  and  often  most  distant  parts  of  the  body.  In  a  very  large 
proportion  of  cases  the  eruption  is  distinct  and  moderate.  Two  hundred 
vesicles  are  counted  a  full  crop.  Sometimes  not  more  than  two  or 
three  papulae  can  be  discovered,  which  perhaps  shrivel  and  dry  up 
without  going  through  the  regular  process  of  maturation.  At  other 
times  the  eruption  is  full  and  semiconfluent,  passing  through  all  of  the 
stages  of  maturation,  scabbing,  and  cicatrization.  Between  these 
extremes  every  possible  variety  may  be  observed.    The  truly  confluent 


THE  VARIETIES  OF  SMALLPOX  215 

eruption  with  affection  of  the  mucous  rnem})rane  is  rare.     Secondary 
fever,  tluM-cfore,  is  not  common,  at  least  in  any  intensity. 

"Tlie  rules  laid  down  for  the  safe  conduct  of  inoculation  were  [jriiif:i- 
pally  the  following:  It  should  be  performed  exclusively  in  persons  free 
from  actual  bodily  disease,  and  neither  plethoric  nor  scrofuhjus.  It 
may  be  safely  practised  at  all  ages,  beginning  at  the  third  month.  It 
is  improper  "to  inoculate  during  pregnancy,  on  account  of  danger  to 
the  child  in  utero.  Laxative  medicine,  a  moderate  diet,  abstinence 
from  all  fermented  and  spirituous  liquors,  cool  chambers,  gentle  exercise 
in  the  open  air,  hght  clothing— ^all  contribute  in  their  several  degrees 
to  the  successful  result. 

"The  influence  of  inoculation  in  lessening  the  mortality  of  smallpox 
was  something  quite  extraordinary  and  scarcely  credible.  With  ordinary 
precaution  in  the  choice  and  preparation  of  subjects,  not  more  than  1 
in  500  cases  will  terminate  unfavorably.  Had  not  the  discovery 
of  Jenner  interfered  to  interrupt  its  extension  and  improvement,  inocula- 
tion would  have  continued  to  this  day,  increasing  yearly  in  popularity. 
It  cannot  be  doubted  that  improvements  in  medical  science  generally 
would  have  shed  additional  lustre  on  this  practice." 

By  no  means  all  of  the  older  writers  were  so  favorably  disposed 
toward  inoculation  as  Gregory.  Considerable  diversity  of  opinion 
existed  as  to  the  mortality  rate  after  this  procedure.  Dr.  Jurin,  after 
examining  the  London  bills  of  mortality  for  forty-two  years,  concluded 
that  1  among  every  50  persons  inoculated  died.  Apart  from  the 
danger  to  the  individual,  great  disadvantage  arose  from  the  continuance 
of  the  disease  by  inoculation  and  the  establishment  of  numerous  foci 
of  contagion  from  which  smallpox  could  be  spontaneously  disseminated. 
It  is  alleged  that  the  annual  mortality  from  this  disease  was  increased 
by  the  practice  of  this  procedure. 

Smallpox  in  the  PregnantWoman.— The  functions  of  the  uterus  are 
disturbed  with  striking  frequency  during  the  course  of  smallpox.  The 
menses  quite  uniformly  appear  out  of  their  normal  course,  and  m 
pregnant  women  abortion  or  premature  birth  is  an  accident  of  common 
occurrence,  and  one  that  adds  greatly  to  the  danger  of  the  disease. 
Although  the  premature  advent  of  menstruation  and  even  the  occurrence 
of  abortion  are  not  uncommon  events  in  many  other  infectious  diseases, 
their  occurrence  in  smallpox  is  so  extremely  frequent  as  to  suggest  a 
direct  relationship  with  the  variolous  process.  It  is  probable  that 
abortion  is  the  result  of  the  uterine  hemorrhage  which  is  so  commonly 
excited  during  an  attack  of  smallpox.  In  some  cases  it  may  be  due 
to  the  death  of  the  foetus  which  is  suffering  from  an  intrauterine  variola. 
The  symptomatology  and  course  of  smallpox  are  often  markedly 
influenced  by  the  pregnant  state.  The  gravity  of  the  disease  is  con- 
siderably augmented  as  a  result  of  the  coexistence  of  this  condition. 
Of  113  'cases  of  smallpox  in  pregnant  women  treated  under  our  care, 
35  died,  constituting  a  mortality  rate  of  about  31  per  cent.  In  unvac- 
cinated  women  the  death  rate  has  been  truly  frightful,  twenty  dying 
out  of  a  total  of  twenty-seven  such  cases,  giving  a  mortality  rate  of 


216  SMALLPOX 


over  74  per  cent.     Of  85  women  vaccinated  at  some  previous  remote 
period,  14  died,  the  mortality  rate  being  about  16  per  cent. 


Died. 

Mort.  rate. 

85 

14 

16% 

27 

20 

74% 

1 

1 

Smallpox  in  pregnant  women  (vaccinated)        .... 
"  "  "       (unvaccinated)    .... 

"  "  "       (vaccine  condition  unknown) . 

Total        ....    113  35  30  % 

If  abortion  occurs  during  the  initial  stage  the  disease  is  apt  to  assume 
the  form  of  purpura  variolosa,  in  which  case  death  is  practically  inevit- 
able. Not  every  case  in  which  abortion  or  premature  birth  occurs  in 
the  earlier  stages  of  the  disease  takes  on  this  malignant  form.  In 
attacks  which  are  considerably  modified  by  previous  vaccination,  the 
smallpox  process  is,  of  course,  not  so  seriously  affected  by  the  occur- 
rence of  this  accident.  Even  in  cases  of  true  variola,  when  the  loss  of 
blood  is  not  very  great — which  is  rarely  the  case — the  variolous  process 
may  pursue  its  regular  course  and  progress  to  a  favorable  termination. 
In  but  5  cases  out  of  31  did  recovery  occur,  when  abortion  took  place 
before  the  tenth  day  of  the  eruption. 

For  facts  in  support  of  what  has  been  said  relative  to  smallpox  exciting 
abortion  when  the  pregnant  are  attacked,  and  to  the  increased  mortality 
from  the  disease  when  this  complication  arises,  the  reader  is  referred 
to  the  appended  table. 

On  examination  of  the  table  it  will  be  seen  that  out  of  113  cases  of 
smallpox,  including  both  variola  and  varioloid,  occurring  in  pregnant 
women,  65,  or  58.4  per  cent.,  suffered  from  abortion  or  premature 
delivery.  Of  the  remaining  48^  8  died  without  aborting,  9  recovered 
without  abortion  occurring  and  were  delivered  at  term,  and  31  were 
discharged  still  carrying  the  foetus,  but  were  not  heard  from  after 
leaving  the  hospital.  Of  the  65  cases  (including  variola  and  varioloid) 
in  which  abortion  or  premature  birth  occurred,  26,  or  40  per  cent.,  died. 

Abortion  occurs  in  variola  more  frequently  than  in  varioloid,  though 
the  difference  is  not  as  pronounced  as  one  might  expect.  The  table 
shows  that  of  our  49  cases  of  variola,  35,  or  71.42  per  cent.,  miscarried, 
and  out  of  63  cases  of  varioloid,  31,  or  49.2  per  cent.,  miscarried.  It 
is  probable  that  some  of  the  patients  who  left  the  hospital  carrying  the 
foetus  aborted  before  the  completion  of  the  period  of  gestation,  for  we 
have  observed  this  to  occur  not  infrequently. 

When  miscarriage  occurs  in  variola  it  proves,  of  course,  a  much  more 
serious  complication  than  when  it  occurs  in  varioloid.  By  reference 
to  the  table  we  find,  out  of  35  cases  of  variola  thus  complicated,  26,  or 
74.28  per  cent.,  died;  while  among  31  cases  of  varioloid  in  which  the 
complication  occurred  but  1  died,  and  this  death  resulted  from  puerperal 
peritonitis. 

The  period  at  which  miscarriage  most  frequently  takes  place  is  during 
the  second,  or  eruptive  stage  of  the  disease.  It  not  only  occurs  during 
the  course  of  the  disease,  but  frequently  during  convalescence,  and  in 
many  instances  even  several  weeks  after  complete  restoration  to  health. 

Miscarriages  prove  the  more  serious  the  earlier  they  occur  in  the 


77//';  VA  h'ff<:Tir<JS  of  SMy\  llpox  2 1 7 

course  of  smallpox.     This  is  shown  in  the  accornpunyin^  lahlc,  wliich 
includes  cases  of  variola  and  varioloid: 

Day  of  the  Ehui'tion  on  which  MiscAiuuAfiK  Occijrkku,  with 

CORKKHI'ONDINfi    MoilTALITY. 

CufleH.         DeatiiB. 

Initial  stage ■!  2 

On  or  before  the  fifth  day  of  eruption '•'•O  17 

From  fiftli  to  tvvcntietli  day Ifi  « 

Subsequent  to  twentieth  day H  0 

Miscarriage  occurs  doubtless  much  more  often  during  the  iiiili;il 
stage  of  the  disease,  particularly  during  epidemics,  than  the  table  would 
lead  us  to  believe.  In  such  cases  death  usually  follows  so  speedily  that 
the  true  nature  of  the  disease  is  often  overlooked,  or,  if  recognized,  the 
critical  condition  of  the  patient  forbids  removal  to  the  hospital;  hence 
the  table  shows  a  relatively  small  number  of  miscarriages  occurring  at 
this  stage  of  the  disease. 

The  gravity  of  smallpox  in  pregnant  women  appears  to  vary  con- 
siderably in  different  epidemics.  We  have  had  the  opportunity  of 
observing  these  cases  in  three  rather  extensive  periods  of  smallpox 
prevalence.  The  following  table  will  indicate  the  comparative  mortality 
rates  of  pregnancy  and  abortion  complicating  smallpox  during  the 
three  epidemics: 

Number.  Deaths. 

1871-72.   Pregnancies 46  14  or  30.43  % 

Abortions  and  premature  births         .       .       .27  10  or  37. 00" 

Variola 10  10  or  100     " 

Varioloid 13  

1881-82.   Pregnancies 31  16  or  51.61  % 

Abortions  and  premature  births        .       .       .19  13  or  68.42  " 

Variola 15  13  or  86.66" 

Varioloid 4  1  or  25.00  " 

1901-02.  Pregnancies 36  5  or  13.88  " 

Abortions  and  premature  births        ...    20  3  or  15.00  " 

Variola 6  3  or  50.00  " 

Varioloid 14  

The  above  tables  show  that  the  mortality  rate  in  pregnant  smallpox 
women  in  1871-72  was  30.43  per  cent.;  in  1881-82,  51.61  per  cent., 
and  in  1901-02,  13.8  per  cent.  Of  those  that  aborted  the  mortality 
rate  in  1871-72  was  37  per  cent.;  in  1881-82,  68.42  per  cent.,  and  in 
190.1-02  only  15  per  cent.^  t_ 

1  Since  compiling  the  above  figures,  eight  pregnant  women  with  smallpox  have  been  admitted  to 
the  hospital.    Of  this  number  five  aborted,  one  of  whom  died. 


218 


SMALLPOX 
Smallpox  in  PregnAkt  Women. 


No. 

Age 

1 

23 

2 

27 

3 

35 

4 

21 

5 

32 

6 

24 

7 

30 

8 

26 

9 

22 

10 

35 

11 

15 

12 

23 

13 

22 

14 

18 

15 

21 

16 

29 

17 

30 

18 

30 

19 

27 

20 

27 

21 

26 

22 

32 

23 

20 

n 

17 

25 

24 

26 

19 

27 

26 

28 

22 

29 

SO 

30 

20 

31 

25 

32 

25 

33 

45 

34 

19 

Character 

of 
disease. 


Variola 
(confluent), 
Variola. 


Varioloid. 

Variola. 

Varioloid 
(mild). 
Variola 
(confluent). 

Variola. 

Varioloid. 

Variola. 

Varioloid. 

Variola. 

Varioloid. 


Varioloid 

(mild). 

Varioloid. 


Varioloid 
(mild). 

Variola. 


Varioloid. 
Variola. 

Variola 
(confluent), 

Varioloid. 

Variola. 


Variola 
(confluent). 
Variola. 


Varioloid 
(mild). 
Variola. 


Varioloid 
(mild). 
Variola. 

Varioloid. 

Variola. 

Variola 
(confluent). 
Varioloid 

(mild). 
Varioloid. 


Whether  vac- 
cinated, and  if 
so,  character 
of  cicatrix. 


Poor  scar. 
Good     " 

Fair       " 
Poor      " 
10  poor  scars. 
1  fair  scar. 

1  poor  " 
1  fair   " 
Not  vaccinated 

1  poor  scar. 
Not  vaccinated 
Good  scar. 


Poor 

Good 

Poor 

Fair 
Poor 

Not  vaccinated 

4  good  scars. 
Not  vaccinated 

Fair  scar. 

5  good  scars. 
Fair  scar. 

Poor      " 
3  poor  scars. 
Fair  scar. 
Good     " 

6  poor  scars. 
Fair  scar. 
Poor      " 


Month  of 
pregn'cy 

when 
attacked. 


4 
3 

3 

2 
5 
8 

5)^ 
3 

3 

3 

2 

814 

3 

5 


5% 

7 
3 

7  or  8 

8 
6 

4 
3 

6 
5 

3 

5K 
8 

4 
6 
6 


Stage  of  disease 
at  which  abor- 
tion occurred. 


4th  day  of  erup- 
tion. 

18th  day  of  erup- 
tion. 
3d  week. 

After  leaving 

hospital, 
let  day  of  initial 

fever. 


5  weeks  after 
leaving  hosp. 

1st  day  of  erup- 
tion. 


10  days  after 
leaving  hosp. 

26th  day  of  erup- 
tion. 

9th  day  of  erup- 
tion. 


Delivered  at 
early  stage  of 
eruption, 

2d  day  of  erup- 
tion. 


1st  day  of  erup- 
tion. 

3d  day  of  erup- 
tion. 


6  weeks  after 
leaving  hosp. 


1  month  after 
leaving  hosp. 

3d  day  of  erup- 
tion. 

2d  day  of  erup- 
tion. 

4th  day  of  erup- 
tion. 

1st  day  of  erup- 
tion. 


5th  day  of  erup- 
tion. 


Result. 


Recov- 
ered. 
Died 

5th  day 

of  erup. 

Recov- 
ered. 


Died 
3d  day 
of  erup. 
Recov- 
ered. 


Died 
6th  day 
of  erup. 
Recov- 
ered. 
Died 
9th  day. 
Recov- 
ered. 


Died 
5th  day 
of  erup. 
Recov- 
ered. 

Died 
3d  day 
of  erup. 
Recov- 
ered. 
Died 
7th  day 
of  erup. 

Died 
11th  d'y 
of  erup. 
Recov- 
ered. 
Died 
7th  day 
of  erup. 
Recov- 
ered. 
Died 
27th  d'y 
of  erup. 
Recov- 
ered. 
Died 
6th  day 
of  erup. 
Recov- 
ered. 


Remarks. 


Deliveied  at  term  ;  child 
healthy ;  was  success- 
fully vaccinated. 


Ran  away  from  hospital, 
and   subsequently 
aborted. 


Delivered  at  term. 


Delivered  at  term. 

Patient  said  to  have  been 
pregnant,  but  abortion 
did  not  occur. 

The  foetus  presented  a 
few  red  spots  evidently 
the  result  of  a  slight 
vesicular  eruption. 


Child  lived  one  or  two 
days ;  died  of  debility. 

Delivered  at  term. 

Died  while  in  the  act  of 
abortion. 

Aborted  six  weeks  after 
leaving  hospital. 

Died  of  pleurisy,  with- 
out aborting. 

Aborted  one  month  after 
leaving  ho.ipital. 


Infant  died  of  debility. 
Delivered  at  term. 


Delivered  at  term. 


riiic  vAHJi'7ni<:H  of  smal/j'ox 


210 


No. 

Age 
26 

Character 

of 
dlnease. 

Whether  vac- 
cinated, and  if 
80,  character 
of  cicatrix. 

Month  of 
prcgn'cy 

when 
attacked. 

7K 

Si  age  of  disease! 
at  which  abor- 
tion occurred. 

KcKlilt, 

Died 

RctiiurkK, 

35 

Variola. 

Not  vaccinated 

Ist  day  of  erufi- 

tion. 

4th  day 
of  erup. 

36 

18 

Varioloid. 

3  fair  scars. 

^A 

Recov- 
ered. 

37 

26 

Variola. 

Unknown. 

8 

Early  stage  of 
eruption. 

Died. 

Died  on  way  to  hofpital  ; 
infant  died  of  debility. 

3S 

41 

Varioloid. 

2  good  scars. 

8 

3d  day  of  erup- 
tion. 

Recov- 
ered. 

Infant  died  of  debility. 

39 

28 

•  ♦ 

Fair  scar. 

4X 

Delivercfl  at  term  ■  child 

successlnlly  vaccinat'd. 

40 

30 

*' 

2  fair  scars. 

G 

(* 

Delivered  at  term  ;  child 
successfully  vaccinat'd. 

41 

25 

" 

Good  scar. 

3 

1st  day  of  erup- 
tion. 
5th  day  of  erup- 

" 

42 

20 

Variola. 

Poor      " 

G'A 

Died 

Infant    lived    about    24 

tion. 

Hh  day 
of  erup. 

hours. 

43 

22 

Varioloid. 

Good     " 

5 

Recov- 

Delivered at  term  :  child 
died  when  two  months 

ered. 

old,  without  being  vac- 

cinated. 

44 

28 

" 

4  good  scars. 

6 

tt 

Delivered  at  term  :  child 
successfuly  vaccinated. 

45 

21 

8    " 

5 

During  matura- 
tion. 

** 

46 

25 

Varioloid 
(mild). 

3  fair     " 

6 

" 

47 

21 

Variola 
(confluent). 

Not  vaccinated 

SA 

" 

4S 

32 

Variola. 

1  poor  mark. 

5 

Aborted  12th  day 
ot  eruption. 

Died. 

49 

30 

Varioloid. 

1    " 

8 

Aborted  2d  day 
of  eruption. 

Recov- 
ered. 

Child  successfully  vacci- 
nated; died  later  of  de- 

50 

34 

Variola. 

Not  vaccinated 

5 

Died  without  ab- 
orting, 6th  dav. 

Died. 

bility. 

51 

26 

Varioloid. 

3  fair  scars. 

Aborted  3d  day 
of  eruption. 

Died  of  puerperal  peri- 
tonitis. 

52 

16 

1  good  scar. 

7 

Dischartied 
carrying  fcEtus. 

Recov- 
ered. 

53 

29 

6  fair  and  2 
poor  scars. 

3 

25lh  day  of  erup- 
tion. 

'* 

54 

22 

2  good  scars. 

2 

Discharged 
carrying  icetus. 

" 

Delivered  at  term. 

55 

22 

Variola 
(hemor- 
rhagic). 

Not  vaccinated 

C  weeks 

Aborted  before 
death. 

Died. 

56 

25 

Varioloid. 

2  good  scars. 

6 

Discharged 
carrying  fcetus. 

Recov- 
ered. 

57 

36 

Variola 
(hemor- 
rhagic). 

1  poor  scar. 

7 

1st  day  of  erup- 
tion 

Died 
7th  day 
of  erup. 

58 

40 

Varioloid 
(mild). 

2  poor  scars. 

6 

Discharged 
carrying  fffitus. 

Recov- 
ered. 

59 

38 

Varioloid. 

1  fair  scar. 

2 

Discharged 
carrying  fretus. 

60 

19 

Variola. 

Not  vaccinated 

7 

Aborted  before 
death,  7th  day. 

Died. 

61 

22 

5 

Day  before  erup- 
tion. 

Died 
6th  day 
of  erup". 
Recov- 

62 

33 

Varioloid. 

2  good  scars. 

7 

Discharged 

carrying  foetus. 

ered. 

63 

23 

Variola 
(confluent). 

Not  vaccinated 

5 

Aborted  15th  day 
of  eruption. 

Died 
15th  dv. 

64 

19 

Variola 
(confluent). 

" 

3 

Aborted  11th  day 
of  eruption. 

Died 
nth  dv. 

65 

18 

Variola 
(confluent). 

3 

Discharged 
carrying  foetus. 

Recov- 
ered. 

Aborted  later. 

66 

38 

Varioloid 
(mild). 

2  good  and  2 
lair  scare. 

6 

Discharged 
carrying  fcetus. 

67 

29 

Varioloid. 

1  good  scar. 

eji 

Aborted  before 
eruption. 

" 

68 

24 

Variola 
(confluent). 

Not  vaccinated 

3 

Aborted  11th  day 
of  eruption. 

Died 
11th  dv. 

69 

Variola 

"          " 

8 

Aborted  1st  day 

Died" 

Infant  succewfully  vac- 

(confluent). 

of  eruption. 

cinated  ;  developed  14 

TO 

24 

Variola 
(hemor- 
rhagic). 

4 

Aborted  Sth  day 
of  eruption. 

Died. 

papules;  died  of  de- 
bihty. 

220 


SMALLPOX 


No. 

71 

72 
73 

74 
75 
76 

77 
78 


Age 

23 
27 
30 

30 
19 
30 
33 
25 


97 


100 


Character 

of 
disease. 


Whether  vac- 
cinated, and  if 
so,  character 
of  cicatrix. 


Varioloid. 
Variola. 

Variola 
(hemor- 
rhagic). 

Variola. 


Varioloid. 

Variola 

(confluent). 

Variola 
(hemor- 
rhagic). 

Variola 
(confluent). 


Variola 
(semicon- 

fluent). 
Varioloid 

(mild). 
Varioloid. 


Variola 
(hemor- 
rhagic). 

Varioloid. 


Variola' 
(confluent) 
Varioloid. 


Variola 

(confluent), 

Varioloid. 


Variola 

(confluent). 

Varioloid. 

Variola 
(confluent). 


Varioloid. 


Montlvof 
pregn'cy 

when 
attacked. 


1  fair  scar. 
1    "       " 

3  poor  scars. 
Not  vaccinated 
3  good  scars. 
Not  vaccinated 
1  poor  scar. 

Not  vaccinated 


1  good  scar. 

2  poor  scars. 
1  fair  mark. 
1  fair  scar. 
Not  vaccinated 

1  fair  scar. 

2  good  scars. 


Not  vaccinated 

Vac.  10  days 
before  erup. 

Vaccinated  be 
fore  eruption. 

1  fair  scar. 

Not  vaccinated 

Vaccinated  be 
fore  eruption. 


1  good  and  1 
poor  scar. 

2  good  scars. 
Not  vaccinated 

1  good  scar. 
Not  vaccinated 


1  fair  scar. 
1  poor    " 


5>^ 

4 

5 

5 
1 

8 
4 


3 

8K 


Stage  of  disease 
at  which  abor- 
tion occurred . 


Discharged 

carrying  foetus. 
Aborted  19th  day 

of  eruption. 
Died  7th  day 

without  abort. 

Aborted  7th  day 

of  eruption. 
Aborted  1st  day 

of  eruption. 
Discharged 

carrying  fcetus. 
Aborted  6th  day 

of  eruption. 
Aborted  1st  day 

of  eruption. 


Died  without 
aborting. 


Discharged 
carrying  fcetus. 

Aborted  6th  day 

of  eruption. 
Aborted  4  th  day 

of  eruption. 
Aborted  23d  day 

of  eruption. 
Discharged 

carrying  foetus. 
Died  without 

aborting. 

Delivered   21st 
day  of  eruption. 

Aborted  1st  day 
of  eruption. 


Discharged 

carrying  foetus. 
Aborted  17th  day 

of  eruption. 
Aborted  18th  day 

of  eruption. 
Discharged 

carrying  foetus. 
Discharged 

carrying  foetus. 
Aborted  33d  day 

of  eruption. 


Delivered  2  days 
before  eruption. 


Discharged 
carrying  foetus. 

Aborted  just  be- 
fore death  3d 
day. 

Discharged 
carrying  foetus. 

Delivered  on  9th 
day. 


Discharged 

carrying  fcetus. 
Discharged 

carrying  foetus. 


Result. 

Remarks. 

Recov- 

ered. 

" 

Foetus  had  well-marked 

variolous  vesicles  scat- 

Died. 

tered  over  body. 

Died 

7th  day. 

Died 

1st  day. 

Recov- 

ered. 

Died 

6th  day. 

Died 

Infant  infected  in  utero, 

4th  day. 

exhibiting  eruption  on 

9th  day  of  life  ;  died  on 

14h  day. 

Died 

Ceesarean    section    per- 

8th day. 

formed  immediately 

after  death,  but  infant 

found  dead. 

Recov- 

Delivered at  term. 

ered. 

<. 

Infant   vaccinated   at 

birth  ;    vaccination 

" 

took;  later  contracted 

,. 

varioloid  and  died. 

" 

Delivered  at  term. 

Died. 

Post-mortem  Csesarean 

section ;  foetus  dead. 

Recov- 

Child vaccinated  three 

ered. 

times,  but  without  suc- 

cess   remained  well. 

" 

Child  was   successfully 

vaccinated,    but    soon 

developed  smallpox 

eruption  and  died  ;  in- 

fection in  utero. 

.< 

Delivered  at  term. 

*' 

Delivered  at  term. 

" 

Delivered  at  term. 

« 

Child  at  birth  was  dead 

and  covered  with  a  dis- 

crete smallpox  in  the 

pustular  stage. 

" 

Baby  vaccinated,  but 

without  success ;  devel- 

oped   smallpox    erup- 

tion and  died. 

" 

Delivered  at  term. 

Died. 

Recov- 

ered. 

" 

Child   was   successfully 

vaccinated  ;   smallpox 

appeared  on  7th   day. 

and  child  died ;  infec- 

tion in  utero. 

" 

Delivered  at  term. 

** 

Delivered  at  term. 

THE  VARIETII'JS  f)/''  SMALLPOX 


22J 


No. 

Age 
23 

Character 

ot 
disease. 

Variola. 

Whether  vac- 
cinated, and  if 
so,  character 
of  cicatrix. 

Not  vaccinated 

Month  of 
progn'cy 

wlicii 
attacked. 

8^ 

Stage  of  disease 
at,  vvliii'li  ii,l)or- 
tioii  occurred. 

Result. 
Recov- 

RernarkB. 

101 

Aborted  1st  day 

of  eruption. 
Aborted  Utii  day 
of  eruption. 

ered. 

102 

23 

" 

1  poor  scar. 

8 

« 

Child  at  birth  healthv  ; 
successfully  vaccinat'd; 

12   days    later   a    half- 

dozen  small jK^x  paiiules 

api>eared;    child    died 

of  erysipelas. 

103 

21 

Varioloid. 

1  fair     " 

8 

Delivered  Ist  day 
of  eruption. 

" 

Smallpox  eruption  ay)- 
peared  on  child  10  days 

104 

24 

" 

1  good   ' ' 

4 

Discharged 
carrying  fuetus. 

" 

after  birth  ;  infection 
in  ulero. 

105 

23 

" 

2  good  scars. 

8 

Discharged 
carrying  fa;tus. 

Delivered  at  term. 

106 

42 

Variola. 

1  fair  scar. 

2K 

Discharged 
carrying  fcctus. 

1 

107 

26 

Varioloid. 

2  poor  scars. 

9 

Delivered  at  term 

" 

108 

29 

" 

1  fair  scar. 

4 

Aborted  37th  day 
of  eruption. 

Foetus  showed  a  sparse 
vesicular  eruption. 

109 

25 

" 

2  good  scars. 

6 

Discharged 
carrying  fcetus. 

110 

35 

" 

2  fair     " 

6 

Aborted  28th  day 
of  eruption. 

111 

32 

" 

2  good  " 

6 

Aborted  1st  day 
of  eruption. 

112 

22 

Variola 
(hemor- 

Not vaccinated 

6 

Aborted  5th  day 
of  eruption. 

Died 
5th  day. 

113 

27 

rhagic). 
Varioloid 

Vaccinated 

2 

Discharged 

Recov- 

(mild). 

16  days  before 
eruption. 

carrying  foetus. 

ered. 

Smallpox  in  the  Foetus.— During  an  attack  of  smallpox  the  causative 
germ,  in  all  probability,  circulates  in  the  blood  stream  of  the  patient. 
Therefore,  when  a  pregnant  woman  suffers  from  variola,  we  would 
naturally  expect  the  foetus  to  be  likewise  attacked  and  to  pass  througli 
all  of  the  phases  of  the  disease  simultaneously  with  the  mother.  Strange 
to  say,  however,  this  is  but  seldom  the  case.  In  a  minority  of  instances 
the  foetus  does  become  infected,  but  not  synchronously  with  the  infection 
of  the  mother.  Indeed,  in  most  cases  in  which  the  fatus  develops 
smallpox  it  passes  through  a  period  of  incubation  in  the  same  manner 
as  if  it  were  in  the  outer  world ;  that  is  to  say,  about  two  weeks  elapse 
from  the  time  the  mother  shows  symptoms  until  the  disease  appears  in 
the  child.  From  this  observation,  which  is  quite  generally  the  experience 
of  most  writers,  it  would  seem  that  the  infant  in  utero  ordinarily  becomes 
infected,  not  through  the  maternal  circulation,  but  through  contact  or 
proximity.  If  the  blood  of  the  mother  were  the  infecting  medium  the 
disease  in  the  foetus  should  be  of  constant  occurrence.  There  are  rare 
cases  in  which  the  foetus  contracts  smallpox  after  an  exposure  to  the 
disease  by  a  mother  who  happens  to  be  an  immune.  In  such  cases  it 
is  difficult  to  understand  how  the  causative  agent  could  reach  the 
infant  in  utero  save  through  the  maternal  blood. 

Smallpox  may  be  communicated  to  the  foetus  in  utero  at  any  time 
between  the  fourth  month  of  gestation  or  possibly  earlier  and  the  full 
term.  When  infection  takes  place  in  the  earlier  stages  of  intrauterine 
life,  the  foetus  usually  perishes  and  is  expelled  in  three  or  four  days, 
or  it  may  be  retained  for  three  or  four  weeks  after  hfe  has  become 


222 


SMALLPOX 


extinct.  There  are  well-authenticated  instances  in  which  the  child 
suffers  and  recovers  from  an  intrauterine  attack  of  smallpox,  and  is 
born  at  term  with  variolous  scars. 

When  the  infection  takes  place  during  the  later  periods  of  pregnancy 
the  child  at  birth  may  be  covered  with  the  eruption,  which  may  represent 
any  stage  of  development.  This  occurrence  is  so  well  authenticated 
that  it  is  unnecessary  to  quote  any  cases  from  literature.  We  have 
ourselves  met  with  four  or  five  instances  of  this  character.  In  one 
case  a  six  months'  foetus  presented  a  few  red  spots  which  evidently 
resulted  from  a  mild  vesicular  eruption.  In  another  instance  an  infant 
was   born  at  the  eighth  month,  on  whose  body  at  birth  the  eruption 


Fig. 43 


Smallpox  contracted  in  utero  and  appearing  nine  days  after  birth  ;  the  vaccine  lesion  seen  upon 
the  arm  resulted  from  vaccination  on  the  second  day  after  birth. 


was  just  appearing.  In  a  third  case  a  four  months'  foetus  was 
expelled  on  the  thirty-seventh  day  of  the  maternal  eruption.  The 
eruption  on  the  child  was  rather  sparse,  consisting  of  two  whitish, 
variolous  pocks  on  the  sole  of  the  right  foot,  one  on  the  heel  of  the  left 
foot,  one  on  the  chest,  one  on  the  back,  and  two  firm  lesions  upon  the 
palm  of  each  hand. 

The  fourth  case  occurred  in  a  colored  child  (Fig.  44)  born  at  eight 
months,  on  the  thirty-third  day  of  the  mother's  eruption,  the  latter 
suffering  only  from  a  very  mild  varioloid.  The  infant  had  evidently 
been  dead  for  some  days,  as  the  epidermis  was  detached  from  the  under- 
lying corium  in  large  areas.  Smallpox  lesions  in  the  pustular  stage 
(about  fifth  or  sixth  day)  were  present  upon  the  face,  extremities,  and 
body,  but  not  profusely.     It  was  calculated  that  the  exanthem  in  the 


Tim  vAfin<rrji<:s  of  sma/jj'ox 


223 


child    Ix'j^'jMi   ii-hoiit  twciiiy-seveii   (hiys  after  the  fniphoii   appcan-fl    in 
the  mother. 

The  child  of  a  variolous  mother  m;iy  he  iiifectcfl  with  srnallpfix 
in  utero  and  be  l)()rn  free  of  lesions,  the  (iniptioii  jipjxiarin^  some  days 
after  birth.  If  the  infant  is  infected  duririf^  parturition  the  outbreak 
of  the  eruption  may  be  delayed  for  a  fortnif^ht  after  it  has  entered  the 


Via.  44 


Colored  child,  born  dead  at  term,  with  the  smallpox  eruption  present  in  the  stage  of  pustulation, 
the  mother  at  the  time  convalescing  from  the  disease. 


world.  If  it  is  infected  earlier  the  eruption  may  appear  on  the  first, 
second,  or  third  day  of  life,  or  at  any  period  within  two  weeks.  We 
have  observed  this  phenomenon  on  numerous  occasions.  Fig.  43 
represents  a  child  born  on  the  first  day  of  the  mother's  eruption,  which 
was  hemorrhagic  and  rapidly  fatal.  The  infant  developed  the  eruption 
on  the  ninth  day  of  its  life  and  succumbed  to  the  disease  on  the  four- 
teenth day.  It  was  vaccinated  on  the  second  day,  on  admission  to  the 
hospital,  and  although  the  vaccination  took  it  was  not  sufficiently 
advanced  to  materially  modify  the  smallpox  exanthem. 


224  SMALLPOX 

The  frequency  of  fetal  infection  does  not  seem  to  bear  a  relationship 
to  the  severity  of  the  disease  in  the  mother.  Pregnant  women  suffering 
from  the  severest  form  of  confluent  variola  do  not  communicate  the 
disease  to  the  foetus  more  often  than  those  who  have  the  disease  in  the 
mildest  possible  form.  Indeed,  as  already  suggested,  infection  of  the 
foetus  may  take  place  through  the  mother,  although  she  personally 
remains  free  of  the  disease.  A  number  of  curious  cases  of  this  nature 
have  been  reported.  Jenner^  records  two  cases  which  came  under  his 
observation;  one  of  the  cases  is  detailed  by  him  as  follows: 

"A  few  days  previous  to  her  confinement  (Mrs.  W.)  she  met  with  a 
very  disgusting  object,  whose  face  was  covered  with  smallpox.  The 
smell  and  appearance  of  the  poor  creature  affected  her  much  at  the 
time,  and  though  she  mentioned  the  circumstance  on  her  return  home 
she  had  no  idea  that  her  infant  could  suffer  from  it,  having  had  smallpox 
herself  when  she  was  a  child.  During  a  few  days  after  its  birth  the 
little  one  seemed  quite  well,  but  on  th^  fifth  day  it  became  indisposed 
and  on  the  seventh  day  the  smallpox  appeared.  Mrs.  W.  was  not 
sensible  to  any  indisposition  herself  from  this  exposure,  nor  had  she 
any  appearance  of  the  smallpox."  Other  cases  of  the  same  character 
might  readily  be  quoted  from  literature. 

When  a  pregnant  woman  undergoes  smallpox  without  miscarriage 
occurring,  the  susceptibility  to  the  disease  is  not  destroyed  in  the  infant, 
except  in  rare  cases.  Susceptibility  to  the  vaccine  disease,  in  the  vast 
majority  of  instances,  is,  we  think,  evidence  of  susceptibility  to  smallpox. 
Now  and  then  an  infant  is  born  under  the  circumstances  named  that 
will  not  respond  to  vaccinia.  We  have  met  with  three  or  four  such 
cases.  A  woman  suffering  from  a  well-marked  varioloid  gave  birth 
in  the  hospital  to  a  child  at  term,  on  the  twenty yfirst  day  after  the 
appearance  of  the  maternal  eruption.  The  child  was  vaccinated  with 
glycerinated  lymph  on  three  successive  occasions,  but  without  success. 
It  remained  in  the  hospital  for  three  weeks  and  continued  perfectly 
well.  In  another  instance  a  woman  suffering  from  mild  varioloid  gave 
birth  to  a  child  at  term  during  the  initial  stage  of  the  disease.  The 
infant  was  vaccinated  on  successive  occasions  after  admission  to  the 
hospital,  but  without  securing  a  "take."  A  profuse  smallpox  eruption 
appeared  upon  the  child  on  the  seventeenth  day  of  its  life,  which 
proved  fatal. 

Concerning  the  occasional  failure  of  the  offspring  of  variolous  mothers 
to  respond  to  vaccination,  it  may  be  said  that  it  is  sometimes  very  difficult, 
under  ordinary  conditions,  to  successfully  vaccinate  very  young  infants. 
In  such  cases  a  successful  result  may  sometimes  be  obtained  at  a  later 
period — say,  at  the  age  of  four  or  five  months.  This  was  exemplified 
in  a  case  reported  by  Rigden,  in  which  a  mother  with  varioloid  gave 
birth  to  an  infant  at  term  during  the  height  of  her  eruption.  She  made 
a  good  recovery  and  was  able  to  nurse  her  child  almost  from  the  day 
of  its  birth.     The  infant  was  vaccinated  the  day  after  its  birth,  but 

1  Medico-Chirurgical  Transactions,  vol.  i.  p.  274. 


TiTE  vauii-:tii':h  <n<'  sma/jj'ox  225 

without  success.  Between  the  ;i<^'('  of  four  ;iimI  fi\c  monllis  jiiioIIkt 
atteniy)t  wjis  uuuh^  with  a  siicccssriil  rcsiill.. 

It  is  of  iiitci'cst  to  i)ot(^  tliat  in  tfic  case;  jiisl  (|iio(c(l  jind  in  our  (irsf 
case  the  child  in  each  instance  was  insusceptible  at  hirtli  tc)  l)otli  \;i(riiii;i 
and  sinallj)()x.  '^J'hc  failure  to  secure  a  successful  vaccination  in  our 
second  case  may  ])()ssil)ly  he  attri})uted  to  the  use  of  inert  virus. 

But  in  the  vast  nni  jority  of  insliinccs  sinidlj)ox  in  I  lie  prcj^nant  woman 
(k)es  not  destr-oy  the  susceptibility  to  vaccinia  in  I  lie  infant.  Our  own 
experience  and  that  of  other  writers  constitute  ade(|uat<'  proof  of  this 
statement.  Rigden^  reports  six  cases  of  successful  vaccination  in  infants 
born  of  mothers  suffering  from  small))ox.  In  these  ca.ses  vaccination 
was  performed  between  the  ages  of  three  and  six  months,  and  was 
uniformly  successful.  We  have  in  a  score  or  more  of  instances  success- 
fully vaccinated  children  wlio  were  born  of  variolous  mothers;  some  of 
these  infants  were  vaccinated  as  soon  as  they  were  born,  while  others 
were  only  successfully  vaccinated  several  mont/:s  later.  A  picture  of  a 
successful  result  of  a  vaccination  at  birth  is  shown  in  photograph. 
(Fig.  ]  in  the  chapter  on  Vaccinia.) 

When  the  infection  has  occurred  in  utero,  vaccination  of  the  infant  at 
birth  frequently  mitigates  the  character  of  the  subsequent  eruption. 
If  a  week  or  more  elapses  between  the  time  of  vaccination  anrl  the 
development  of  the  variolous  exanthem,  the  lesions  are  apt  to  be  modified. 
When  the  eruption  develops  within  the  first  week  after  birth,  little  or 
no  modification  is  to  be  expected. 

We  must  dissent  from  the  view  expressed  by  Roger^  that  smallpox 
in  the  newborn  infant  differs  clinically  in  any  essential  manner  from 
variola  in  the  adult.  Roger  contends  that  infants  born  of  variolous 
mothers  usually  present  a  more  or  less  latent  smallpox,  characterized 
by  hypothermia,  with  or  without  a  slight  eruption  which  commonly 
comes  out  in  crops  and  aborts  in  the  papular  stage.  There  is  also  a 
tendency  to  icterus;  a  fatal  termination  occurs  in  most  cases.  Roger 
says:  "At  first  sight  the  newborn  appeared  well  constituted;  their 
general  condition  was  good,  and  nothing  could  have  caused  a  congenital 
infection  to  be  suspected  if  one  had  not  taken  their  temperature.     All 

of   the   infants   were   hypothermic In   six   infants   death 

occurred  without  their  presenting  any  symptoms  suggesting  variola  in 
any  way."  We  have  on  a  ninnber  of  occasions  seen  newborn  infants 
develop  severe  and  even  confluent  smallpox.  We  are  not  familiar  with 
a  congenital  variola  which  may  exist  without  an  eruption  or  be  char- 
acterized by  a  sparse  exanthem  which  is  arrested  in  the  papular  stage. 
That  most  infants  born  of  variolous  mothers  are  not  really  suffering 
from  smallpox  at  birth  is  proved  by  the  fact  that  they  will,  in  the  vast 
majority  of  cases,  respond  to  vaccination. 

1  British  Medical  Journal,  February  24.  1S77. 

2  Les  Maladies  Infectieuses,  Paris,  1902. 


15 


226  SMALLPOX 


THE  URINE  IN  SMALLPOX. 

That  excellent  French  physician  and  teacher,  Trousseau,  early 
observed  that  albumin  was  frequently  found  in  the  urine  in  smallpox. 
He  says :  "Albuminuria  is  almost  as  common  in  confluent  smallpox  as 
in  scarlet  fever.  There  is  this  difference,  however,  that  in  scarlatina 
the  albuminuria  appears  during  the  decline  of  the  disease,  and  in 
confluent  smallpox  during  the  acute  period  of  the  disease.  Extensive 
observations  by  Abeille  have  shown  that  in  confluent  smallpox,  as  in 
scarlatina,  albuminuria  is  met  with  in  about  one-third  of  the  cases." 

Our  own  observations  are  based  upon  1088  urinary  examinations  in 
128  cases  of  smallpox.  The  specific  gravity  was  determined  in  the 
ordinary  manner  with  the  urinometer;  524  examinations  gave  an 
average  specific  gravity  of  1018.  The  presence  of  indican  and  the 
amount  thereof  both  exhibited  marked  variability.  Some  cases  of 
severe  variola  showed  a  considerable  amount  of  indican,  while  in  others 
it  was  absent.  The  diurnal  fluctuations  in  amount  were  striking;  it 
was  not  uncommon  to  find  an  abundance  one  day,  and  twenty-four 
hours  later  to  note  its  absence. 

In  selecting  the  subjects  whose  urine  was  to  be  examined,  patients 
with  very  mild  varioloid  who  were  scarcely  ill  were  excluded.  The 
urine  was  repeatedly  examined  in  83  patients  suffering  from  variola 
and  in  26  patients  with  varioloid.  Of  83  cases  of  variola,  66|  per  cent, 
showed  albumin  some  time  during  the  course  of  the  disease.  Of  28 
cases  of  varioloid,  60  per  cent,  showed  albumin  during  the  course  of 
the  disease. 

That  the  presence  of  albumin  did  not  indicate  merely  a  febrile 
albuminuria  is  evidenced  by  the  fact  that  casts  were  found  in  a  con- 
siderable proportion  of  cases.  Surprising  to  relate,  the  percentage  of 
cases  of  varioloid  in  which  casts  were  found  is  somewhat  greater  than 
of  variola;  43  per  cent,  of  the  83  cases  of  variola  showed  casts  in  the 
urine,  while  of  the  28  cases  of  varioloid  50  per  cent,  showed  casts.  The 
comparative  frequency  of  albumin  and  casts  in  fatal  cases  as  contrasted 
with  those  that  recovered  may  be  seen  from  the  following  figures.  Of 
38  cases  of  fatal  smallpox,  30,  or  84.47  per  cent.,  showed  albuminuria, 
and  19,  or  50  per  cent.,  showed  casts.  Of  90  cases  that  recovered,  45. 
or  50  per  cent.,  had  albumin  in  the  urine,  and  41,  or  45.55  per  cent., 
showed  casts. 

It  is  of  interest  to  note  the  period  at  which  albumin  and  casts  first 
appeared  in  the  urine  in  these  cases : 

Albumin  in  Fatal  Cases.  Casts  in  Fatal  Cases. 

Cases. 

5th  day  or  before 

6th  to  10th  day  . 
11th  to  15th  day  . 
16th  to  20th  day  . 
After    20th  day  . 


.  16  or  52  per  ct.  5th  day  or  before    .    .    .    9  or  47  per  ct. 

7  "  37 


9  "  29  "  6th  to  10th  day  . 

3  "    9.7  "  11th  to  15th  day  . 

0  "    0  "  16th  to  20th  day  . 

3  "    9.7  "  After    20th  day  . 


1  "  5.5 
1  "  5.5 
1  "    5.5 


77//';  UltlNI<:  IN  SMAIjIJ'OX  227 


Ai.BUMrN  TN  Oases 

THAT  KeOOVERJCI). 

(JasTS  in  CahICH  THAI'  PtKCOVKKKI). 

Cases. 

OlHfH, 

tAh  flay  or  before 

.    .    .  24  or  53.5  per  ct. 

5th  flay  or  before    .     .    .  11  or  2';.«  per  ct. 

(Hh  to  ]Oth  (lay  . 

.    .    .  12  "  2fi.G     " 

Otli  to  10th  flay  .    .    .    .  10  "  :',;<       " 

nth  toir.thdny  . 

.     .     .     4  "     H.6     •' 

nth  to  15th  ^ay  ....    7  "  17.1     " 

Kith  to  20th  (hiy  . 

.     .     .     4 "     8  0     " 

Ifith  to  20th  (lay  .    .     .    .    5  "  12.2     " 

After    20th  (lay  . 

.     .     .     1  "     2.2     " 

After     20th  flay  ....    2  "    4,8     " 

It  will  1)0  seen  from  the  above  ta})le,s  tliat  wlien  al}»iirnin  i.s  foiiiul  in 
the  urine  it  usually  appears  early.  In  over  half  of  the  eases  in  wliieh 
it  was  present,  it  was  first  discovered  on  or  before  the  fifth  day  of  the 
eruption.  The  onset  of  albuminuria  seemed  to  be  about  the  same  in 
fatal  eases  as  in  cases  endinn;  in  recovery.  Tube  casts  when  present 
were  also  found  comparatively  early.  The  tables  would  indicate  that 
in  fatal  cases  they  were  present  at  an  early  period  in  a  larger  percentage 
of  cases  than  in  favorable  cases.  We  desire  to  point  out  the  fact  that 
albumin  and  casts,  singly  and  together,  may  first  appear  in  tlie  urine 
late  in  the  course  of  the  disease,  even  when  convalescence  is  established. 

Another  observation  of  interest  is  that  the  urine  from  day  to  day 
will  exhibit  striking  differences.  It  will  be  seen  from  the  appended 
report  of  eases  that  albumin  and  casts  were  not  present  daily  from  the 
time  of  first  appearance,  but  at  irregular  periods.  For  instance,  in 
some  eases  the  urine  would  contain  albumin  and  casts  for  several  con- 
secutive days,  then  perhaps  on  alternate  days,  and  then  the  urine  might 
be  free  of  these  for  a  week  or  thereabouts,  suffering  a  return  a  few  days 
later.  It  is  evident  that  a  single  examination  of  the  urine  under  such  con- 
ditions might  readily  fail  to  detect  the  presence  of  the  abnormal  urinary 
constituents.  The  persistence  of  albumin  and  casts  in  the  urine  was 
also  most  variable.  In  some  cases  they  would  be  present  only  for  a 
few  days  and  would  then  permanently  disappear.  In  other  cases  they 
would  persist  for  two  or  three  weeks  or  even  longer.  In  at  least  two 
cases,  both  suffering  from  smallpox  with  discrete  eruptions,  tube  casts 
were  present  in  the  urine  when  the  patients  were  discharged  from  the 
hospital.  Both  of  these  patients  were  young  men  and  had  not  had,  to 
their  knowledge,  any  antecedent  kidney  disease. 

It  was  not  uncommon  for  tube  casts  to  precede  the  presence  of  albumin 
in  the  urine  and  to  persist  after  its  disappearance.  Indeed,  in  seven 
cases  casts  were  found  in  the  urine  when  albumin  was  absent.  This, 
observation  demonstrates  the  inadequacy  of  the  albumin  test  in  deter- 
mining the  presence  of  disease  of  the  kidneys,  and  emphasizes  the 
importance  of  examining  the  urinary  sediment  under  the  microscope. 

The  occurrence  of  ur?emic  seizures  in  smallpox  is  extremelv  uncom- 
mon.    Convulsions,  except  during  the  initial  stage,  are  rarely  met  with. 

To  what  extent  the  condition  of  the  kidneys  may  contribute  to  the 
coma  that  is  not  infrequently  observed  in  bad  cases  of  confluent  smallpox 
is  a  question  difficult  of  solution.  CEdema  of  the  lower  extremities  is 
frequently  seen  during  convalescence,  but  this  may  be,  in  at  least  some 
measure,  attributed  to  other  causes.  It  may  in  general  be  stated  that 
the  clinical  manifestations  of  variolous  nephritis  are  much  less  con- 
spicuous than  those  characterizing  this  complication  in  scarlet  fever. 


228  SMALLPOX 

Arnaud^  made  1248  urinary  examinations  in  400  cases  of  smallpox. 
He  states  that  95.3  per  cent,  of  these  patients  had  albuminuria.  The 
cases  were  classified,  according  to  the  amount  of  albumin  present,  into 
abundant,; moderate,  slight,  and  minimal  albuminuria: 

a.  Abundant  albuminuria  (above  50  gms.  to  the  litre)       .       .       .      36  cases  or   Sperct. 

6.  Moderate  "  (20  to  50  gms.  to  the  litre)  ...      91        "        22.75  " 

c.  Slight  "  (0.05  to  20  gms  to  the  litre)        .        .        .145        "       36.25  " 

d.  Minimal  "  (0.005  to  0.05  gm.  to  the  litre)     .        .        .109        "        27.25  " 

e.  Absent 19       "         4.7     " 

400 

Arnaud  employed  delicate  reagents^  to  determine  the  presence  of  the 
minutest  quantities  of  albumin.  Other  investigators  have  obtained 
results  which  vary  greatly.  It  is  evident  that  the  figures  would  be 
markedly  influenced  by  the  number  of  examinations  made  and  the 
delicacy  of  the  tests. 


Lyons         

Bourru  (These  de  Paris,  1874) 
Couillaut  (ibid.,  1881-82) 
Bourgin  (Thfese  de  Lyon,  1885). 
Robin  (Bull,  de  I'Acad.  de  mt'd., 


XX.) 


found  albumin 

1  in    50  cases  or  2  pe 

15    "    79 

"      18.9 

42    "  114 

'      38.8 

77    "  214 

'      36 
50 

11    "    38 

'       28.95 

Roger  (Maladies  infectieuses,  Paris,  1902) 

Arnaud  remarks  upon  the  daily  variations  in  the  amount  and  in  the 
presence  of  albumin,  and  counsels  repeated  examinations.  He  further- 
more states  that  albuminuria  persisted  after  convalescence  in  75  per 
cent,  of  his  cases.  In  other  words,  three-quarters  of  the  patients  when 
convalescent  still  had  albumin  in  the  urine — to  be  sure,  in  minimal 
quantities  in  most  cases.  He  contends  that  variolous  albuminuria,  like 
most  albuminurias  accompanying  infectious  diseases,  is  not  simply 
functional,  but  is  related  to  a  structural  alteration  in  the  kidneys. 
In  proof  of  this  he  cites  the  results  of  histological  examination  of  the 
kidney  in  13  cases  of  smallpox. 

He  found,  even  in  cases  of  minimal  albuminuria,  marked  pathological 
changes  in  the  kidney  structure.  These  organs  examined  in  the  acute 
stages,  even  in  the  absence  of  clinical  manifestations  of  nephritis,  pre- 
sented a  constant  alteration.  The  changes  were  briefly  of  two  types: 
first,  an  interstitial  cell  infiltration,  and,  second,  lesions  of  the  epithelium 
of  the  tubules.  Albuminuria  is  slight  where  the  interstitial  changes  are 
found,  and  more  abundant  where  the  epithelium  is  involved.  Arnaud 
believes  that  in  light  cases  the  kidneys  may  entirely  recover,  but  in 
most  instances  a  renal  defect  is  left,  which,  though  compatible  with  a 
satisfactory  physiological  state,  may  under  certain  conditions  be  awa,kened 
or  brought  into  evidence.  Pregnancy,  muscular  fatigue,  alimentation, 
digestive  troubles,  etc.,  may  thus  excite  albuminurias  which  are  often 
spoken  of  as  physiological,  cyclical  or  intermittent,  but  which  represent  in 
reality  a  reawakening  of  a  process  which  had  its  origin  perhaps  in  some 
infectious  disease. 

1  Revue  de  m6decine,  1898,  tome  xviii.  p.  392. 
"  Millard's  test  and  the  sulphate  of  soda  test. 


CHAPTER    V. 

SMALLPOX   (Continued). 
COMPLICATIONS  AND  SEQUELS  OF  SMALLPOX. 

As  would  be  naturally  expected,  the  skin  is  most  commonly  the  seat 
of  complications  in  variola.  The  secondary  pyogenic  infection  of  the 
skin  gives  rise,  as  has  already  been  staterl,  to  imprfi(/o  lesions.  These 
are  so  common  that  they  have  been  described  under  the  head  of  symp- 
tomatology. The  postvariolous  toxic  and  septic  rashes  have  also  been 
alluded  to  under  this  caption. 

Boils  constitute  the  most  frequent  complicating  disorder  met  with  in 
smallpox.  But  few  patients  pass  through  an  attack  of  variola  vera 
without  suffering  from  numerous  furuncles.  The  subjects  of  confluent 
smallpox  suffer  more  severely  than  those  who  have  a  lighter  form  of 
the  disease.  Even  patients  with  varioloid,  however,  are  not  always 
exempted  from  this  troublesome  complication.  The  furuncles  develop 
most  commonly  after  the  stage  of  decrustation,  about  the  twentieth  or 
twenty-fifth  day  of  the  disease. 

Subcut;aneon3  Abscssses. — Subcutaneous  abscesses  are  commonly 
associated  with  the  more  superficial  furuncular  inflammations.  These 
may  occur  upon  any  part  of  the  body  surface,  but  involve  with  pre- 
dilection the  scalp,  face,  arms,  and  legs.  They  are  often  preceded  by 
a  cellulitis  or  a  phlegmonous  inflammation  of  the  skin  and  subcutaneous 
tissues.  The  patient  first  experiences  soreness  and  pain  in  the  affected 
portion  of  the  body.  The  skin  is  seen  to  be  swollen,  infiltrated,  and 
reddened.  In  the  course  of  several  days,  fluctuation  may  be  detected, 
and  on  incision  large  quantities  of  pus,  even  as  much  as  a  pint,  may  be 
evacuated.  The  entire  skin  of  the  leg,  arm,  or  scalp  may  be  extensively 
undermined  by  these  accumulations.  Besides  being  very  painful  these 
purulent  collections  are  accompanied  by  high  fever  of  a  septic  type. 
We  have  known  such  a  fever  to  continue  as  long  as  one  hundred  and 
twenty-six  days,  the  patient  ultimately  recovering.  Sometimes  an 
insignificant  and,  at  times,  undiscoverable  purulent  focus  will  send  the 
temperature  up  four  or  five  degrees,  whereas  in  other  patients  a  large 
abscess  may  be  present  without  much  febrile  disturbance. 

In  confluent  smallpox  subcutaneous  abscesses  may  destroy  life  through 
the  production  of  an  intense  septica?mia.  It  is  surprising,  however,  how 
patients,  worn  down  by  a  severe  and  exliausting  disease,  are  frequently 
able  to  successfully  combat  the  pus  absorption  until  convalescence  is 
fully  established.  \Ye  recall  a  young  man,  who,  after  a  severe  attack 
of  smallpox,  became  the  subject  of  a  most  protracted  series  of  abscesses. 


230 


SMALLPOX 


For  six  or  eight  weeks  purulent  collections,  varying  in  size  from  a 
hickory  nut  to  an  egg,  were  almost  daily  evacuated.  The  scalp  and 
integument  of  the  face  were  undermined,  the  pus  communicating  with 
the  surface  through  numerous  fistulous  openings.  No  part  of  the 
cutaneous  surface  remained  free;  in  all,  this  patient  suffered  from  no 
less  than  two  hundred  abscesses.  Although  greatly  emaciated  he  was 
subsequently  restored  to  health.  Fig.  45  shows  the  fseudokeloidal 
elevations,  made  up  of  hypertrophic  granulation  tissue,  which  were  left 
after  the  healing  of  the  abscesses  on  the  face. 


Fig.  45 

^Kmw 

^% 

■  1 

A 

.^ 

d 

if^HHI 

Fseudokeloidal  elevations  following  abscesses  upon  tbe  face. 


Carbuncles, — Carbuncles  may  develop  during  convalescence  from 
smallpox,  but  in  our  experience  they  occur  with  great  rarity.  We  recall 
a  carbuncle  which  began  upon  the  back  of  the  neck,  about  the  end  of 
the  third  week,  in  a  patient  who  suffered  from  a  well-pronounced  attack 
of  discrete  variola. 

Erysipelas. — This  complication,  when  it  develops,  usually  appears  at 
the  end  of  the  second  or  third  week  of  the  disease.  The  face  is  the 
region  most  often  affected,  although  the  process  may  attack  the  extrem- 
ities or  trunk.  At  times  a  diffuse  erysipelatoid  inflammation  of  the  skin 
occurs  without  the  actual  development  of  a  true  erysipelas.  Both  of 
these  conditions  are  attended  with  high  fever  which  rises  in  the  evening 
and  remits  in  the  morning.  During  the  epidemic  of  1901-02,  among 
approximately  two  thousand  cases  of  smallpox,  we  encountered  about 
ten  instances  of  erysipelas.    Considering  the  multiple  abrasions  of  the 


COMPLWATIONS  AND  Sf'^Qd/'JLA'J  OF  SMALLPOX  'I'M 

skin,  the  lowered  condition  of  the  patient's  vit;dity,and  tJie  ahiujst  ron- 
stant  presence  of  streptococci  on  the  cutaneous  surface,  it  is  surjjrising 
that  erysipelas  does  not  more  often  attack  the  smallpox  sufferer.  Almost 
all  of  our  patients  who  contracted  erysifjclas  recovered;  some,  however, 
unable  in  their  exhausted  condition  tf)  withstand  the  superadded  infec- 
tion, succumbed  to  the  disease. 

Bed-sores. — Bed-sores  occasionally  octmr  in  the  course  of  smallj)ox,  as 
they  do  in  other  protracted  diseases.  They  are  far  less  frequent  at  the 
present  time  than  in  earlier  days.  They  result  from  pressure,  mal- 
nutrition, and  uncleanliness,  and  may  usually  be  avoided  by  careful 
nursing. 

Gangrene. — At  times,  during  the  pustular  stage  of  smallpox,  the 
swelling  and  inflammation  of  the  skin  may  be  so  great  as  to  produce 
multiple  areas  of  necrosis.  Sloughing  of  the  skin  may  also  result  from 
undermining  of  the  integument  by  subcutaneous  abscesses. 

Apart  from  these  losses  of  cutaneous  tissue,  spontaneous  gangrene  of 
the  skin  occasionally  occurs  during  the  course  of  variola.  The  genitalia 
are  the  parts  most  commonly  involved,  (langrene  of  the  scrotum  is  a 
complication  of  great  gravity,  for  most  patients  thus  attacked  succumb 
to  the  disease.  It  usually  manifests  itself  first  as  an  oedematous  swelling 
of  the  scrotum,  which  is  rapidly  followed  by  gangrene.  In  extensive 
cases  a  considerable  part  of  the  integument  is  lost,  exposing  to  view 
the  testicles,  which  remain  unaffected.  When  this  unfortunate  accident 
develops,  it  begins  about  the  end  of  the  second  week  of  the  eruption ; 
it  is  most  likely  to  develop  in  bad  confluent  cases. 

Gangrene  of  the  skin  is  not  limited  to  the  regions  above  mentioned. 
It  may  attack  almost  any  portion  of  the  cutaneous  surface.  During  the 
years  1901  and  1902  we  observed  three  cases  of  gangrene  of  the  scrotum 
and  five  cases  in  which  gangrene  occurred  upon  various  portions  of  the 
thigh.  In  some  of  the  latter  cases  extensive  destruction  of  the  cutane- 
ous, subcutaneous,  and  muscular  tissues  occurred,  the  sphacelated  areas 
attaining  at  times  the  size  of  the  palm  of  the  hand.  In  four  of  the  five 
cases  recovery  took  place  after  a  tedious  convalescence.  It  may  be  of 
interest  to  note  that  most,  if  not  all,  of  these  patients  suffered  from  a 
more  or  less  extensive  impetigo  variolosa.  In  the  malignant  epidemic 
of  smallpox  in  1871-72  neither  impetigo,  gangrene,  nor  the  septic  rashes 
were  encountered  as  frequently  as  during  the  last  epidemic  (1901-04). 
This  leads  us  to  emphasize  the  statement  that  the  character  of  the 
disease  and  the  nature  and  frequency  of  the  associated  complications 
appear  to  vary  greatly  in  different  epidemics. 

The  Ocular  Complications  of  Variola.^ — Since  Jenner's  discovery 
the  destructive  effects  of  smallpox  on  the  ocular  tissues  have  been 
greatly  lessened. 

In  the  analysis  of  over  2000  cases  of  smallpox  at  the  jNIunicipal  Hos- 
pital, in  1901-02,  pustulation  of  the  lid  borders  was  a  common  affection; 

1  The  above  section  on  "  Ocular  Complications  of  Variola  "  has  been  kindly  prepared  for  us  by  Dr. 
Burton  K.  Chance,  Assistant  Surgeon  to  Wills  Eye  Hospital,  Philadelphia,  and  Ophthalmic  Surgeon 
to  the  Germantown  Hospital. 


232 


SMALLPOX 


conjunctivitis  was  frequently  found  with  it  and  was  also  found  inde- 
pendently. There  were  36  instances  of  corneal  ulcer,  17  of  which  were 
followed  by  perforation  with  destruction  of  one  eyeball,  and  15  cases 
were  cured  without  perforation.  Of  these  cases,  15  were  in  unvaccinated 
individuals;  in  6-  others,  vaccinated  at  periods  more  or  less  remote,  the 
lesions  were  less  severe;  10  cases  of  iritis  were  especially  noted. 

In  taking  up  the  systematic  consideration  of  the  action  of  variola  on 
the  various  parts  of  the  eye,  we  find  that  the  skin  of  the  lids  is  commonly 
a  site  of  the  pustular  eruption.     So  much  swelling  of  the  tissue  may 


Fig.  46 


Destructive  corneal  ulcer  with  panophthalmitis  occurring  in  the  latter  stage  of  severe  smallpox. 

accompany  the  eruption  that  the  eyes  cannot  be  opened  for  several 
days.  In  such  cases  severe  conjunciivitis  is  usual  and  often  leads  to 
corneal  ulceration.  The  edges  of  the  lids  are  liable  to  ulceration  and 
the  subsequent  cicatrization  distorts  them,  so  that  styes,  misplaced 
cilia,  eversion  of  the  lids,  or  occlusion  of  the  Meibomian  ducts,  etc.,  may 
result.  The  lids,  like  other  portions  of  the  skin,  after  the  subsidence  of 
the  eruption,  may  be  the  seat  of  abscesses  which  produce  various 
deformities  requiring  operation  later.  As  to  the  mucous  membrane  of 
the  lacrymal  passages,  pustules  may  also  form  there  and  give  rise  to 
acute  and,  later,  chronic  inflammation  of  the  canal  and  duct.  On  the 
orbital  borders  periostitis  with  caries  occurs  but  rarely. 


COMI'fJCATIONH  AND  .'■^I'JQf/l'Jf./h'  Oh'  SMALLI'OX  %\?, 

Passin^on  to  (.he conjunctiva,  w(;  find  iliiil,ii.s  in  olLcr  rchiil*!  diseases, 
it  is  conimoiily  afTect(*(l.  Inflaniniiilion  develops  aboiit  the  fiftii  day 
of  the  eruption;  the  con junctiva  jij)|)eiii's  (•on^!;ested  and  occasionally 
presents  a  catarrhal  infhuninidion  which  is  usnally  of  nioderatc  severity 
and  of  brief  duration,  yieldinj^  in  a  few  days  to  treatment.  An  exception 
to  this  appeared  in  a  young  man  under  our  care,  in  whom  severe  con- 
junctivitis bej^an  on  the  seventh  day,  and,  in  spite  of  careful  treatment, 
persisted  over  a  month. 

The  intensity  of  the  oj)hthalmia  is  related  directly  to  that  of  the 
pustular  eruption  in  general,  and  more  particularly  to  that  of  the  eruption 
on  the  face  and  eyelids.  On  the  conjunctiva  pustules  form  but  rarely; 
among  the  2000  patients  with  variola,  examined  by  us  in  1001  anrj  1902, 
they  were  noticed  in  only  two  or  thi'ee  instances.  When  tliey  do  occur, 
these  pustules  much  resemble  in  appearance  and  course  the  phlyctenular 
eruption  observed  in  strumous  children.  They  are  the  size  of  small 
lentils,  elevated  but  slightly,  and  usually  situated  midway  between  the 
corneal  margin  and  the  inner  and  outer  canthus.  They  appear  some- 
times at  the  limbus,  and  when  there  frequently  cause  ulceration  of  the 
cornea.  On  the  tarsal  conjunctiva  pustules  may  be  found  at  the  inner 
fold  and  on  the  caruncle,  but  never  at  the  fornix.  In  these  cases  the 
conjunctival  inflammation  markedly  resembles  that  of  gonorrhoea! 
infection;  the  inflammation  is  always  severe  and  is  accompanied  by 
profuse  secretion  and  chemosis. 

Subconjunctival  ecchymosis  may  occur  and  may  produce  intense 
chemosis  in  hemorrhagic  variola.  The  bacteriological  examination  of 
the  conjunctival  secretions  showed  the  presence  of  no  specific  or  hitherto 
undescribed  organisms,  but  there  were  present  in  abundance  staphylo- 
cocci, streptococci,  and  pneumococci. 

The  cornea,  according  to  other  observers,  is  not  subject  to  the 
specific  lesions  of  variola,  and  our  experience  would  lead  us  to  accept 
this  conclusion.  Among  over  9000  cases  of  smallpox  we  have  never 
seen  a  variolous  vesicle  or  pustule  on  the  cornea.  Ulceration  of  the 
cornea  does  occur,  but  it  is  usually  independent  of  the  general  process, 
being  rather  a  consequence  of  the  conjunctival  affection.  And  noAv, 
just  as  in  past  times,  it  is  the  most  fruitful  cause  of  blindness  as  a  sequel 
of  variola. 

During  a  period  of  over  thirty-five  years  but  two  persons  suftering 
from  smallpox  have  left  the  Municipal  Hospital  totally  blind.  Quite 
a  number  would,  however,  have  been  sightless  had  recovery  taken 
place. 

The  corneal  complications  may  arise  in  two  ways:  first,  either 
without  pustules  on  the  conjunctiva  or  by  pustulation,  especially  when 
this  is  at  the  limbus;  second,  at  about  the  fourteenth  or  fifteenth  day 
of  the  eruption,  during  the  stage  of  desiccation,  when  the  infection  is 
transmitted  from  some  broken-down  pustules,  as,  for  instance,  those 
of  the  skin  of  the  eyelids. 

The  corneal  inflammation  may  be  only  a  slight  superficial  haze 
confined  to  the  corneal  conjunctiva   or  Bowman's  membrane,   or  it 


234  SMALLPOX 

may  extend  rapidly  and  involve  the  entire  membrane.  Commonly 
near  the  margin  of  the  cornea  is  seen  a  small,  phlyctenular  bleb,  filled 
with  clear  fluid,  the  thin  and  delicate  covering  of  which  is  soon  macerated 
by  the  increased  conjunctival  discharge,  and  the  vesicle  is  ruptured, 
exposing  an  area  of  necrotic  tissue  of  grayish  color.  The  symptoms 
of  pain  and  redness,  although  usually  marked,  vary  in  intensity  and 
duration.  As  the  ulcerated  surface  spreads  the  several  layers  of  the 
cornea  are  involved  until  the  membrane  is  perforated,  and  the  aqueous 
humor  escapes  and  prolapse  of  the  iris  follows.  At  this  time  the  painful 
symptoms  abate.  In  bad  cases  pus  forms  in  the  anterior  chamber  or 
the  crystalline  lens,  and  the  vitreous  humor  may  be  extruded,  panophthal- 
mitis developing  from  a  general  suppuration  of  the  eyeball,  accompanied 
by  great  pain,  with  marked  bulging  of  the  lids.  Fortunately,  the 
majority  of  cases  present  a  milder  form  of  keratitis.  In  this  there  is 
only  a  circumscribed  superficial  inflammation,  which  heals  promptly 
and  leaves  the  eye  damaged  only  by  the  formation  of  an  opacity  as  the 
result  of  the  cicatrization  of  the  necrosed  area.  These  scars  cause 
marked  irregular  astigmatism,  which  greatly  interferes  with  the  acute- 
ness  of  sight. 

In  severe  cases  of  confluent  variola  rapid  destruction  of  the  cornea 
may  take  place  as  early  as  the  eighth  day.  It  is  usually  a  forerunner 
of  fatal  collapse.  In  some  instances  both  eyes  are  affected.  As  an 
example  of  this,  four  patients  in  our  own  wards  sank  rapidly  after  the 
destruction  of  both  eyes,  at  an  early  stage  of  the  general  disease.  In 
these  cases  it  was  noted  that  the  ulceration  was  preceded  by  a  grayish 
infiltration  of  the  bulbar  subconjunctival  tissues;  this  chemosis  rapidly 
increased,  rising  above  the  cornea  and  surrounding  it,  choking  off  its 
circulation.  Immediate  destruction  of  the  cornea  followed — a  true 
keratomalacia.  In  certain  instances  the  chemosis  is  so  great  as  to 
produce  an  oedema  of  the  subconjunctival  and  subcutaneous  tissues, 
even  to  such  an  extent  as  to  make  it  almost  impossible  for  the  lids  to 
be  opened. 

It  has  been  our  experience  to  find  the  ulceration  of  the  cornea  less 
extensive  in  size  and  degree  in  patients  who  have  once  been  vaccinated; 
consequently,  in  such  persons,  the  healing  is  more  prompt  and  the  sequelae 
are  less  damaging  to  the  integrity  of  the  eyeball. 

Parenchymatous  keratitis  after  variola  has  been  reported  by  but  few 
observers.  We  observed  two  cases.  The  first  was  in  a  young  man 
with  confluent  variola,  who  developed  about  the  seventeenth  day  a 
general  haziness  of  the  left  cornea.  This  gradually  improved,  leaving 
a  slight  opacity  behind  it.  About  two  weeks  later  an  ulcer  developed 
upon  this  site,  without,  however,  producing  serious  complications.  The 
second  was  in  a  young  woman,  aged  nineteen  years,  previously  of 
apparent  robust  health.  With  her,  marked  corneal  haze  was  noticed 
in  the  third  week  of  the  general  disease.  Her  convalescence  was  prompt, 
yet  on  discharge  from  the  hospital  there  was  noticed  well-defined  inter- 
stitial infiltration  and  iridocyclitis  associated  with  it.  For  two  months 
she  was  under  treatment  and  her  progress  toward  recovery  was  rapid. 


COMPLICATIONS  AND  .SI'XjUh'L/K  OF  SMAIJJ'OX  235 

The  uveal  tract  is  not  so  frequently  affected  as  tlic  covwt-.t.  In  our 
examinations  we  noted  ten  cases  of  irili.s,  not  plastic  in  form,  Wiit  f)f 
the  serous  type;  it  usually  marn'festcd  itself  from  ahf»ut  the  nintli  to 
the  nineteenth  day  of  the  eruption.  Otlu^r  observers  have  nrjted  iritis 
developing  after  the  subsidence  of  the  general  syuiptorns.  Slight  peri- 
corneal injection  was  noticed  sometimes  in  the  first  week,  accompanied 
by  lacrymation,  photophobia,  tenderness,  and  a  small  immobile  pupil. 
Although  this  ciliary  irritation  may  be  an  independent  aflcrtjori,  it  is 
usually  a  symptom  of  corneal  or  iritic  disease.  It  appears  to  be  more 
frequent  in  the  milder  cases,  and  may  persist  for  a  considerable  time 
after  the  termination  of  the  attack  of  variola. 

Choroiditis  was  revealed  only  by  the  presence  of  opacities  in  the 
anterior  or  posterior  part  of  the  vitreous.  We  had  the  opportunity  of 
studying  the  ocular  conditions  of  a  vigorous  young  man  for  several 
weeks  after  his  discharge  from  the  hospital;  in  each  eye  were  numerous 
floating  vitreous  opacities,  which  rapidly  lessened  as  he  regained  strength. 
In  none  of  the  cases  examined  did  we  find  circumscribed  choroidal 
inflammation,  nor  did  we  see  posterior  polar  cataract.  We  can  report 
no  cases  of  glaucoma  due  to  variola,  nor  any  cases  of  retinitis  or  neuro- 
retinitis.  But  all  these  have  been  reported  in  the  literature  of  variola 
by  other  observers. 

In  hemorrhagic  variola  there  is  no  reason  to  doubt  the  occurrence 
of  hemorrhages  into  the  retinal  sheet,  and  very  probably  hemorrhages 
into  the  optic  nerve  may  occur.  We  have  not  been  able  to  find  any 
such  cases  reported  as  actually  observed,  but  Knies  is  of  the  opinion 
that  such  hemorrhages  must  have  been  the  cause  of  some  of  the  affections 
described  as  neuritis  with  and  without  stasis  (choked  disk),  and  with 
and  without  termination  in  atrophy  of  the  optic  nerve. 

Meningitis  as  an  undoubted  sequel  is  rarely  found,  but  we  have 
come  in  contact  with  cases  of  meningitis  for  which  no  logical  cause 
could  be  found  except  a  remote  attack  of  variola. 

Ear  Complications. — The  pinna  of  the  ear  and  the  external  auditory 
canal  frequently  exhibit  numerous  lesions  of  smallpox.  During  the 
stage  of  pustulation  hearing  may  be  impaired  through  obstruction  of 
the  canal  by  swelling  caused  by  the  presence  of  the  eruption. 

Otitis  media  is  occasionally  produced  by  extension  of  inflammation 
from  the  throat  along  the  Eustachian  tube.  Upon  rupture  of  the 
tympanic  membrane  a  foul-smelling  pus  is  copiously  discharged.  One 
or  both  ears  may  be  involved.  While  this  complication  is  rather  unusual 
in  adults,  it  is  commonly  seen  in  children.  A  young  boy  under  our 
care,  suffering  from  a  severe  purulent  inflammation  of  the  middle  ear, 
developed  a  paralysis  of  the  facial  nerve  on  the  same  side.  This  was 
doubtless  due  to  extension  of  inflammation  to  the  nerve  as  it  traverses 
the  bony  roof  of  the  middle  ear. 

When  otitis  media  develops  it  usually  manifests  itself  during  the 
suppurative  or  desiccative  stage.  Often  before  attention  is  directed  to 
the  ear,  a  sharp  rise  of  temperature  occurs.  INIore  or  less  permanent 
impairment  of  hearing  may  result  from  this  suppurative  inflammation. 


236  SMALLPOX 

Writers  have  recorded  instances  in  which  extension  of  the  inflammation 
has  led  to  caries  of  the  petrous  portion  of  the  temporal  bone,  and  in 
other  cases  to  thrombosis  of  the  sinuses  of  the  brain. 

Respiratory  Organs. — Reference  has  already  been  made  to  the 
symptoms  produced  by  the  presence  of  the  eruption  in  the  larynx. 
When  the  lesions  in  the  neighborhood  of  the  vocal  cords  are  numerous, 
oedema  of  the  glottis  may  develop,  in  which  event  death  almost  invariably 
follows.  At  a  later  period  of  the  disease,  at  times  during  convalescence, 
ulceration  of  the  larynx  may  occur  with  the  production  of  a  perichondritis 
laryngex.    This  complication  is  fortunately  of  great  rarity. 

The  presence  of  variolous  lesions  in  the  trachea  and  bronchial  tubes 
leads  to  the  production,  respectively,  of  a  tracheitis  and  bronchitis, 
characterized  by  considerable  cough  and  expectoration  of  muco- 
purulent material.  These  symptoms  are  present  to  a  moderate  extent 
in  mo3t  well-pronounced  cases  of  smallpox. 

Lobar  Pneumonia. — We  have  found  lobar  'pneumonia  to  be  a  rather 
rare  complication  of  smallpox.  During  the  years  1901-02  we  observed 
but  one  frank  case  among  two  thousand  patients.  Catarrhal  pneu- 
monia has  likewise  been  infrequent  in  our  experience.  A  patient 
who  presented  for  some  days  a  patch  of  dulness  over  the  base  of  one 
lung  was,  at  a  late  stage  of  the  variolous  disease,  suddenly  seized  with 
severe  pain  in  the  chest  and  great  dyspnoea;  he  rapidly  sank,  and  died 
on  the  following  day.  Autopsy  disclosed  the  presence  in  the  lung  of 
a  large,  egg-sized  cavity  with  a  softened  and  ruptured  wall.  This 
probably  resulted  from  the  breaking  down  of  a  pulmonary  infarct. 
The  pleural  sac  contained  a  considerable  quantity  of  bloody  fluid. 

Pleurisy. — Of  the  internal  structures,  the  pleura,  perhaps,  is  most 
disposed  to  take  on  inflammatory  action.  When  pleurisy  occurs,  we 
usually  have  the  symptoms  well  marked;  yet  at  times  a  latent  form  of 
the  disease  may  exist,  of  which  the  patient  makes  no  complaint,  and 
which  may  be  wholly  overlooked  until  death,  when  a  post-mortem 
examination  will  reveal  a  pleural  cavity  filled  with  a  seropurulent 
material.  Acute  pleurisy  occurring  during  the  decline  of  the  eruption 
sometimes  proceeds  rapidly  to  empyema.  We  recall  a  patient  from 
whom  nine  pints  of  pus  were  removed  by  aspiration,  but  who  later 
succumbed  to  this  complication. 

Myocarditis. ^-It  is  but  natural  in  a  disease  of  the  nature  of  smallpox 
that  inflammatory  and  degenerative  changes  should  take  place  in  the 
heart  muscle.  The  myocardial  disease  may  result  from  the  pyrexia, 
the  variolous  poison,  or  the  associated  infections,  or  from  a  combination 
of  these.  Pericarditis  and  endocarditis  are  encountered  with  great 
rarity. 

Curschmann  remarks  having  seen  an  ulcerative  endocarditis  in  a 
case  of  confluent  smallpox.  We  observed  an  ulcerative  endocarditis 
on  autopsy  in  a  woman  who  was  sent  into  the  hospital  with  a  poorly 
developed  varioloid,  and  who  died  a  few  days  after  admission.  It 
was  evident  that  the  endocardial  disease  had  antedated  the  small- 
pox. 


COMPLICATIONS  AND  HI<:q(I I'lL/K  OF  SMALLPOX  %\1 

Phlebitis. — Phlebitis  uiid  venous  (liromhosis  iruiy  !>'■  mci  \\\\\\  as  a 
sefjiiel  of  variola,  especially  in  llic  lower  exireniities,  \i\\\\\\!i^  rise  to 
phlegmasia  alba  dolens. 

Joint  Disease — Joint  disease  occasionally  occurs  ;is  ;i  eornpliejition. 
or  sef(uel  ot"  siTia,llj)ox,  particuhirly  in  children.  One  or  iu(M-e  of  the 
joints  may  become  swollen  and  painful.  The  elbows  ap})ear  most 
likely  to  suffer.  Chondritis  and  osteitis  may  occur,  followed  by  suppu- 
rati(m  and  destruction  of  the  joint  and  fre(|uently  by  death.  Neve  has 
reported  a  number  of  cases  of  joint  and  bone  disease  following  smallpox 
in  children,  and  we  have  likewise  met  with  a  few  such  cases. 

Abdominal  Complications. — Smallpox  is  singularly  exempt  from 
abdominal  complications.  Diarrhcva  not  infrefpiently  occurs  as  the 
result  of  some  derangement  of  the  digestive  function.  While  this 
symptom  is  usually  controllable,  it  may  occasionally  be  so  severe  as  to 
precipitate  a  fatal  issue  in  those  greatly  weakened. 

Peritonitis  is  a  rare  complication,  and  when  it  occurs  may  be  attrib- 
uted to  some  local  cause. 

Orchitis. — We  encountered  this  complication  in  perhaps  six  or  eight 
patients  during  the  first  two  years  of  the  epidemic  of  1901-04.  The 
swelling  may  involve  the  entire  scrotum  or  may  be  limited  to  the  testicle 
and  epididymis.  One  or  both  organs  may  be  affected.  The  parts  often 
become  extremely  firm  to  the  touch.  The  enlargement  commonly  per- 
sists for  a  few  weeks  and  then  gradually  subsides,  although  a  variable 
amount  of  infiltration  may  continue  for  a  much  longer  time.  A  young 
man  recently  under  our  care  had  a  severe  confluent  smallpox,  complicated 
by  gangrenous  inflammation  of  the  arm,  iritis,  and  orchitis.  The  right 
testicle  was  swollen  to  three  times  the  size  of  the  left.  The  swelling 
was  firm  and  not  very  painful.  The  infiltration,  which  extended  along 
the  spermatic  cord  to  the  external  abdominal  ring,  reached  the  diameter 
of  an  adult  thumb.  It  is  said  that  the  analogue  of  this  condition, 
ovaritis,  may  develop  in  the  female.  We  have  never  observed  any 
symptoms  during  an  attack  of  smallpox  pointing  to  acute  disease  of  the 
ovaries. 

Phimosis. — Phimosis  not  infrequently  occurs  in  the  pustular  stage 
of  smallpox  as  a  result  of  the  swelling  of  the  areolar  tissue  of  the  prepuce 
occasioned  by  the  presence  of  the  eruption.  This  is  seen  most  commonly 
in  young  children. 

Nervous  System. — Psychic  disturbance  in  the  form  of  delirium  is  not 
uncommon  in  the  early  eruptive  period  of  smallpox.  Tt  may  in  some 
cases  supervene  at  a  later  period  of  the  variolous  process.  The  delirium 
may  persist  for  some  days  and  then  disappear,  or  in  rare  cases  it  may 
develop  into  a  confusional  insaniti/.  The  following  cases  of  insanity 
after  smallpox  have  come  under  our  observation: 

E.  M.,  aged  tw^enty-eight  years,  was  admitted  to  the  ^Municipal 
Hospital  on  November  29,  1903,  wdth  smallpox.  She  bore  one  good 
scar  from  a  vaccination  in  infancy  and  had  a  well-marked,  discrete 
variola.  On  December  6th  she  was  observed  to  be  tlelirious  at  times. 
The  mental  excitement   increased   and   the   patient   became  maniacal 


238  SMALLPOX 

and  had  to  be  strapped  in  bed.  From  this  time  on  there  were  occa- 
sional lucid  moments,  but  for  the  most  part  the  patient  was  delirious. 
She  would  sing  and  cry  and  appeared  to  be  completely  demented. 
Despite  the  fact  that  the  variolous  symptoms  had  quite  subsided,  the 
patient  continued  to  lose  weight  and  strength  and  died  in  an  insane 
condition,  apparently  from  exhaustion,  on  January  24,  1904,  two  months 
after  the  onset  of  the  attack  of  smallpox. 

Mrs.  A.  C.  was  admitted  to  the  Municipal  Hospital  on  March  10, 
1904,  with  a  modified  attack  of  smallpox.  She  bore  two  good  vaccination 
scars  from  infancy.  The  patient  had  never  exhibited  any  mental 
disturbance  before  the  attack  of  smallpox.  Family  history  negative. 
On  admission  the  patient  exhibited  evidences  of  mental  disturbance. 
She  spoke  at  times  rationally,  but  for  the  greater  part  talked  inco- 
herently and  almost  exclusively  upon  religious  topics.  I^ater  she 
became  maniacal,  jumped  from  the  bed  and  through  an  open  window; 
she  had  to  be  strapped  to  her  bed  to  prevent  violence.  At  times  refused 
to  eat  or  drink.  She  later,  when  released  from  her  bandages,  made 
several  more  attempts  to  jump  through  the  window.  She  was  removed 
to  her  home  on  April  9th,  her  mental  condition  having  remained 
unchanged. 

Another  patient,  L.  E.,  aged  thirty-seven  years,  who  had  recovered 
from  a  mild  attack  of  smallpox,  developed  religious  mania  after  con- 
valescence. He  was  transferred  to  a  hospital  for  the  insane.  It  was 
subsequently  ascertained  that  he  had,  before  his  attack  of  smallpox, 
suffered  from  a  similar  mental  disturbance. 

Several  cases  of  insanity  after  smallpox  are  reported  by  Seppilli  and 
Maragliano.  Of  three  instances  referred  to,  one  remained  permanently 
insane,  the  others  recovering  after  appropriate  treatment.  The  authors 
also  record  the  remarkable  case  of  a  violent  maniac,  who  had  been 
confined  for  about  six  weeks  in  an  asylum,  who  during  an  attack  of 
confluent  smallpox  was  restored  to  his  senses  and  after  convalescence 
from  variola  was  discharged  from  the  asylum  as  a  sane  man. 

Brain  symptoms  sometimes  appear  during  the  stage  of  decline.  We 
cannot  recall  a  single  instance  where  we  have  observed  clear  and  indub- 
itable evidence  of  acute  inflammation  of  this  organ,  yet  we  have  seen 
a  few  cases — perhaps  not  more  than  three — lapse  into  a  state  of  lethargy 
or  coma,  when  desquamation  had  almost  completed,  without  evincing 
any  preceding  symptoms  of  inflammatory  action.  We  have  met  with 
a  few  cases  in  which  there  were  peculiar  psychic  changes,  followed  by 
aphasia.  This  condition  we  attributed  to  the  presence  of  a  circum- 
scribed encephalitis.  Westphal  has  called  attention  to  cases  of  similar 
nature.  In  1872  he  presented  before  the  Berlin  Medical  Society  a 
patient,  who  during  smallpox  had  had  attacks  of  delirium  or  coma, 
followed  by  a  curious  disturbance,  characterized  by  slow,  measured, 
scanning  speech,  and  ataxia  of  the  upper  and  lower  extremities,  similar 
to  that  seen  in  tabes. 

Paralysis. — Various  paralyses  may  develop  during  the  course  of 
variola.     During  the  past  few  years  we  have  observed  eight  instances 


COMPTACATI()NHlANI>  SPJQUELjE  OF  SMALLPOX  289 

of  paralysis  among  about  3000  cases  of  smallpox.  Of  this  niirnher 
five  died  and  three  recovered. 

In  an  infant,  one  year  and  four  months  of  age,  we  observed  a  hemi- 
plegia occur  upon  the  first  day  of  the  (Tuy)tion.  This  succeeded  repeated 
convulsions  which  took  place  immediately  before  and  after  the  appear- 
ance of  the  exanthem.  It  is  probable  that  this  conchtion  was  not  inti- 
mately connected  with  the  variolous  process,  but  resulted  from  a  brain 
hemorrhage  excited  by  the  convulsive  paroxysms. 

In  another  patient,  a  woman,  paralytic  symptoms  appeared  during 
the  initial  stage  of  the  disease.  She  was  brought  into  the  hfjspifal  in 
a  stuporous  state,  barely  able  to  articulate.  There  was  great  difficulty 
in  swallowing  and  impaired  power  in  the  arms  and  legs;  the  loss  of 
power  in  these  members  subsequently  became  almost  complete,  but 
later  a  gradual  restoration  of  function  occurred.  The  patient  had  a 
most  pronounced  scanning  speech,  which  was  still  ])resent  when  she 
was  discharged  from  the  hospital.  The  reflexes  were  markedly  exag- 
gerated. 

The  third  patient,  a  young  colored  man,  had  a  severe  attack  of 
smallpox,  complicated  by  extensive  gangrene  of  the  scrotum  and  penis. 
At  the  end  of  about  ten  weeks  from  the  onset  of  the  disease  he  developed 
partial  loss  of  power  in  the  legs  and  arms.  He  could  walk  with  great 
difficulty  with  a  cane.  This  condition  persisted  to  the  day  of  his 
departure  from  the  hospital. 

Sometimes  the  spinal  cord  is  preponderantly  or  exclusively  affected, 
the  symptoms  being  those  of  a  paraplegia.  We  have  observed  a  half- 
dozen  or  more  instances  of  this  serious  complication,  of  which  the 
following  are  of  especial  interest: 

Case  L— C.  M.,  aged  thirty  years;  unvaccinated ;  was  seen  in  con- 
sultation on  April  22,  1902,  on  the  first  day  of  the  smallpox  exanthem. 
The  eruption  was  confluent  on  the  face  and  hands,  and  covered  thickly 
all  parts  of  the  body. 

The  pustides  began  to  shrink  on  the  eleventh  day;  the  secondare'  fever 
was  not  high,  and  there  was  no  delirium.  The  patient  was  progressing 
favorably  until  May  4th,  when  it  was  found  that  he  was  unable  to  void 
his  urine,  necessitating  catheterization.  On  the  following  day  paralysis 
of  the  lower  extremities  was  noted,  sensation  being,  however,  preserved. 
There  was  also  complete  loss  of  power  over  the  bowels  and  bladder. 
Immediately  preceding  the  paralysis,  there  were  hebetude  and  drowsi- 
ness, which  persisted  for  several  days.  A  week  later,  on  ^Nlay  12th, 
slight  motion  returned  in  the  legs.  A  gradual  improvement  in  all  of 
the  symptoms  then  set  in.  By  June  23d  the  patient  was  able  to  walk 
a  few  blocks  without  difficulty,  although  control  over  the  bladder  and 
rectum  was  not  quite  perfect.     Complete  lecovery  ultimately  resulted. 

Case  II. — INIrs.  N.,  married,  aged  nineteen  years,  was  admitted  to 
the  hospital  with  a  smallpox  of  considerable  severity.  She  was  progress- 
ino;  well  when  durina;  the  third  week  of  the  disease  she  became  unable 
to  move  her  legs.  Sensation  was  impaired,  but  not  entirely  lost.  She 
had  loss  of  control  of  the  bladder  and  rectum.     Within  a  few  davs 


240  SMALLPOX 

partial  motion  was  restored  in  the  lower  limbs.  Later  diarrhoea  set  in 
and  the  patient  died. 

Case  III. — J.  W.,  a  man  aged  thirty-eight  years,  was  admitted  to 
the  hospital  on  January  13,  1903.  He  had  a  scant,  modified  eruption, 
having  been  vaccinated  in  infancy.  About  a  dozen  lesions  were  present 
upon  the  anterior  surface  of  the  body,  a  few  were  scattered  sparsely 
over  the  extremities,  and  on  the  face  there  were  about  fifty  lesions. 
On  the  eighth  day  of  the  eruption  the  patient  developed  loss  of  power 
in  the  legs  so  that  he  was  unable  to  raise  them  from  the  bed.  Sensation 
was  impaired,  but  not  lost.  There  was  no  pain.  The  mental  condition 
was  good.  Later,  retention  of  urine  developed,  followed  after  some 
days  by  incontinence  of  urine  and  feces.  The  patient  died  on  the 
thirty-sixth  day  of  the  disease,  after  ten  days  of  high  and  irregular 
fever. 

Autopsy  disclosed  the  existence  of  a  number  of  abscesses  in  the 
kidneys.  A  culture  from  the  intradural  fluid  in  the  spinal  region 
revealed  the  presence  of  staphylococci. 

The  cord  from  this  patient  and  from  Case  II.  were  sent  for  study 
to  Prof.  W.  G.  Spiller,^  of  the  University  of  Pennsylvania.  The  spinal 
cord  from  Case  II.  had  been  hardened  in  alcohol  and  the  microscopic 
study  was,  therefore,  unsatisfactory,  although  nothing  distinctly  abnor- 
mal could  be  detected  in  the  cord.^ 

In  regard  to  Case  III.,  Prof.  Spiller  states:  "Strictly  speaking,  the 
case  was  one  of  diffuse  myelitis,  but  with  the  exception  of  a  part  of 
the  thoracic  cord  the  myelitis  was  almost  confined  to  the  anterior  horns 
and  was  an  anterior  polyomyelitis,  and  probably  of  vascular  origin." 

Grave  Lesions  of  the  Nervous  System  Complicating  Smallpox  with  but 
Scant  Eruption. — It  would  appear  that  in  rare  cases  the  poison  of  small- 
pox is  largely  expended  upon  the  nervous  system,  the  skin  escaping 
with  very  few  lesions.  These  cases  are  an  exception  to  the  general 
statement  that  the  gravity  of  smallpox  is  proportionate  to  the  extent 
of  the  eruption.  A  remarkable  case  of  this  character  came  under  our 
own  observation  during  the  year  1902. 

E.  M.,  a  burly  negro,  aged  twenty-seven  years,  was  admitted  to  the 
hospital  on  April  7,  1902.  The  patient  had  never  been  vaccinated. 
According  to  the  history,  the  initial  symptoms  had  been  well  marked — 
headache,  vomiting,  fever,  and  backache  having  been  present.  The 
entire  eruption  consisted  of  about  a  dozen  small  papules,  scattered 
over  the  face,  forearms,  hands,  and  trunk.  These  were  arrested  in 
their  development  and  dried  up  in  a  few  days,  as  occurs  commonly  in 
cases  of  varioloid.  The  patient  fell  into  a  state  of  hebetude  after  admis- 
sion, although  he  had  walked  to  the  ambulance.     He  became  progres- 

1  Prof.  Spiller  reported  the  full  findings  in  these  cases  in  a  paper  entitled  "  A  Report  of  Two  Cases 
of  Paraplegia  Occurring  in  Variola,  One  heing  a  Case  of  Anterior  Poliomyelitis  m  an  Adult."  Other 
cases  in  the  literature  of  the  subject  are  referred  to.    Brain,  Autuinn,  1903,  London. 

2  Since  the  above  chapter  was  written  an  article  on ' '  Nervous  Complications  and  Sequelse  of  Small- 
pox," by  Dr.  Charles  J.  Aldrich,  has  appeared  in  The  American  Journal  of  the  Medical  Sciences, 
February,  1904.  The  author  reports  three  interesting  cases  of  aphasia  after  smallpox,  and  carefully 
reviews  the  entire  subject,  giving  a  full  and  extensive  bibliography. 


COMPIJCATIONS  AND  SMQf/h'f.A':  OF  SMALLI'OX  241 

sively  more  sfiiporoiis,  had  difriciilty  ii)  swallowiiij^,  and  pailial  ana-s- 
thesia  and  loss  of  power  in  the  legs.  Later,  complete  paraj)lcf,n"a  wifli 
incontinence  of  nrine  and  feces  developed.  He  died  on  the  fourteenth 
day  of  the  eru|>lion.  The  temperature  on  admission  (third  day  of 
eruption)  was  00.2°  V.;  it  later  fluctuated  for  nine  days  hcfwccn  this 
point  and  101°  ¥.,  rising  to  104°  F.  just  before  death. 

The  diagnosis  of  smallpox,  owing  to  the  poorly  developed  lesions,  was 
not  entirely  certain  until  about  ten  days  later,  when  the  wife  and  child 
of  the  patient  were  brought  into  the  hospital  with  variola.  Autopsy 
showed  great  softening  of  the  spinal  cord  in  the  region  of  the  lower 
dorsal  and  upper  lumbar  vertebne.  When  the  dura  over  this  area  was 
punctured  the  softened  cord  ran  out  like  pus.  From  this  portion  of 
the  cord  a  micrococcus  w^as  grown  on  culture.  The  brain  showed  no 
gross  changes  save  an  intense  congestion  of  the  pia  mater. 

It  is  interesting  to  note  that  in  one  of  the  cases  of  paraplegia  reported 
by  Westphal  the  patient  had  an  extremely  scant  eruption  and  the 
"disease  was  so  mild  that  the  patient  did  not  go  to  bed."  MacCombie 
has  also  called  attention  to  serious  disease  of  the  nervous  system  develop- 
ing in  the  course  of  mild  cases  of  smallpox. 

Peripheral  Neuritis. — Peripheral  neuritis  is  encountered  as  a  complica- 
tion or  sequel  of  smallpox  with  great  rarity.  In  the  case  of  paraplegia, 
to  which  we  have  already  referred,  in  which  no  microscopic  changes 
were  foimd  in  the  cord,  the  lesion  may  have  been  a  peripheral  neuritis. 
Combemale  believes  the  disorders  of  speech  occasionally  complicating 
smallpox  to  be  due  to  paralysis  resulting  from  the  action  of  toxins 
upon  the  peripheral  nerves. 

Disseminated  Spinal  Sclerosis. — An  interesting  case  of  typical  infectious 
disseminated  sclerosis  is  reported  by  Sottas.  A  young  man,  aged  eighteen 
years,  with  a  discrete  smallpox  eruption,  presented  during  his  illness 
most  severe  nervous  symptoms.  The  patient  was  semicomatose,  had 
a  slow  dragging  speech,  nystagmus,  general  paralysis,  atrophy  of  the 
muscles  of  the  trunk  and  limbs,  and  later  contractures.  At  a  subsequent 
date  there  were  characteristic  tremors,  exaggerated  reflexes,  inco- 
ordination  of  voluntary  movements,  and  great  mental  excitability. 

Septicaemia  and  Pyaemia. — Septicaemia  is  commonly  observed  in  the 
stage  of  decrustation  in  confluent  smallpox.  In  severe  cases  there  may 
occasionally  be  seen  during  the  third  week  a  high  and  irregular  fever, 
rapid  pulse,  low  delirium,  and  great  prostration,  without  there  being 
discoverable  any  pus  collection  to  account  for  these  s}Taptoms.  Pyaemia 
is  more  rare  than  would  be  supposed  from  the  writings  of  the  older 
physicians.  Abscesses  in  the  liver,  kidney,  and  lungs  have  been 
revealed  by  autopsies,  but  with  great  infrequency. 


16 


242  "       SMALLPOX 

THE  PATHOLOGY  OF  SMALLPOX. 

The  Histopathology  of  the  Pock. — The  microscopic  structure  of 
variolous  lesions  has  been  studied  by  Barensprung/  Auspitz  and  Basch/ 
Ebstein/  Rindileisch/  Unna/  Weigert/  Touton/  Renaut,^  Leloir,^ 
Buri/"  and  others. 

Weigert  regarded  the  primary  changes  in  the  epidermis  as  necrobiotic 
and  diphtheroid,  due  to  the  local  effect  of  the  smallpox  poison.  He 
claims  to  have  found  analogous  alterations  in  the  liver,  spleen,  kidneys, 
and  lymph  glands,  which  he  believes  to  be  specifically  variolous. 

Nearly  all  of  the  other  writers  mentioned  describe  the  early  changes 
in  the  skin  as  inflammatory  in  character. 

According  to  Barensprung,  cited  by  Curschmann,  the  red  spot,  which 
represents  the  first  clinical  evidence  of  the  pock,  is  produced  by  a 
circumscribed  hypera3mia  of  the  papillary  and  deeper  bloodvessels. 
The  papule  is  formed  by  peculiar  changes  in  the  cells  of  the  mucous 
layer  or  the  rete  Malpighii,  which  become  cedematous,  enlarged,  and 
granular.  The  vesicle  is  explained  by  an  exudation  of  clear  fluid  from 
the  papillary  bloodvessels,  separating  the  cells  above  referred  to.  It  is 
evident  from  later  studies  that  other  important  processes  (subsequently 
to  be  described)  enter  into  the  formation  of  the  vesicle. 

The  older  writers  believed  the  umbilication  to  be  due  to  a  hair  follicle, 
sweat  duct,  or  epithelial  strand  holding  down  the  centre  of  the  roof 
of  the  pock.  Auspitz  and  Basch  first  pointed  out  that  it  was  in  reality 
due  to  the  periphery  of  the  pock  swelling  more  rapidly  than  the  centre. 
This  view  is  corroborated  by  Unna,  of  Hamburg. 

Unna  has  carefully  studied  the  structural  changes  in  the  skin,  employ- 
ing the  most  modern  histological  technique."  The  following  description 
is  condensed  from  Unna's  detailed  account: 

The  development  of  the  variolous  vesicle  is  the  result  of  certain 
peculiar  degenerations  of  the  protoplasm  of  the  epithelial  cells.  The 
main  features  which  differentiate  the  vesicle  formation  in  smallpox 
from  that  in  chickenpox  are  the  slowness  of  growth  and  the  prompt 
addition  of  suppuration  to  the  epithelial  degeneration. 

The  changes  in  the  protoplasm  of  the  cells  of  the  mucous  layers  of  the 
epidermis  are  of  two  chief  varieties.  These  have  been  designated,  by 
Unna,  reticulating  and  ballooning  colliquation  (softening).  Both  are 
special  forms  of  fibrinoid  degeneration. 

Reticulating  colliquation  occurs  as  follows :  As  a  result  of  the  poison 
of  the  disease  the  protoplasm  of  the  cells  becomes  cedematous  and 

I  Die  Haut-Krankheiten,  1854.  2  virchow's  Archiv,  Bd.  xxviii.,  S.  337. 

^  Ibid.,  Bd,  xxxiv.,  S.  598.  *  Handbuch  der  pathol.  Gewebslehre,  1871. 

5  Virchow's  Arctiiv,  Bd.  Ixix.,  S.  409. 

6  Anat.  Beitriige  zur  Lehre  von  den  Pocken,  Breslau,  1874,  Helt  1. 

7  Vergleichende  Untersuch.  liber  die  Entwick.  von  Blaseu  in  der  Epidermis,  1882. 

8  Archives  de  la  dermat.  et  de  syph.,  1881. 

"^  Archives  de  la  physiol.  norm,  et  pathol.,  1880,  p.  307.  ' 

w  Monatshefte  f.  prakt.  Dermat.,  1892,  Bd.  xiv.,  1892. 

II  Histopathology  of  Diseases  of  the  Skin.  Translated  from  the  German  by  Dr.  Norman  Walker, 
1896. 


77//-;  I'M'IIOLOCV   <>/<'  SM.MJJ'OX  24'i 

midcr^'oes  jKirliiil  oi-  coiiiplcU;  li<|iicr;u:(,i«)ii,  Uiiis  (.unwvvUw^  IIk;  coll 
body  into  a  lar^e  cavity.  (Coagulation  of  the  albuminoid  bodies  set  free 
from  the  protoplasm  now  tnkes  place,  ksading  to  the  formation  of  a 
line  griundiir  prccipiliiic;  which  lies  on  the  well-jjreserved  nucleus  or 
the  tliiri,  disixMided  cell  wall.  The  nucleus  at  first  renuiiris  healthy,  but 
later  shows  fibrinoid  degeneration.  When  the  li(juci'action  of  the  cells 
is  partial,  protoplasmic  tral)ecu];c  form  which  coagulate  into  a  network, 
often  radially  arranged,  and  hold  the  nucleus  and  cell  mantle  together. 
The  name  "reticulating"  collicpiation  is  given  to  this  degeneration 
because  of  the  net-like  character  of  the  structure. 

Fig.  47 


Microphotograph  of  smallpox  pustule  showing  reticulating  epithelial  bands.    Magnified 

80  diameters. 

This  form  of  degeneration  corresponds  with  the  "alteration  cavitaire" 
described  by  Leloir  and  Renaut.  Leloir  maintained  that  the  cavity 
formation  invariably  began  with  a  dilatation  of  the  nuclear  cavity;  in 
other  words,  as  a  result  of  the  liquefaction  of  the  endoplasm. 

In  the  second  form  of  fibrinoid  metamorphosis — that  designated 
ballooning  colliquation — the  whole  protoplasm  of  the  cell  swells  up  and 
becomes  cloudy  and  opaque.  The  prickle  projections  are  withdrawn 
and  the  cell  becomes  rounded.  The  shape  of  the  cell  is  largely  deter- 
mined by  its  position  and  external  pressure,  and  may  be  round  or 
flat,  biscuit-shaped,  pointed,  or  drawn  out  into  septoe,  or  bands. 
Most  of  the  cells,  however,  have  the  form  of  hollow  spheres  or  balloons, 
the  predominance  of  which  gives  rise  to  the  name  "  ballooning  colli- 
quation." 


244  ^  SMALLPOX 

The  reticulating  degeneration  mainly  attacks  the  older  cells,  or  those 
in  the  upper  strata  of  the  Malpighian  layer,  and  the  ballooning  degen- 
eration the  younger  cells,  or  those  in  the  lower  strata.  This  is  accounted 
for  by  the  fact  that  the  younger  epithelia  contain  a  homogeneous  proto- 
plasm which  readily  undergoes  homogeneous  swelling  and  coagulation, 
whereas  in  the  older  cells  a  marginal  layer  separates  from  the  rest  of 
the  protoplasm  in  its  preparation  for  cornification. 

Formation  of  the  Smallpox  Vesicle.- — During  the  papular  stage  the 
cavity  formation  begins  in  the  upper  prickle-cell  layer  of  the  epidermis 
by  a  reticulating  colliquation  of  the  oedematous  epithelium.  Owing  to 
the  slow  advance  of  this  process  some  of  the  cells  are  compressed  and 
thus  part  of  the  cavity  is,  from  the  commencement,  divided  by  septa 
into  a  series  of  segments,  the  bands  running  perpendicularly  in  the 
centre  and  being  directed  outward  at  the  periphery. 

At  the  same  time  the  cells  of  the  lower  prickle  layer  undergo  ballooning 
colliquation.  The  cells  lose  their  prickles  and  become  detached  from 
one  another. 

As  the  pock  spreads  peripherally  the  differentiation  of  the  process 
in  the  upper  and  lower  strata  of  the  prickle  layer  becomes  more  marked. 
In  the  upper  part  the  cavity  extends  laterally,  many  of  the  marginal 
cells  liquefying  and  communicating  with  the  general  cavity.  In  the 
lower  part,  on  the  contrary,  ballooning  and  swelling  of  the  cells  develop 
slowly. 

At  the  height  of  the  development,  therefore,  the  pock  has  the  shape 
of  a  mushroom,  the  main  cavity  formation  taking  place  in  the  upper 
projecting  parts,  while  the  under  half  is  sharply  constricted. 

The  cavity  is  completed  by  extension  of  the  reticulating  degeneration 
downward,  particularly  upon  the  periphery,  and  by  the  ballooning  and 
detachment  of  the  deeper  cells;  the  latter  subsequently  become  trans- 
formed into  the  compressed  bands  which  traverse  the  lower  portion 
of  the  pock. 

Umbilication. — Exceptionally  a  sort  of  umbilication  may  result  from 
the  accidental  piercing  of  the  centre  of  the  pock  by  a  hair  follicle,  the 
cornified  neck  of  which  limits  the  swelling  of  the  prickle  cells.  The 
characteristic  depression  in  the  centre  of  the  vesicle  is  due,  however, 
to  another  cause.  It  is  the  result  of  the  reticulating  degeneration  and 
oedematous  swelling  of  the  cells.  These  occur  chiefly  at  the  periphery, 
whereas  the  ballooning  degeneration  which  occurs  slowly  and  gives  rise 
to  less  swelling  takes  place  in  the  centre.  The  umbilication  is,  therefore, 
due  rather  to  a  bulging  of  the  periphery  of  the  vesicle  than  to  a  retraction 
of  the  centre. 

The  pressure  of  the  lateral  oedematous  cells  is  so  great  as  to  lead  to 
obliteration  of  the  underlying  papillae,  while  in  the  centre  of  the  pock, 
before  suppuration  begins,  they  not  only  persist  but  project  into  the 
cavity  of  the  pock. 

During  the  vesicular  stage  the  dilatation  of  the  papillary  bloodvessels 
beneath  the  pock  is  slight  and  the  emigration  of  leukocytes  is  strikingly 
small.    A  dense  collection  of  plasma  cells  is  seen  in  the  sheaths  of  the 


Tiii<:  PAT  1101/ )(:y  of  ,smaijj>ox  24r> 

vessels  and  increases  in  niiniherjis  (Jic  vcsific  mnliircs.  'I'liis  jilxind.'ince 
of  plasma  cells  is  remarkable,  considering  the  acuteness  of  the  process, 
and  is  otdy  foniid  among  the  pock-lik(^  processes  in  variola  itself. 

After  the  fiftli  day,  the  bloodvessels,  snpcrficial  and  deep,  become 
distinctly  dilated  and  a  stream  of  leukocytes  is  poured  out,  doubtless 
attracted  by  the  dead  germs  in  the  tissues.  The  margin  between  the 
corimn  and  epidermis  is  so  densely  packed  as  to  be  scarcely  recognizable. 
'I'he  cavity  of  the  pock  gradually  fills  uj)  completely  with  these  white 
l)l()od  cells.  If  the  horny  roof  holds,  the  mass  is  converted  almost 
into  solid  tissue;  if  it  ruptures,  there  is  morcor  less  profuse  suppiinition, 
leading  to  the  formation  of  crusts. 

The  primary  pustulation  is  due  to  the  variolous  j)oisoii,  but  pro- 
longed suppuration  must  l)e  ascribed  to  secondary  ])yogenic  infection. 

Healing. — Even  before  the  contents  of  the  pustule  are  completely 
dry,  a  thin  layer  of  epithelial  cells  lying  close  on  the  connective  tissue 
extends  from  all  sides  under  the  pustule. 

When  the  scab  is  thrown  off  there  is  displayed  a  persistent  trough-like 
depression.  Where  the  scab  does  not  to  any  great  extent  depress  the 
base  of  the  pock,  the  papillary  layer  is  not  completely  flattened  out,  and 
the  scar  is  not  so  deeply  excavated. 

"  The  depth  of  the  scar  consequently  depends  on  the  degree  and 
duration  of  the  flattening  of  the  base  of  the  pock  beneath  the  pustule 
and  the  scab,  and  we  see  therefore  that  the  rational  treatment  to  avoid 
scars  should  be  mainly  directed  to  the  aborting  of  the  pustular  stage 
and  the  rapid  removal  of  the  scab  by  profuse  epithelial  new-growth. 
.  .  .  .  Suppuration  alone  causes  no  necrosis  of  the  papillary  body, 
but  it  may,  if  profuse,  lead  to  a  more  rapid  casting  off  of  the  scab,  and  thus 
indirectly  to  the  freeing  of  the  base  of  the  pock;  the  profusely  suppurat- 
ing cases  of  smallpox  are  not  those  which  leave  the  worst  scars.  No 
doubt  prolonged  suppuration,  coupled  with  inappropriate  treatment, 
scratching,  etc.,  may  lead  in  many  cases  to  a  purulent  sequestration  of 
parts  of  the  cutis  and  thus  to  distinct  scar  formation." 

For  a  long  time  the  bloodvessels  and  all  the  lymph  spaces  of  the  cutis 
are  dilated,  and  wandering  cells  and  pigment  are  more  abundant  than 
normal. 

The  pocks  upon  the  'palms  of  the  hands  and  soles  of  the  feet  develop 
in  a  somewhat  difi^erent  manner  from  those  elsewhere.  The  reticulating 
and  ballooning  degenerations  are  only  imperfectly  seen  here. 

The  "pock  body"  is  usually  fan-shaped,  undergoes  a  drier  degener- 
ation, and  has  a  horny  character.  It  is  usually  more  superficially  situated 
in  the  epidermis. 

Stokes^  believes  that  "the  primary  exudation  of  plasma  cells  has  not 
been  sufficiently  emphasized  by  Unna.  These  plasma  cells  are  probably 
derived  in  part  from  proliferation  of  the  endothelial  lining  of  the 
lymph  spaces  and  bloodvessels.  In  some  sections  made  from  very  early 
cases,  the  epithelial  cells  do  not  show  any  great  injury,  but  the  cutis 

1  The  Palliology  of  Smallpox,  Johns  Hopkins  Bull.,  Xo.  1-19.  Aug.,  1903. 


246  SMALLPOX 

is  swollen  and  there  is  increased  number  of  plasma  cells  in  the  lymph 
spaces  and  around  the  small  bloodvessels.  The  condition  resembles  the 
response  to  some  injury  and  seems  to  be  the  first  change  in  the  skin, 
since  the  various  changes  in  the  epithelial  cells  are  not  yet  present." 

In  a  hemorrhagic  case  Stokes  found  the  capillaries  and  lymph  spaces 
greatly  distended  and  numerous  hemorrhages  present  in  the  connective 
tissue. 

Quite  recently  careful  and  extended  studies  of  the  pathology  and 
etiology  of  variola  have  been  carried  on  by  Prof.  Councilman/  of  Harvard 
College,  and  a  number  of  his  associates. 

The  anatomy  and  histology  of  variolous  lesions  were  investigated 
by  Councilman,  Magrath,  and  Brinckeroff.  Eight  sets  of  complete 
serial  sections  were  made  through  typical  vesicles  and  pustules.  In  the 
main  Unna's  findings  are  confirmed,  but  some  new  facts  concerning 
the  histology  of  the  pock  are  presented. 

The  earliest  form  of  degeneration  is  said  to  take  place  in  the  nuclei 
of  the  cells  of  the  rete  mucosum.  They  become  swollen,  more  vesicular, 
and  exhibit  an  increased  central  clumping  of  the  chromatin.  In  the 
lesions  leading  to  vesicle  formation  there  is  a  reticular  degeneration  of 
the  cytoplasm,  with  a  more  advanced  degeneration  of  the  nucleus.  The 
nuclei  may  lose  their  form  and  become  irregular  and  shrivelled,  assuming 
peculiar  shapes.  Advanced  forms  of  cytoplasmic  inclusions  are  common 
in  the  nuclear  space  and  in  vacuoles  in  the  protoplasm.  The  proto- 
plasmic processes  connecting  the  cells  disappear,  but  the  periphery  of 
the  cells  remains  and  undergoes  condensation. 

It  is  this  degeneration  which  causes  the  peculiar  reticular  appearance 
of  the  early  vesicle.  It  is  always  better  seen  in  the  periphery  than  in 
the  centre  of  the  vesicle.  With  the  increase  of  the  exudate  coming  from 
below,  the  spaces  within  the  cell  enlarge,  finally  rupture,  and  a  network 
is  formed  by  the  coalescence  of  the  cell  borders.  The  typical  small 
vesicle  is  always  fan-shaped,  with  the  handle  of  the  fan  seated  upon  the 
corium. 

A  later  form  of  degeneration,  the  ballooning  degeneration  of  Unna, 
may  best  be  regarded  as  a  hyaline  fibrinoid  degeneration.  The  Mal- 
pighian  cells  become  swollen,  lose  their  granular  character,  become 
homogeneous  and  refractile,  and  stain  more  intensely  with  the  acid 
dyes. 

The  fluid  exudate  begins  early,  and  in  most  cases  simultaneously 
with  the  degeneration.  In  the  smallest  visible  papule  the  swelling  is 
due  chiefly  to  the  presence  of  exudate;  in  no  case  was  degeneration 
found  without  evidence  of  exudation.  The  early  exudate  is  clear  and 
contains  no  admixture  of  cells.  Indeed,  a  conspicuous  feature  of  the 
smallpox  process  everywhere  is  the  paucity  of  cells  in  the  exudate. 
The  cells  appear  only  at  a  late  stage  of  the  process,  and  are  much  less 
than  in  other  deo:enerations  and  exudations  due  to  bacterial  infection. 


1  Studies  on  the  Pathology  and  Etiology  of  Variola  and  Vaccinia ;  from  the  Sear  Pathological 
Laboratory,  Harvard  Medical  School ;  published  in  the  Journal  of  Medical  Research,  February,  1904. 


THE  IWTIIOI/XIY  OF  SMALLPOX  247 

It  seems  probable  that  tlie  cells  appear  when  the  ^m-W'w  cli.'inu-ter 
of  the  process  is  passed,  they  being  then  attracted  to  the  necrosis. 
Did'erent  viirictics  of  leukocytes  are  present,  but  the  polynuclcir  neutro- 
nhilcs  prc<h)niiiiui('.  In  the  lat<!  lesions  there  are  accurniilutions  around 
iiie  vessels  of  the  varieties  of  lynij)hoid  cells  which  nrc  sf)  proniirifiit  in 
lesions  in  the  internal  organs,  and  which  Unna  has  indentificd  as  plasma 
cells. 

During  the  process  of  repair  the  contents  of  the  pustule  undergo 
condensation  from  the  cvaponition  or  absorption  of  flic  fhiid,  bcc-oniirig 
finally  changed  into  a  solid  granular  mass  in  which  iifjthing  can  be  rec- 
ognized. A  complete  regeneration  without  cicatrization  is  possible  when 
the  lesions  are  not  extensive  and  do  not  involve  the  entire  epithelium, 
and  also  when  the  entire  epithelium  is  destroyed  over  a  small  area  only, 
the  papillary  bodies  remaining  intact.  When  destructive  changes  in 
the  corium  occur,  complete  regeneration  cannot  take  place.  After 
recovery  the  papillae  are  absent  or  very  imperfectly  developed  and  the 
connective  tissue  beneath  has  the  characteristics  of  cicatricial  tissue. 

Councilman,  Magrath,  and  Brinckerhoff  believe  that  Weigert's 
explanation  of  the  cause  of  the  umbilication  is  correct  in  many  instances. 
Weigert  regarded  the  umbilication  to  be  due  to  the  diphtheroid  degen- 
eration of  the  epithelium  of  the  centre  of  the  vesicle,  thus  preventing 
the  distention  of  the  centre  by  the  exudate;  he  believed,  however,  that 
the  hair  follicles  and  sweat  ducts  also  played  a  part  in  its  formation. 
The  above-mentioned  investigators  cannot  attribute  the  umbilication 
to  any  single  cause.  In  serial  sections  the  presence  of  hair  and  sweat 
glands  at  the  point  of  umbilication  was  rarely  missed.  The  hair  follicles 
play  a  more  important  role  than  the  sweat  glands.  Nevertheless,  they 
are  not  exclusive  agents  in  the  umbilication,  for  lesions  are  frequently 
present  upon  the  glans  penis.  It  is  suggested  that  two  factors  may 
combine  to  favor  umbilication :  a  naturally  more  resistant  centre  (doubt- 
less due  to  the  degenerative  changes),  and  in  some  cases  the  presence 
of  a  hair  follicle  or  duct  which  further  strengthens  the  centre. 

Histology  of  Purpura  Variolosa. — The  skin  of  four  cases  of  purpuric 
variola  was  examined  by  Councilman,  Magrath,  and  Brinckerhoff. 
Although  diffuse  hemorrhages  were  present,  the  skin  almost  everj'where 
showed  the  early  changes  characteristic  of  the  variolous  process.  The 
general  condition  was  that  of  swelling  and  reticular  degeneration  of  all 
of  the  lower  cells  of  the  epidermis.  There  were  large  vacuoles  in  the 
cells,  but  rarely  spaces  between  the  cells  resulting  from  their  rupture. 
In  the  Malpighian  layer  there  was  some  separation  of  the  cells  by  the 
exudate,  and  in  one  section  the  entire  epidermis  over  a  small  area 'was 
separated  from  the  corium.  The  nuclei  were  degenerated,  shrunken, 
and  lay  in  large  spaces. 

The  corium  showed  dilatation  of  the  bloodvessels,  and  hemorrhages, 
chiefly  in  the  papillary  layer.  The  most  striking  condition  found  in  the 
corium  was  the  presence  of  large  numbers  of  streptococci  in  the  blood- 
vessels and  lymphatics  and  in  the  tissues.  No  polynuclear  leukocytes 
were  found  in  the  epidermis,  and  but  few  in  the  corium. 


248  '  SMALLPOX 

Mucous  Membranes. — As  has  been  stated  in  the  chapter  on  symptom- 
atology, certain  of  the  mucous  membranes  participate  in  the  variolous 
process  and  show  the  presence  of  pocks.  In  general  terms  it  may  be 
said  that  most  of  the  mucous  surfaces  to  which  air  has  free  access  may 
show  smallpox  lesions.  The  nasal,  lingual,  buccal,  and  pharyngeal 
surfaces  commonly  show  an  abundance  of  lesions.  The  oesophagus 
often  contains  pocks,  but  seldom  in  its  lower  third.  At  autopsy  these 
lesions  often  appear  as  slightly  excavated  ulcers,  frequently  with  attached 
blood  clots. 

Although  a  few  of  the  older  writers  have  described  pocks  in  the 
stomach  and  intestines,  it  is  extremely  doubtful  whether  they  occur  in 
these  regions.  We  have,  in  a  number  of  instances,  seen  small,  punctate 
hemorrhages  in  the  gastric  mucosa,  and  in  one  case  a  small,  superficial 
ulcer,  but  never  any  genuine  variolous  lesions.  A  catarrhal  condition 
of  the  gastric  and  intestinal  mucous  membrane  is  not  rare.  Follicular 
ulcerations  in  the  intestines  have  doubtless  been  mistaken  by  some 
observers  for  smallpox  lesions. 

About  the  anus  and  a  little  higher  in  the  rectum  the  remains  of 
pustules  are  said  to  be  occasionally  observed.  This  must,  however,  be 
rare,  as  Perkins  and  Pay  in  forty  carefully  performed  autopsies  failed 
to  find  any  pocks  in  these  regions.  The  bladder  and  urethra  are  always 
free  of  lesions,  with  the  exception  of  the  meatus  urinarius. 

Councilman,  Magrath,  and  Brinckerhoff ,  from  a  careful  study  of  the 
various  membranes  in  smallpox,  conclude  that  "the  lesions  of  the 
mucous  membranes  are  in  degree  proportional  to  the  extent  and  to  the 
severity  of  those  of  the  skin.  At  an  early  stage  of  development  they 
resemble  the  lesions  of  the  skin,  but  owing  to  the  structure  of  the  mucous 
membrane  the  resemblance  is  lost  in  the  course  of  their  evolution.  In 
the  absence  of  a  restraining  horny  layer,  the  degenerated  epithelial  cells 
are  cast  off  and  the  vesicle  within  the  epidermis  is  rarely  seen,  the 
pustule  never." 

The  respiratory  tract  is  more  attacked  than  any  of  the  internal  surfaces. 
The  larynx,  as  is  known,  is  often  severely  involved.  Pustules  and  ulcers 
are  often  found  in  the  trachea,  particularly  at  the  division  of  the  bronchi. 
They  may,  moreover,  be  encountered  in  the  bronchial  tubes  of  the 
third  and  fourth  order.  The  small  bronchi  often  exhibit  in  addition 
a  catarrhal  process,  with  necrosis  of  the  surface  epithelium  and  fibrinous 
or  purulent  inflammation.  The  lungs  not  infrequently  show  small  areas 
of  catarrhal  pneumonia. 

Curschmann  aptly  says  that  "true  pocks  on  serous  membranes  are 
fables  belonging  to  antiquity,  but  congestion,  inflammation,  and  ecchy- 
moses  are  common." 

The  meninges  and  the  peritoneum  seldom  exhibit  pathological  changes, 
but  the  pleural  surfaces  are  not  infrequently  inflamed. 

Stokes^  in  one  case  found  the  pleural  surfaces  dotted  with  abundant 
vesicles  about  the  size  of  number  six  shot.     On  microscopic  exami- 

1  Loc.  cit. 


TIIFj  PATIIOI/XIY  OF  SMAfJJ'OX  240 

iial.ioii   tlicy  ii])|)oarc(i   to   he  \ii\-'^(\  lyrnpli  spjifcs  (li.stftHlc<l  with   serous 

(liiid. 

The  solid  abdominal  vifircra  iindcrifo  serious  Jiiteriiliou  of  struf.-ture. 
The  liver  m  fatal  cases  of  suiallpox  is  uciirly  always  eular^ed,  the 
iuerease  iu  si/e  iu  souic  cases  heiu^  uiost  prououuced.  The  surface  of 
the  orrran  and  the  hej)atic  tissue  upon  incision  exhihit  a  coloration  much 
j>aler  than  normal.  Nearly  all  writers  refer  to  degenerative  changes  in 
the  liver  varying  from  cloudy  swelling  to  a  more  or  less  intense  fatty 
deceneriition.  Weigert  descrihes  areas  of  local  coagidation  necrosis 
in  which  are  seen  nuclear  detritus  and  many  degenerated  cells  without 
nuclei.  Siderey  says  there  is  intense  congestion  with  migration  of  white 
blood  corpuscles  and  swelling  of  the  endothelial  lining  of  the  capillaries; 
later  the  liver  cells  swell  and  undergo  fatty  degeneration. 

Roger  and  (larnier'  made  a  microscopic  study  of  the  liver  in  seventeen 
smallpox  cases.  They  conclude  that  variolous  hepatitis  is  usually  total 
and  may  affect  the  interstitial  or  parenchymatous  tissue.  P'atty  hepatitis 
is  said  to  be  the  most  common,  having  been  found  in  six  out  of  eleven 
cases  of  coherent  or  confluent  smallpox.  In  hemorrhagic  smallpox,  it 
is,  according  to  these  investigators,  constant.  Necrotic  hepatitis  is  more 
rare  and  is  characterized  by  cellular  necrosis  in  limited  foci  or  diffuse 
bands.  This  condition  was  observed  alone  in  two  cases,  and  in  two 
others  associated  with  fatty  degeneration.  A  third  variety,  hemorrhagic 
hepatitis,  was  found  in  one  case  in  a  child  with  congenital  variola. 

Ponfick  and  Curschmaim  both  state  that  in  purpura  variolosa  the 
liver  is  normal  in  size  and  color  and  does  not  exhibit  the  degenerations 
above  referred  to. 

According  to  Ponfick,^  the  spleen  in  those  who  die  early  is  swollen, 
soft,  and  of  a  light-red  color.  It  later  resumes  its  normal  appearance 
except  in  purpura  variolosa,  in  which  variety  it  is  small,  hard,  and  dark 
red,  with  prominent  follicles. 

Roger  and  WeilP  found  the  spleen  hypertrophied  in  every  one  of 
sixteen  fatal  cases  of  confluent  smallpox.  Among  twelve  hemorrhagic 
cases  it  was  enlarged  in  four  instances.  The  most  interesting  micro- 
scopic changes  are  the  presence  of  nucleated  red  blood  corpuscles,  and 
a  predominance  of  mononuclear  leukocytes  among  the  white  cells. 

Perkins  and  Pay^  noted  hemorrhages  into  the  splenic  pulp  in  six  out 
of  forty  autopsies;  three  of  these  were  cases  of  purpura  variolosa. 

The  kidneys,  like  the  liver,  show  changes  var^nng  from  cloudy  swelling 
to  fatty  degeneration.  Arnaud^  made  histological  examinations  of  the 
kidneys  in  thirteen  cases  of  smallpox.  The  changes  were  briefly  of 
two  types — an  interstitial  cell  infiltration  and  lesions  of  the  epithelium 
of  the  tubules. 

Stokes"  has  recently  made  a  careful  study  of  the  kidneys  in  variola. 

'  Etude  aiiatom.  et  cliim.  du  foie  dans  la  variole,  Archiv.  de  mOd.  exper.,  September,  1901. 
-  Ueber  die  Auat.Veriinderungen  der  iiinern  Organen  bei  bemor.  u.  pust.  Variola,  Berl.  klin.  Woch., 
1872,  No.  42. 
^  Les  maladies  infectieuses,  Paris,  1902. 

■*  Tbe  Etiology  and  Pathology  of  Variola,  Journal  of  Medical  Research,  October,  1903. 
6  Revue  de  m^d.,  1S9S,  tome  xviii.  p.  392.  ^  Loc.  cit. 


250  SMALLPOX 

Extensive  changes  were  found  in  every  kidney  examined.  In  one  case 
an  acute  interstitial  nephritis  such  as  described  by  Councilman  in 
diphtheria  and  scarlet  fever  was  found.  In  one  very  malignant  case 
the  changes  noted  Avere  as  follows:  In  the  glomeruli  the  capillaries 
contained  clear  hyaline  material  within  the  lumen.  This  was  due  to 
an  actual  degeneration  of  the  endothelial  lining  of  the  glomerular 
capillaries.  At  times  the  hyaline  material  formed  a  large  crescentic 
mass  of  homogeneous  clear  material  in  the  capsular  space.  The  epithe- 
lium of  the  convoluted  tubules  was  swollen  and  the  cytoplasm  of  the 
cells  contained  numerous  granules.  In  many  of  the  cells  the  cytoplasm 
had  completely  degenerated  into  a  mass  of  clear  droplets  which  pro- 
duced hyaline  casts  in  the  lumen  a  of  the  tubules.  The  clear  droplets 
took  Weigert's  stain  for  fibrin.  The  adrenal  bodies  were  found  by 
Perkins  and  Pay^  to  frequently  show  well-marked  fatty  degeneration  of 
the  cells  of  the  medulla. 

The  heart  in  fatal  cases  of  confluent  smallpox  is  usually  relaxed,  soft, 
and  somewhat  enlarged.  Microscopically  the  changes  are  those  of 
cloudy  swelling  and  fatty  degeneration;  fragmentation  of  the  muscle 
fibres  is  commonly  seen. 

In  purpura  variolosa,  according  to  Ponfick,  the  organ  is  firm,  con- 
tracted, and  of  a  brownish-red  color. 

The  Lymphatic  Glands. — Roger  and  WeilF  state  that  hypertrophy 
of  the  glands  in  variola  follows  the  same  rule  as  splenic  enlargement; 
it  is  very  marked  in  the  pustular  variety  and  slight  or  absent  in  the 
hemorrhagic  form.  Microscopically  the  cells  found  are  similar  to  those 
seen  in  variolous  bone-marrow;  neutrophile  myelocytes  are  notably 
present  and  in  addition  there  are  some  basophile  myelocytes  and  occa- 
sionally eosinophiles.  Giant  cells  are  also  seen,  and  in  hemorrhagic 
smallpox  nucleated  red  blood  corpuscles. 

Stokes  examined  the  cervical  and  bronchial  glands  in  smallpox  and 
found  extensive  focal  necrosis  containing  an  abundance  of  streptococci. 

Bone-marrow. — In  1873  Golgi^  made  a  study  of  the  bone-marrow 
in  ten  cases  of  pustular  and  twenty-five  cases  of  hemorrhagic  smallpox. 
In  the  pustular  form  he  found  a  great  increase  of  the  white  cells,  while 
in  the  hemorrhagic  variety  he  found  a  great  increase  of  nucleated  red 
cells,  a  distinct  diminution  of  the  white  cells,  some  of  which  were  in 
process  of  fatty  degeneration,  and  diffuse  hemorrhages  in  the  medul- 
lary spaces.  The  medullary  tissue  was  red  and  almost  as  fluid  as 
blood. 

Chiari*  found  a  condition  which  he  designated  "osteomyelitis  vario- 
losa" in  72  per  cent,  of  twenty-two  cases  examined.  This  process  is 
characterized  by  pea-sized,  whitish,  grayish,  or  yellowish  nodules,  widely 
disseminated  in  the  marrow  substance.  These  consist  of  epithelioid 
cells  derived  from  proliferation  of  the  marrow  cells.    An  early  necrosis 

1  Loc.  cit.  -  Maladies  infectieuses,  p.  721. 

■*  Sulle  Alterazioni  del  Midollo  del  ossa  nel  variola,  Rlvisla  clinica  di  Bologna,  1873,  p.  238. 
*  Osteomyelitis  Variolosa,  Ziegler's  Beitriige  z.  pathol.  Anat.  u.  allgemein.  Pathol.,  1893,  Bd.  xiii., 
S.  13  ;  and  Zeitschrift  f.  Heilkunde,  Bd.  vii.,  S.  385. 


77//';  PATIIOhOaV  OF  SMALLI'OX  251 

sots  in.  C-liiiiri  rcf^iii-ds  these  focjil  nenr()S(!S  us  (lu(;  to  tlic  sj;ccifi(;  vari- 
olous ])oisoii. 

(!oiinnont  and  Montii<i;nani/  and  Rof^er,  Josu(^  and  Weill  have 
stndied  this  subject  with  results  wliieh  are  in  aeeord  with  those  above 
detailed. 

Rof^er^  says:  "'i'hc  cellular  fornuda  of  bone-marrow  in  variola  is  as 
follows:  (ireat  predominance  of  mononuclear  cells  and  relative  diminu- 
tion of  polynuclears."  The  cellular  findin<i;s  are  aiialofrous  to  those  of 
the  blood.  The  marked  dill'erences  noted  by  (lolf^n  in  the  marrow  of 
the  pustular  and  hemorrhagic  smallpox  were  not  confirmed  by  these 
writers. 

The  TesildcK. — The  occasional  occurrence  of  orchitis  variolosa  has 
led  to  a  careful  microscopic  study  of  the  structure  of  this  organ  after 
death, 

Chiari  found  pathological  changes  in  the  testicle  very  frequently 
among  the  cases  that  came  to  autopsy.  The  specific  variolous  change 
is  a  focal  necrosis  similar  to  that  observed  in  the  liver,  spleen,  kidneys, 
and  lymph  glands  by  Weigert.  Tlie  alteration  begins  early  in  the  course 
of  the  disease,  but  reaches  its  height  during  the  suppurative  stage. 
The  inflammatory  foci  are  said  to  be  located  predominantly  and  primarily 
in  the  interstitial  tissue,  although  Stokes,^  in  a  recent  examination  of 
two  cases  states  that  the  process  began  as  a  necrosis  of  the  epithelial 
cells  of  the  seminiferous  tubules. 

In  twenty-seven  examinations  of  the  testicles  Perkins  and  Pay^  found 
v^ell-marked  necrosis  in  eight.  Examination  of  the  ovaries  failed  to 
discover  any  lesions  of  this  character. 

The  brain  and  spinal  cord  ordinarily  exhibit  no  structural  alteration 
in  smallpox,  save  at  times  a  moderate  amount  of  congestion  and  oedema. 
In  a  small  proportion  of  cases  grave  changes  may  occur  even  in  mild 
cases.  To  this  attention  has  been  called  under  the  heading  of  Complica- 
tions of  the  Nervous  System. 

Hemorrhagic  Smallpox. — The  pathological  findings  in  hemorrhagic 
smallpox  differ  in  many  respects  from  those  in  ordinary  cases. 

The  condition  of  the  spleen,  liver,  and  kidneys  has  already  been 
referred  to.  It  is  uncommon  to  find  hemorrhages  in  such  viscera  as  the 
liver,  kidneys,  spleen,  brain,  etc.  On  the  other  hand,  the  bloody  extrav- 
asations are  very  common  upon  the  mucous  and  serous  structures  of  the 
body.  These  are  seen  as  ecchymoses  of  these  surfaces  and  as  free 
accumulations  In  the  cavities.  The  pleural  and  pericardial  sacs  not 
infrequently  contain  bloody  fluid  or  clots  and  less  commonly  the  peri- 
toneal cavity. 

The  loose  tissue  of  the  anterior  and  posterior  mediastina  and  the 
retroperitoneal  space  often  exhibit  bloody  exudates.  Hemorrhage  into 
the  kidney  structure  itself  is  extremely  rare,  but  it  is  seen  in  the  renal 
pelvis  and  beneath  the  capsule  of  the  kidney. 

'  La  moclle  osseuse  dans  la  variole.  XUI.  Internatioual  :Medical  Congress,  Section  on  General 
Pathology,  Paris,  1900. 
-  Les  maladies  infectieiises,  p.  700.  s  loc.  cit.  ■•  Loc.  cit. 


252  SMALLPOX 

Ecchymoses  may  occur  in  synovial  membranes  and  free  hemorrhage 
into  the  cavity  of  the  joints.  Ziilzer,  cited  by  Curschmann,  speaks  of 
the  frequent  occurrence  of  hemorrhages  into  the  sheaths  of  nerves,  but 
Wagner  could  not  corroborate  this  observation. 

As  might  be  naturally  expected  from  the  symptomatology  of  hemor- 
rhagic smallpox,  practically  all  of  the  mucous  membranes  may  be 
involved  in  the  hemorrhagic  process.  Bleeding  may  occur  from  any 
portion  of  the  alimentary  canal,  from  the  mouth  to  the  anus;  the  same 
is  true  of  any  part  of  the  respiratory  mucous  membrane,  from  the 
nostrils  to  the  lungs ;  hemorrhagic  infarcts  may  form  in  the  pulmonary 
tissue. 

Subconjunctival  hemorrhage  is  frequent  and  constitutes  a  conspicuous 
and  characteristic  early  symptom  of  purpura  variolosa. 

Bloody  extravasation  into  the  Fallopian  tubes  and  uterus  is  extremely 
common.  Hemorrhage  into  the  structure  of  the  testicles  and  ovaries  is 
rarely  seen,  although  the  Graaffian  follicles  of  the  latter  are  said  to  be 
occasionally  infiltrated  with  blood. 

Councilman,  Magrath,  and  Brinckerhoff^  classify  the  changes  occur- 
ring in  the  various  organs  and  tissues  in  smallpox  as  follows : 

A.  Lesions  in  character  and  in  distribution  fundamentally  specific 
and  due  to  the  presence  of  a  parasite  peculiar  to  the  disease. 

B.  Lesions  associated  with  the  above,  of  indeterminate  specificity,  in 
kind  analogous  with  those  present  in  many  of  the  infectious  diseases, 
but  in  degree  characteristic  of  variola. 

C.  Lesions  caused  by  accessory  etiological  factors,  bacteria  whose 
presence  and  activity  are  conditioned  by  the  specific  infection. 

Concerning  the  lesions  in  the  two  latter  groups  these  writers  sum- 
marize as  follows: 

\.  Proliferation  within  the  haematopoietic  organs  is  constant  and  well 
marked,  and  gives  rise  in  the  spleen,  the  lymph  nodes,  and  the  bone- 
marrow  to  the  formation  of  mononuclear,  basophilic  cells,  and  in  the 
lymph  nodes  and  the  marrow  to  phagocytic  endothelial  cells.  The 
former  pass  into  the  blood  in  large  numbers.  This  process  is  present 
to  some  degree  in  other  infectious  diseases,  but  is  here  so  prominent  as 
to  be  well-nigh  characteristic. 

2.  Cellular  infiltration  with  the  mononuclear  basophilic  elements 
above  mentioned,  focal  and  interstitial  in  distribution,  occurs  constantly 
in  the  testicle,  and  usually  in  the  kidney,  in  the  liver,  and  in  the  adrenal 
glands.  In  the  testicle  this  infiltration,  by  pressure  and  by  thrombosis, 
causes  anaemic  focal  necrotic  lesions,  which  seem  to  be  specific  of  the 
disease. 

3.  Degeneration,  focal  in  character,  apparently  not  anaemic,  but  due 
to  the  action  of  toxins,  and  leading  to  necrosis,  at  times  with  hemorrhage 
and  accompanied  by  focal  formation  of  phagocytic  cells,  is  present  in 
the  blood-forming  cells  of  the  bone-marrow,  and  constitutes  a  lesion 
almost  pathognomonic,  but  devoid  of  parasites.     Difl'use  degeneration, 

1  Journal  of  Medical  Research,  February,  1904. 


77//';  I'ArilOLOCY  OF  SMALLI'OX  25.", 

I,()xi('  ill  (;liiu';i,r(('r,  is  present  in  (Jk;  liver,  tlie  kidney,  llie  jidrcnMJ  ^'laii'l, 
and  the  testicle;  in  the  liver  cloudy  swellinji;  is  more  marked  than  it  is  in 
any  other  iieutc^  infectious  disease.  r)therwise,  the  de^encr.'ition  is  not 
to  he  (listin<i;nislie(l  from  that  due  to  bacterial  infection. 

I.  Inhihition  of  cell  did'erentiation  hy  the  MC-tion  r)f  toxins  is  evifjencer] 
in  the  I)onc-niarrow  in  the  absence  of  complete  transformation  of  ante- 
cedent cells  into  polynuclear  leukocytes,  and  in  the  testicle  in  the  absence 
of  spermato<renesis.  The  first  mentioned  is  a  condition  seernin/^ly 
peculiar  to  variola. 

f).  The  paucity  of  j)oIymiclear  leukocytes,  alike  in  the  specific  lesions, 
in  the  focal  degenerations,  and  in  the  bone-marrow,  is  a  condition  so 
common  and  so  pronounced  as  to  render  it  a  striking  peculiarity  of  the 
disease. 

The  toxins  of  extraneous  bacterial  infection  may  contribute  to  the 
production  of  acute  parenchymatous  degeneration  of  the  liver,  the 
kidney,  the  adrenal  gland,  and  the  testicle,  which  are  already  mentioned 
as  associated  lesions  of  the  disease. 

In  addition,  pyogenic  bacteria  may  cause  the  formation  of  boils, 
cellulitis,  abscesses,  erysipelas,  and  gangrene. 

The  Blood.  Red  Cells. — The  red  blood  corpuscles,  according  to 
llayem,^  undergo  greater  destruction  in  smallpox  than  in  any  other 
fever.  This  is  not  noted  until  after  the  permanent  subsidence  of  the 
fever.  The  diminution  in  the  number  of  the  red  cells  is  most  pronounced 
in  the  hemorrhagic  and  confluent  cases,  in  which  one  or  two  million 
erythrocytes  per  cubic  millimetre  may  be  lost  in  a  very  brief  period. 
In  hemorrhagic  smallpox  the  anaemia  comes  on  more  rapidly;  in  a 
patient  dying  on  the  seventh  day,  Hayem  counted  but  2,000,000  cor- 
puscles. There  is  likewise  a  reduction  of  the  hfemoglobin,  and  this  may 
be  apparent  before  the  cells  are  diminished  in  number.  During  the 
febrile  period  of  the  disease  the  red  cells  are  normal  or  increased  in 
number,  perhaps  due  to  concentration  of  the  blood.  Fibrin  is  increased 
after  suppuration  begins. 

White  Cells. — The  examinations  of  the  blood  with  reference  to  the 
leukocytosis  have  not  given  entirely  uniform  results  in  the  hands  of 
different  investigators. 

In  1870  Brouardel  described  the  existence  of  a  leukocytosis  in  the 
pre-eruptive  stage  of  the  disease  which  increased  during  the  development 
of  the  eruption  and  diminished  after  the  occurrence  of  pustulation.  In 
the  very  mild  and  in  the  very  malignant  cases  the  leukoc}i:osis  was  in 
abeyance. 

Verstraeten,  in  1875,  stated  that  the  leukocytosis  was  proportionate 
to  the  severity  of  the  disease,  and  was,  therefore,  most  marked  in  hemor- 
rhagic smallpox,  a  remark  that  has  not  been  verified  by  more  recent 
investigators. 

Hayem,  Halla,  and  Pee,  each  showed^that  there  is  a  leukoc^'tosis  more 
pr.less  projiounced  in  all  forms_of  thedisease. 

^  Du  saug  et  de  ses  alterations  anatomiques,  Paris,  1S99. 


254  SMALLPOX 

A  valuable  contribution  to  our  knowledge  of  the  subject  was  made 
by  Pick^  in  1893.  Forty-two  cases  representing  all  grades  of  severity 
were  examined.  He  demonstrated  more  or  less  leukocytosis  in  all  but 
the  mildest  cases.  In  mild  cases  the  leukocytosis  is  slight,  not  often 
exceeding  the  high  normal  limit.  In  severe  cases  it  is  demonstrable 
only  after  the  vesicular  stage  is  reached,  and  attains  its  maximum  about 
the  ninth  to  the  eleventh  day,  then  slowly  subsiding  unless  interrupted 
by  complications.  In  confluent  and  hemorrhagic  cases  the  leukocytosis 
according  to  Pick  is  insignificant  and  attributable  to  the  occurrence  of 
suppuration  or  complications. 

WeiP  examined  the  blood  of  twenty-four  cases  of  smallpox  of  various 
forms  at  intervals  of  a  few  days. 

Courmont  and  Montagnard^  studied  twenty  cases  of  smallpox, 
examining  the  blood  for  the  most  part  daily.  The  conclusions  of  Weil 
and  Courmont  and  Montagnard  differ  only  in  detail  and  are  herewith 
submitted  as  summarized  by  Ferguson:* 

Variola  is  (1)  always  accompanied  by  a  leukocytosis  characterized  by 
a  notable  increase  in  the  mononuclear  cells  of  small  and  medium  size. 
(2)  During  the  stage  of  vesiculation,  pustulation,  and  desiccation  alike, 
the  polymorphonuclear  leukocytes  are  proportionately  reduced  in 
numbers.  (3)  This  special  leukocytosis  is  accompanied  rarely  in  slight 
cases,  but  regularly  in  graver  cases,  by  the  appearance  in  the  blood  of 
cellular  types  not  normally  found  there,  namely,  (a)  intermediate  or 
transitional  forms  of  the  neutrophile  cells;  (h)  mononuclear  neutro- 
philes  (myelocytes) ;  (c)  nucleated  red  blood  corpuscles ;  {d)  mononuclear 
eosinophiles;  (e)  very  large  giant  forms  of  non-granular  mononuclear 
cells;  (/)  plasma  cells  (Weil).  (4)  In  hemorrhagic  cases  a  leukocytosis, 
if  present  at  all,  only  attains  feeble  proportions.  (5)  Cases  terminating 
fatally  are  characterized  by  more  or  less  abrupt  fall  in  the  number  of 
leukocytes. 

In  Weil's  cases  the  leukocytes  varied  in  six  cases  from  6000  to  10,000; 
in  thirteen  cases  from  6000  to  13,000;  they  exceeded  15,000  in  nine  cases, 
20,000  in  three  cases,  25,000  in  three  cases,  30,000  in  one  case,  and 
35,000  in  one  case. 

Ferguson'^  in  1903  made  a  careful  study  of  the  blood  of  sixteen  cases 
of  smallpox.  He  states  that  his  findings  are  substantially  in  accord 
with  the  results  obtained  by  Weil  and  Courmont  and  Montagnard. 
He  remarks  "that  the  feature  which  characterizes  the  leukocytosis,  in 
distinction  from  that  which  is  found  to  accompany  the  majority  of  the 
acute  exanthemata,  is  that  it  is  mononuclear  and  not  polymorphonuclear 
in  character.    In  other  words,  the  condition  is  one  in  which  the  smaller 

1  Untersuch.  ueber  das  qualitativen  Verhalten  der  Blutkiir.  bei  Variola,  etc.,  Arch.  f.Derm.  u.  Syph. 
Vienna,  1893,  Bd.  cv.  p.  63. 

2  These  de  Paris,  1901,  and  Etude  qualit.  et  quant,  de  la  leucocytose  variolique,  Compt.-rend.  Soc. 
de  bioL,  Paris,  June  23,  1901. 

3  La  leucocytose  dans  la  variole.  Compt.-rend.  Soc.  de  biol.,  Paris,  June  22, 1900,  p.  583  ;  ibid.,  June 
30, 1900,  Cong,  internat.  de  mfid.,  Paris,  1900,  p.  184. 

4  The  Leukocytosis  in  Variola,  Journal  of  Pathology  and  Bacteriology,  1903,  vol.  viii.  p.  411. 

5  Loc.  cit. 


77/ a;  I'ATiioLoay  <)i<'  smalli'ox  255 

mononuclear  elements  (inoliiding  the  lymphocytes)  are,  increased  ;it  tlif 
expense  of  the  polytnorphoniu-lcar  eloinonts. 

The  mononuclear  leukocytes,  in  a  scries  of  ci^'lil  milfl  nnd  discrete 
cases,  averaged  nearly  50  per  cent.,  and  in  some  cases  reached  60  per 
cent,  of  the  total  leukocytes.  Tn  more  severe  cases  the  mononuclears 
did  not  attain  the  level  reached  in  the  milder  cases.  In  the  most  severe 
cases  the  relative  and  absolute  increase  of  this  variety  was  to  a  certain 
extent  obscured  by  the  presence  in  the  blood  of  myelocytes  in  greater 
or  less  numbers — an  occurrence  which  accentuated  the  reduction  of  the 
polynuclears. 

The  eosinophile  cells,  according  to  Ferguson,  are  increased  both 
relatively  and  absolutely  in  the  earlier  stage  of  the  illness,  but  undergo 
a  distinct  reduction  at  a  later  period.  Eosinophiles  of  the  mononuclear 
variety  are  very  exceptionally  seen  and  only  in  the  most  severe  cases. 

In  severe  cases  they  are  found  in  the  blood  elements  normally  occur- 
ring in  the  bone-rnarrow  in  numbers  which  are  not  often  realized  in 
other  acute  mfectious  diseases. 

Magrath,  Brinckerhoff,  and  Bancroft^  have  recently  studied  the 
leukocyte  changes  in  fifty  cases  of  variola.  In  twelve  of  these  serial 
observations  were  made.  Four  cases  of  purpura  variolosa  were  included 
in  the  cases  studied. 

The  authors  find  a  greater  or  less  degree  of  leukocytosis  in  all  cases 
of  variola.  The  typical  case  of  severe  variola  vera  wdiich  recovers 
without  complications  presents  at  the  beginning  of  the  eruption  a 
normal  or  subnormal  count,  which  increases  with  the  development  of 
the  cutaneous  lesions,  then  suffers  a  slight  decline,  rises  again  during 
the  late  stage  of  the  eruption,  and  finally  falls  to  normal  during  con- 
valescence. Fatal  cases  often  show  a  high  leukocyte  count  in  the  early 
eruptive  stage,  but  then  a  gradual  fall  until  death.  ]Mild  cases  may 
show  no  rise  above  the  normal  limits  or  a  gradually  increasing  leukocy- 
tosis, reaching  its  acme  after  the  lesions  of  the  skin  have  passed  their 
active  stage. 

The  primary  and  secondary  hemorrhagic  forms  of  smallpox  both 
show  a  marked  hyperleukocytosis.  The  leukocyte  picture  in  variola  is 
characterized  by  an  increase  in  the  mononuclear  cell  types,  although 
the  minor  variations  in  the  leukocytic  curves  are  dependent  upon 
fluctuations  in  the  absolute  number  of  polymorphonuclear  neutrophiles. 

The  leukocyte  examination  is  considered  to  be  of  but  little  value  in 
either  diagnosis  or  prognosis. 

Bodies  in  the  Blood,  and  Infectiousness  of  the  Blood.— A  number  of 
investigators  have  found  motile  bodies  in  the  blood  of  persons  and 
animals  suffering  from  variola  and  vaccinia.  Anions;  these  may  be 
mentioned  Doehle  (1S92),  L.  Pfeiffer  (1S93),  :\Ionti  (1S94).  E.  Pfeiffer 
(1895),  Weber  (1896),  Walter  Reed  (1897),  Huguenin  (1897),  Roger 
and  Weill  (1900),  Dombrowski  (1902),  Roger  (1902),  and  ]Magrath  and 
Brinckerhoff  (1904). 

1  The  Leukocyte  Reaction  in  Variola,  Journal  of  Medical  Research,  February,  1904. 


256  SMALLPOX 

These  bodies  were  at  first  thought  to  be  pecidiar  to  variola,  but  later 
investigations  proved  them  to  be  present  in  other  conditions. 

Pfeiffer,  Reed  and  Stokes,  and  Wegefarth  point  out  that,  while  the 
granular  cells  described  by  them  are  most  readily  found  in  the  blood 
during  the  progress  of  certain  infectious  processes,  they  must  be  regarded 
as  normal  constituents  of  the  blood.  In  1896,  Miiller,  of  Vienna,  found 
constantly  in  freshly  drawn  blood  of  normal  and  diseased  individuals 
"small,  generally  round,  colorless  granules"  which  are  quite  distinct 
from  blood  plates. 

Magrath  and  Brinckerhoff^  have  recently  investigated  the  infectious- 
ness of  the  blood  in  smallpox.  They  conclude  that  bodies  widely  diverse 
in  size  and  somewhat  different  in  structure  occur  in  the  blood  of  patients 
with  variola,  and  in  that  of  the  monkey  inoculated  with  variola  virus. 
They  are  somewhat  more  numerous  during  the  secondary  fever  than 
at  other  times,  and  in  severe  than  in  light  forms  of  the  disease.  Bodies 
of  like  sort  are  occasionally  seen  in  the  blood  of  healthy  men,  in  that 
of  the  normal  monkey,  and  were  numerous  in  a  case  of  malignant  endo- 
carditis. These  bodies  do  not  admit  of  positive  identification  with  any 
known  form  of  cytoryctes  variolse.  They  may  be  accounted  for  as 
derivations  or  as  degeneration  products  of  blood  corpuscles,  as  blood 
platelets,  and  in  some  instances  as  erythroblasts.  The  blood  of  smallpox 
patients  inoculated  upon  the  cornea  of  the  rabbit  does  not  produce  a 
variolous  keratitis. 

THE  BACTERIOLOGY  OF  SMALLPOX. 

In  the  early  part  of  the  last  century,  Sacco  (1809)  found  in  vaccine 
lymph  certain  granules  usually  aggregated  in  masses  and  endowed  with 
independent  motion.^  For  over  half  a  century  no  further  investigations 
were  made  in  this  field.  In  1863  Beale  described  in  vaccine  lymph 
very  minute,  transparent,  hyaline  particles  which  he  regarded  as  the 
contagious  principle  of  the  disease. 

Chauveau  in  1868  added  greatly  to  our  knowledge  of  the  nature  of 
the  vaccine  lymph  by  demonstrating  that  the  production  of  vaccinia 
depended  upon  the  presence  of  its  contained  particles,  for  when  these 
were  removed  the  vaccine  lesion  could  not  be  induced.  He  also  showed 
that  the  activity  of  the  virus  was  not  interfered  with  by  considerable 
dilution.  Prof.  Burdon-Sanderson,  with  improved  technique,  confirmed 
the  work  of  Chauveau  concerning  the  sterility  of  vaccine  lymph  freed 
of  all  solid  particles. 

Cohn  in  1872  noted  certain  corpuscles  in  fresh  vaccine  lymph  to 
which  he  gave  the  name  micrococcus  vaccinae.  In  1873  Klebs  isolated 
from  vaccine  virus  micrococci  growing  in  tetrads,  to  which  he  gave  the 
name  of  tetracoccus  vaccinae. 

Koch  (1882)  and  Cornil  and  Babes  (1883)  also  noted  the  presence  of 

1  Loc.  cit. 

-  In  the  preparation  of  the  historical  aspect  of  the  bacteriology  of  this  subject  the  authors  have 
made  free  use  of  the  work  of  S.  Monckton  Copeman  on  Vaccination,  London,  1899. 


Till':  liACTKinoLoay  of  smalij'ox  257 

iiiicrococci,  llic  I'ornicr  in  \\\o.  vncciiic  vesicle  of  ;i  ehild.  (^iiist  in  1883 
grew  micrococci  on  artificial  nicdiji  and,  inocuhiling  calves  therewith, 
believed  that  in  some  cases  he  induced  true  vaccinia. 

Voigt  grew  three  species  of  bacteria  on  gelatin  j)Iatcs  from  vaccine 
lymph,  and  called  one  the  vaccinococens.  '^Jliis  was  found  consfjinfly, 
and  grew  in  pairs  and  fours.  Jnoculations  of  calves  were  chiimed  to 
render  them  immune  against  subsefpient  vaccination. 

Micrococci  were  isolated  from  vaccine  lymph  by  Guttman  0886), 
Marotla  (ISSH),  Meguin  (1880),  Buist  (1886),  and  Tenholt  (1887). 

In  1887  lllit.va  isolated  from  vaccine  lesions  the  streptococcus  pyogenes 
and  various  sta})liylococci.  Garre  in  1887  found  in  vaccine  lymph 
two  kinds  of  bacilli  and  a  coccus  which  he  regarded  as  specific.  The 
coccus  when  inoculated  upon  calves  was  said  to  produce  vaccine  vesicles 
followed  by  innnunity. 

In  1887  Pfeiffer  isolated  from  vaccine  lymph  a  variety  of  bacteria, 
including  a  yeast,  two  sarcin^e,  a  short  bacillus  allied  to  pi'oteus  vulgaris, 
and  certain  micrococci.  He  expressed  the  belief  that  the  causative  agent 
would  be  found  to  belong  to  the  sporozoa  and  not  to  the  bacteria. 

In  1889  Grigorieu  described  a  micrococcus  vaccinae  which  produced 
a  papular  eruption  in  calves  and  conferred  subsequent  immunity  against 
vaccination. 

In  1890  Woitow  isolated  four  staphylococci — aureus,  citreus,  cereus, 
and  albus.  He  mixed  cultures  of  these  and  claimed  therewith  to  produce 
typical  vaccinia  in  the  calf. 

Leoni  in  1890  and  Protopopoff  in  the  same  year  found  the  staphylo- 
coccus pyogenes  albus  and  micrococci. 

In  1891  Copeman  isolated  from  vaccine  virus  the  yellow,  white,  and 
orange  staphylococci.  None  of  these  microbes  were  regarded  as  the 
causative  agent.  Klein,  in  addition,  found  the  streptococcus  of  erysipelas 
in  human  vaccine,  the  use  of  which  was  supposed  to  have  occasioned 
an  attack  of  this  affection. 

In  1891  Crookshank  isolated  by  means  of  plate  cultures  a  large 
number  of  bacteria,  including  micrococci,  bacilli,  torula^,  etc.  He 
recognized  these  as  well-known  saprophytic  organisms  and  regarded 
none  of  them  as  specific. 

Besser  in  1893  cultured  the  lesions  of  smallpox  on  the  fifth  day 
and  obtained  a  growth  of  a  small  bacillus  which  he  regarded  as  the 
cause  of  the  disease. 

In  1893,  Straus,  Chambon,  and  jNIenard  obtained  numerous  colonies 
of  micrococci  when  gelatin  plates  were  inoculated  with  fresh  vaccine 
lymph,  with  or  without  glycerin.  It  was  found,  however,  that  when 
the  glycerinated  lymph  was  kept  for  a  considerable  period  the  number 
of  colonies  was  greatly  lessened. 

In  1893  x\nthony  found  four  kinds  of  micrococci  and  several  species 
of  bacilli  in  different  specimens  of  vaccine  lymph.  The  micrococci 
included  the  staphylococcus  pyogenes  aureus,  a  grayish-white  micro- 
coccus which  liquefied  gelatin,  a  yellow  micrococcus  which  did  not 
liquefy  gelatin,  and  an  organism  designated  the  "porcelain  micrococcus," 

17 


258  SMALLPOX 

which  was  invariably  present  in  fresh  vaccine  lymph.  The  bacilli  found 
were  the  bacillus  subtilis,  the  bacillus  mesentericus,  fluorescing  bacillus, 
and  a  motile  bacillus  growing  in  yellow  colonies;  all  of  the  organisms 
referred  to  were  regarded  as  impurities  save  the  "porcelain  micrococcus." 

Maljean  in  1893  noted  the  presence  in  vaccine  lymph  of  several 
micrococci,  including  a  peculiar  coccus  producing  brilliant-white  colonies 
on  different  media.  This  "coccus  vaccinae"  grew  as  isolated  points,  as 
diplococci,  and  in  short  chains.  It  gave  rise  in  calves  to  typical  vaccine 
lesions.     Subsequent  observers  failed  to  confirm  the  above  claims. 

Klein^  described  an  extremely  minute  bacillus  occurring  during  the 
early  development  of  vaccine  and  variolous  lesions.  It  was  found  in 
smallpox  virus  during  the  third  or  fourth  day  and  in  calf  lymph  seventy- 
two  to  ninety-six  hours  after  vaccination.  Clear  lymph,  collected 
aseptically,  was  spread  on  a  cover-glass,  heated,  treated  with  30  per 
cent,  acetic  acid  for  some  minutes,  and  then  subjected  to  prolonged 
staining  in  alcoholic  gentian  violet.  Bacilli  were  present  in  abundance 
in  the  calf  lymph  and  to  a  less  extent  in  variolous  material.  Lymph 
from  lesions  five  or  six  days  old  showed  no  bacilli  or  only  a  few  here 
and  there.  Spore-like  bodies  were  demonstrated  in  a  few  of  the  bacilli. 
It  was  found  impossible  to  grow  these  organisms  upon  any  of  the 
ordinary  media. 

In  1894  Baillard  and  Anthony  published  the  result  of  their  work 
on  the  effect  of  glycerination  of  vaccine  lymph  upon  the  number  of 
contained  bacteria.  Baillard  found  a  white  staphylococcus,  a  yellow 
staphylococcus,  and  the  bacillus  subtilis  quite  uniformly  present  in 
lymph.  He  concluded  from  his  experiments  that  glycerination  con- 
siderably diminished  the  number  of  bacteria,  but  did  not  destroy  all. 
The  bacillus  subtilis  and  the  staphylococcus  albus  were  still  living  after 
a  period  of  seven  months. 

Leoni,  in  1894,  working  along  similar  lines,  found  that  the  germs 
usually  present  in  vaccine  lymph  were  destroyed  by  the  glycerin  in  from 
one  to  four  months. 

In  1895,  Landmann,  prompted  by  the  prevalence  of  excessively  sore 
arms  among  children  in  Germany,  investigated  the  bacterial  content  of 
the  lymphs  distributed  from  thirteen  German  institutes.  He  found  that 
the  number  of  germs  in  the  different  lymphs  varied  from  50  to  no  less 
than  2,500,000  per  cubic  centimetre.  Among  the  microbes  isolated 
were  the  streptococcus  pyogenes,  the  staphylococcus  albus,  and  the 
staphylococcus  aureus. 

Dr.  Stephen  C.  Martin  and  Prof.  Ernst,  of  Boston,  in  1895,  isolated 
a  bacillus  from  vaccine  lymph  which  they  regarded  as  the  cause  of  the 
disease.  The  bacillus  was  short  and  thin  and  grew  only  on  ox  or  horse 
serum.  The  growth  was  of  a  white  color;  the  organisms  formed  chains 
and,  under  certain  circumstances,  appeared  as  a  micrococcus.  With 
the  fourteenth  generation  of  this  microbe  a  vaccine  vesicle  was  produced 
on  the  arm  of  an  infant  in  one  attempt  out  of  ten;  better  success  was 
attained  with  inoculation  of  calves. 

'  Report  of  tbe  Medical  Officer  to  the  Local  Governmeut  Board  for  1892-98, 


77//';  liACTKR,l()[J)(lY  OF  SMAfJJ'OX  250 

In  1895  \jV  Dilutee  found  in  vjictcine  lynipl)  .st;i|)liylocr)fci  rchiff;*!  to 
the  onJiiiiiry  pus  ori^anisnis.  Those  isolated  I'rotn  e;df  lynipli  li;if| 
different  chariw^teristies  from  those  obtained  from  hnm;ui  lymph;  tin; 
former  liquefied  blood  serum,  while  the  latter  did  no(. 

Tn  180(1,  Arloin^,  after  failing  to  establish  the  specifieity  of  the  or^nt]- 
isms  found  in  the  vaeeine  lym[)h,  eoneluded  that  (he  virulent  a^ent  of 
vaccinia  must  be  a  soluble  toxin.  From  experimentally  induced  horse- 
pox  he  isolated,  with  great  care,  a  micrococcus  which  failed  to  produce 
vaccinia  in  the  human  subject  and  was  also  without  immunizing  effect. 
Boureau  and  Chaimiier,  in  1800,  in  an  examination  of  vaccine  lymph, 
fomid  a  variety  of  microbes,  including  the  staphylococcus  aureus,  cereus, 
and  albus,  micrococcus  flavus,  bacillus  subtilis,  bacillus  luteus,  bac- 
terium termo,  proteus  vulgaris,  a  cladothrix,  a  fluorescing  bacillus,  and 
several  other  unidentified  bacilli.  These  observers  gave  expression  to 
the  extraordinary  opinion  that  the  activity  of  the  lymph  was  related  to 
the  presence  of  the  staphylococci. 

In  reply  to  this  contention  Menard  in  the  same  year  again  emphasized 
the  statement  made  by  Copeman,  and  by  Straus  and  himself,  that  the 
microbes  that  can  be  isolated  from  the  lymph  are  in  no  way  essential 
to  its  specific  action,  and  that  its  potency  may  be  perfectly  preserved, 
even  though  the  micrococci  are  completely  destroyed  by  glycerination. 
Sacqueped  in  1896  found  in  various  specimens  of  vaccine  lymph 
three  species  of  staphylococci,  the  bacillus  subtilis,  the  bacillus  mesen- 
tericus,  and  an  unidentified  bacillus.  The  presence  of  the  bacilli  was 
considered  to  be  due  to  accidental  contamination. 

Delobel  and  Cozette  (1896-97),  in  collaboration  with  Gourny,  con- 
cluded that  the  organisms  most  constantly  found  in  vaccine  lymph 
were  a  yellow  and  a  white  micrococcus.  The  bacillus  subtilis  and  the 
bacillus  mesentericus  were  often  found  when  adequate  care  was  not 
taken  in  the  collection  of  the  lymph. 

Paul  in  1896  made  an  extensive  investigation  of  the  bacteria  occur- 
ring in  vaccine  lymph.  He  emphasizes  the  fact  that  the  staphylococcus 
pyogenes  aureus  is,  of  all  microbes,  the  most  common  resident  of  the 
lymph.  Different  samples  of  the  lymph  contained  golden  staphylococci 
which  varied  greatly  in  resisting  power  and  virulence.  While  the  use 
of  a  lymph  containing  an  abundance  of  staphylococci  should  be  avoided, 
yet  the  employment  of  such  lymph  is  not  necessarily  accompanied  by 
suppuration. 

In  1897  Copeman  and  Blaxall  carried  out  an  exhaustive  series  of 
investigations  on  the  bacterial  flora  of  calf  lymph,  which  led  to  a  con- 
firmation of  views  previously  expressed,  that  calf  lymph  (or  rather 
vesicle  pulp)  contains  a  large  number  of  micro-organisms  which  are 
in  no  way  related  to  its  specific  activity.  Human  lymph,  on  the  other 
hand,  was  usually  found  to  contain  remarkably  few  microbes;  this 
might  have  been  due  to  the  fact  that  the  vesicle  pulp  was  not  removed 
in  the  latter,  as  in  the  case  of  calf  lymph.  Calf  lymph  carelessly  collected 
was  often  contaminated  with  numerous  saprophytes  common  to  dust,  in 
addition  to  certain  pathogenic  organisms. 


260  SMALLPOX 

A  large  number  of  specimens  of  lymph  showed  one  or  more  of  the 
following  organisms.  The  appended  list  shows  the  germs  in  the  order 
of  their  prevalence  and  predominance. 

1.  Staphylococcus  cereus  flavus;  staphylococcus  cereus  albus  (Basset). 

2.  Large  yeast,  orange  colored;  small  yeast,  light-brown  color;  small 
yeast,  pale-salmon  color,  and  growing  very  slowly. 

3.  Staphylococcus  pyogenes  albus  (Rosenbach). 

4.  Staphylococcus  pyogenes  aureus  (Rosenbach). 

5.  Staphylococcus  pyogenes  citreus  (Basset). 

6.  Bacillus  mesentericus  vulgatus. 

7.  Bacillus  subtilis. 

8.  Moulds — penicillia,  mucors,  aspergilli:  sarcinee — lutea,  aurantiaca. 
One  or  more  members  of  groups  one  and  two  were  always  present. 

The  white  staphylococcus  was  frequently  present  and  the  golden  coccus 
rather  less  often.  The  bacillus  subtilis  and  mesentericus  were  accidental 
contaminations.  The  former  rarely  occurred  if  the  skin  was  cleansed 
thoroughly  and  the  lymph  collected  carefully. 

All  of  these  examinations  were  made  of  lesions  produced  by  calf-to- 
calf  vaccination.  When  one-month-old  glycerinated  lymph  is  used  on 
calves,  remarkably  few  colonies  of  extraneous  germs  are  found  in  the 
lesions  produced. 

If  a  drop  of  fluid  be  removed  from  an  early  vaccine  vesicle  of  a  healthy 
infant  or  calf  under  aseptic  precautions,  it  will  often  be  found  to  be 
sterile  as  far  as  any  organisms  cultivable  upon  ordinary  media  are 
concerned.  Such  lymph,  nevertheless,  will  give  rise  to  typical  vaccine 
lesions  when  inoculated  upon  a  susceptible  individual. 

Copeman  and  Blaxall  state  that  the  presence  of  pyogenic  organisms 
in  vaccine  lymph  does  not  in  any  way  imply  that  the  lymph  is  purulent 
and  that  inoculation  of  the  same  would  lead  to  suppuration.  A  Berlin 
Commission  reports  that  of  eighteen  samples  of  lymph  examined,  but 
five  contained  staphylococci  which  were  pathogenic  for  small  animals. 
It  is  important  to  note  that  these  five  specimens  were  used  without  harm 
in  the  vaccination  of  children.  The  streptococcus  pyogenes  was  not 
found  once  by  the  Berlin  Commissioners  in  sixty  samples  of  lymph.  It 
is  not  so  uncommonly  found  in  human  lymph. 

Copeman  and  Klein,  in  1894,  concurrently,  though  independently, 
described  a  minute  bacillus  in  practically  pure  culture  in  specially 
stained  preparations  of  vaccine  lymph  taken  before  the  full  maturity 
of  the  vesicles.  These  bacilli  were  either  absent  or  present  in  scant 
number  in  mature  lymph;  it  is  suggested  that  in  the  latter  stages  they 
have  given  place  to  spore  formation. 

No  growth  was  obtained  upon  the  ordinary  nutrient  media.  Later 
Copeman  obtained  pure  cultures  of  this  organism  by  inoculating  the 
centre  of  hens'  eggs  with  variolous  crusts  rubbed  up  with  sterile  water. 
The  eggs  were  incubated  for  one  month  at  37°  C.  At  the  end  of  this 
time  the  ordinary  egg  contents  were  replaced  by  a  creamy  material 
which,  examined  on  cover-glasses,  appeared  to  contain  a  pure  culture 
of  the  small  bacillus.    Inoculation  of  calves  with  this  material  produced 


77//';  nA(!Ti<:ii[(>i/)aY  of  smallpox  261 

vaccine  lesions,  the  lyni])h  of  which  gave  tyj)ical  vesicles  when  tnms- 
I'erred  to  children. 

C'opeman  admits  that  the  results  of  these  interesting  exjxuirnents  are 
rendered  inconchisive  by  the  fact  that  the  calves  cin[)loycd  were  inocu- 
lated elsewhere  upon  the  body  with  ordinary  vjiccinc  lynijjh;  every 
precaution,  however,  was  taken  to  prevent  c(jntaniination  of  the  defined 
area  inoculated  with  the  egg  cuUure.  In  later  experiments  Copeman  and 
IJlaxall  succeeded  in  growing  the  small  bacillus  on  other  culture  media. 

In  1900  Nakanishi^  isolated  a  bacilhis  from  liuman  and  bovine 
vaccine  lymph  to  which  he  gave  the  name  of  "bacillus  variabihs  Iym[)ha' 
vaccinalis."  This  organism  belongs  to  the  pseudodi})hthcria  group  and 
exhibits  great  variations  in  size  and  form.  Inoculation  of  the  cornea 
of  rabbits  with  cultures  of  this  bacillus  produced  bodies  in  the  epithelial 
cells  which  were  said  to  closely  resemble  the  cytorrhyctes  variola;  of 
Guarnieri. 

In  the  same  year  Levy  and  Finkler^  independently  described  a  l^acillus 
found  in  vaccine  lymph  which  they  designated  "corynebacterium 
lymphse  vaccinalis."  This  organism  belongs  to  the  pseuflodiphtheria 
class  and  is  probably  identical  with  that  described  by  Nakanishi. 

Cause  of  Pustulation  in  Smallpox. — It  is  quite  definitely  estalilished 
that  the  suppuration  of  the  variolous  pock  is  the  result  of  the  causative 
agent  of  the  disease  and  is  not  due  to  secondary  infection  with  pyogenic 
organisms.  In  the  vesicular  and  even  in  the  early  pustular  stage  of  the 
eruption  the  lesions  will  commonly  be  found  to  contain  no  bacteria 
cultivable  upon  ordinary  media.  In  an  investigation  of  the  contents 
of  smallpox  vesicles  and  pustules'  we  found  33  out  of  34  cultures  of  lesions 
before  the  seventh  day  sterile.  Frequently  a  drop  of  pus  from  a  lesion 
was  placed  upon  a  nutrient  medium  and  incubated  without  any  visible 
growth  developing  whatsoever.  In  all,  cultures  were  made  from  82  lesions 
in  51  cases  of  smallpox;  of  this  number  64  cultures  remained  absolutely 
sterile. 

This  work  is  in  accord  with  most  of  the  investigations  upon  this 
subject. 

Perkins  and  Pay*  made  30  cultures  from  typical  variola  lesions  at 
all  of  the  various  stages  from  the  beginning  vesicle  to  the  full  develop- 
ment of  the  ripe  pustule.  These  were  all  negative  with  the  exception 
of  4 — 1  on  the  eighth  day,  1  on  the  ninth,  and  2  on  the  tenth  days  of 
the  eruption. 

After  the  seventh  or  eighth  day  of  the  eruption  various  bacteria, 
chiefly  streptococci,  may  be  found  in  the  lesions. 

The  Streptococcus  Pyogenes  in  Smallpox. — The  streptococcus  is 
commonly  found  in  the  late  pustules  of  smallpox  and  in  many  of  the 
cutaneous  complications,  such  as  boils,  impetigo,  abscesses,  erysipelas, 
gangrene,  etc. 

1  Centralbl.  f.  Bakt.  u.  Parasit.,  1900,  Bd.  xxvii.  -  Deutsche  med.  Woch.,  June  2S,  1900. 

3  A  Preliminary  Study  of  the  Contents  of  Variolous  Vesicles  and  Pustules,  Journal  of  the  Ameri- 
can Medical  Association,  1903. 
*  Journal  of  Medical  Research,  October,  1902. 


262  -  SMALLPOX 

After  death  streptococci  are  found  in  the  cutaneous  lesions  and  in 
the  blood  and  internal  organs  in  nearly  all  cases.  There  would  appear 
to  be  in  many  cases  an  agonal  or  post-mortem  diffusion  of  streptococci 
throughout  the,  tissues.  In  40  autopsies  on  smallpox  patients  made 
by  Perkins  and  Pay  streptococci  were  found  distributed  throughout  the 
body  of  38. 

Ewing^  found  streptococci  present  in  about  90  per  cent,  of  the  skin 
lesions  cultured  at  autopsy.  He  also  noted  the  presence  of  streptococci 
in  the  blood  after  death  in  every  one  of  29  cases  examined.  In  10 
cases  of  varying  severity  in  which  the  blood  was  cultured  during  life 
the  results  were  negative. 

Ai'naud^  found  streptococci  in  the  blood  during  life  in  2  cases  of 
hemorrhagic  smallpox. 

Perkins  and  Pay^  examined  the  blood  in  20  cases  of  smallpox  and 
found  streptococci  in  11  cases,  before  or  just  after  death. 

Omitting  the  varioloids  and  convalescents  and  considering  only  the 
more  serious  cases,  a  total  of  16,  with  streptococci  in  11,  or  69  per  cent. 

It  is  evident  from  the  above  investigations  that  the  streptococcus  is 
almost  constantly  found  in  fatal  cases  of  smallpox.  While  no  one  can 
seriously  entertain  the  idea  that  its  role  in  smallpox  is  causal,  it  is  so 
uniformly  present  that  some  writers  believe  it  bears  a  peculiar  relation 
to  the  disease  differing  from  most  secondary  infections.  It  should  be 
remembered,  however,  that  the  same  statement  might  be  made  with 
equal  force  in  referring  to  the  relationship  between  the  streptococcus 
and  scarlet  fever. 

Many  writers  regard  the  streptococcic  bacterisemia  as  the  most  frequent 
cause  of  death  in  smallpox.  Councilman*  says:  "As  the  result  of  the 
study  of  the  disease,  both  by  culture  of  the  lesions  and  organs  and  by 
microscopic  examination  of  tissues,  we  are  inclined  to  regard  bacterial 
infection  as  a  more  important  agent  in  bringing  about  a  fatal  termination 
than  the  specific  parasite The  bacteria  are  chiefly  strepto- 
cocci." 

Perkins  and  Pay,  and  likewise  Councilman,  suggest  that  the  strepto- 
cocci gain  entrance  to  the  circulation  through  the  bronchial  and  pul- 
monary mucous  membranes. 

Perkins  and  Pay  found  that  the  pathogenicity  of  the  streptococci 
isolated  was  markedly  different.  Some  of  the  strains  killed  rabbits  in 
two  or  three  days,  while  others  were  without  effect.  The  writers  suggest 
that  the  failure  of  antistreptococcus  serum  prepared  from  one  variety 
of  streptococcus  may  be  thus  accounted  for. 

Protozoa  in  Variola  and  Vaccinia. — Griinhagen^  in  1872  appears  to 
have  been  the  first  to  call  attention  to  the  presence  of  protozoa  in  variola 
and  vaccinia.  He  described  in  vaccine  lymph,  clear,  refractive,  sharply 
contoured  bodies  both  free  and  attached  to  leukocytes. 

1  Proceedings  of  the  New  York  Pathlogical  Society,  May,  1902. 

2  Rev.  de  m^d.,  1900,  p.  303.  ^  loc.  cit. 
*  Journal  of  Medical  Research,  February,  1904,  p.  358. 

5  Bemerkungen  Ueber  den  InfeclionstoflF  der  Vaccin  Lymphe,  Arch.  f.  Dermat.  u.  Sylph.,  1872, 
p.  150. 


77//';  i:.\(;ti<:i!I()I.(i(;v  of  smallpox  2r;.'i 

Renault  in  JSSI  described  j)e('iiliur  Ixxiics  which  he  hchc\cd  lo  lic 
parasites  in  the  epithelial  cells  of  variola  and  vaccinia. 

In  ](SS7  Van  ^qv  LoefP  found  in  a  han^inf^  drf)p  of  clear  vaccine; 
lymph  numerous  small,  round  bodies  endowed  with  arno-bf^id  nu>vement; 
later  he  discov(!r('d  the  s;ime  bodies  in  smallpox  pustules. 

L.  Pfeill'er  pul)lished  a  series  of  papers  be^^iiminf;  in  1887,  desciibin^ 
the  presence  in  variolous  and  vaccine  lymph  of  the  "monocystis  epithe- 
lialis,"  a  small,  unicellular,  rounded  body  which  he  re<^jirfled  as  the 
specific  cause  of  smallpox.  These  bodies  were  also  found  in  the  epithelial 
cells  of  the  Mal|)i<^hian  layer  and  were  said  to  multiply  by  division  an<l 
by  endogenous  spore  formation. 

In  1892  Guarnieri^  made  a  most  important  contribution  to  the  study 
of  protozoa  in  variolous  affections.  lie  found  in  the  epithelial  cells  of 
the  skin  in  smallpox  and  vaccine  vesicles,  and  in  the  cells  of  the  cornea 
inoculated  with  variolous  and  vaccine  virus,  certain  bodies  which  he 
designated  the  "cytoryctes  variolse"  and  the  "cytoryctes  vaccinae" 
respectively.  (The  name  has  reference  to  the  alleged  devouring  of 
epithelial  cells  by  the  parasite  and  to  the  formation  of  a  clear  space 
about  it.) 

Guarnieri  attempted  the  cultivation  of  these  protozoa  by  inoculating 
the  cornea  of  rabbits  and  guinea-pigs.  At  the  end  of  fifty  hours  the 
cornea  was  scraped  and  the  material  examined  in  aqueous  humor  in 
a  hanging  drop.  Small,  refractile  bodies  were  found  which  possessed 
amoeboid  movements.  Upon  section  of  the  cornea,  bodies  varying  in 
size  and  shape  were  found  in  the  deeper  layers.  Multiplication  was  said 
to  take  place  by  binary  division  and  by  gymnospore  formation.  Bodies 
exhibiting  a  mulberry  form  were  described. 

Monti  confirmed  Guarnieri's  findings  and  produced  specific  lesions 
in  the  cornea  by  inoculation  with  various  tissues  from  cases  of  smallpox. 

Ruffer  and  Plummer^  in  1894  described  the  parasite  as  a  small, 
round  body,  about  four  times  the  size  of  a  staphylococcus,  lying  generally 
in  a  clear  vacuole  in  the  protoplasm  of  the  epithelial  cells. 

Guarnieri's  work  has  since  been  confirmed  by  a  number  of  investiga- 
tors, including  Jackson  Clark  (1894),  von  Sicherer  (1895),  Ernst  Pfeiffer, 
Gorini,  Lebredo,  and  Wasielewski.* 

Wasielewski  inoculated  corneas  with  sterile  substances  and  various 
bacteria  and  yeasts  and  failed  to  produce  the  typical  inclusions  seen 
when  variolous  or  vaccine  material  was  employed.  He  carried  the 
latter  inoculations  from  eye  to  eye  for  a  number  of  generations  and 
produced  uniform  lesions.  From  the  thirty-sixth  generation  material 
was  taken  from  the  cornea  and  seven  children  vaccinated;  of  this  number 
six  out  of  the  seven  developed  typical  vaccine  lesions. 

Ferroni  and  Massari''  inoculated  the  cornea  of  rabbits  and  guinea-pigs 
with  croton  oil  and  India-ink  and  claim  to  have  produced  in  the  epithelial 

1  Monatsh.  f.  prakt.  Dermat.,  18S7,  No.  5,  Bd.  vi.  p.  1S9. 

-  Centralbl.  f.  Bakt.,  August  25,  1894.  ^  Britisli  Medical  Journal,  June  30, 1894. 

<  Centralbl.  f.  Bakt.,  1897,  Bd.  xxi.  p.  901 ;  and  Zeit.  f.  Hygiene,  1901,  Bd.  ssxviii.  p.  212. 

6  La  Riforma  Med.,  1894. 


264  SMALLPOX 

cells  numerous  small  bodies  apparently  identical  with  those  described 
by  Guarnieri.  They  believe  that  the  so-called  parasites  are  in  reality 
derived  from  the  nuclei  of  epithelial  cells  and  from  leukocytes. 

Salmon,^  after  a  careful  study  of  the  staining  reactions  of  the  bodies 
described,  likewise  opposes  the  views  of  Guarnieri.  He  says:  "The 
pseudoparasite  is  not  an  endogenous  formation;  it,  therefore,  of  necessity 
has  an  extracellular  origin,  and  the  little  mass  of  chromatin  can  have 
but  one  origin,  namely,  the  migratory  cells."  Copeman^  remarks:  "No 
one  can  fail  to  be  struck  with  the  truth  and  completeness  of  Salmon's 
explanation  of  the  facts  previously  observed." 

An  important  article  in  opposition  to  Guarnieri's  conclusions  was 
contributed  by  HiickeP  in  1898.  This  investigator  concedes  the  speci- 
ficity, inoculability,  and  immunizing  properties  of  the  lesions,  but  does 
not  regard  the  bodies  described  as  parasites.  After  a  painstaking  study 
he  regards  the  inclusions  as  specific  degenerative  changes  in  the  epithelial 
cells  induced  by  the  vaccine  and  variolous  virus. 

Councilman,*  basing  his  opinion  upon  his  own  extended  investigations 
and  those  of  his  associates,  regards  the  "cytoryctes  variolse"  as  the 
parasite  causing  smallpox.  The  bodies  occur  within  the  epithelial  cells, 
within  the  nuclei,  and  free.  They  do  not  occur  as  isolated  structures, 
but  follow  each  other  in  a  cycle  corresponding  with  the  cycle  of  develop- 
ment of  living  things.  In  the  different  cases  the  same  forms  are  found 
at  the  same  period  of  the  disease.  The  bodies  increase  rapidly  in  the 
lesions,  and  the  lesions  increase  in  extent  by  continuous  infection  of 
adjoining  cells. 

Councilman  states  that  in  vaccinia  the  same  forms  of  parasites  are 
found  as  in  the  cytoplasmic  cycle  of  variola.  The  intranuclear  forms, 
however,  have  never  been  seen  in  vaccinia.  There  is  some  difference 
in  vaccinia  in  the  size  and  in  the  rapidity  of  development  of  the  parasites 
in  the  different  tissues  and  in  the  different  animals.  "The  differences 
are  not  greater  than  will  be  shown  by  the  same  flowers  in  different 
gardens." 

Councilman  and  Tyzzer  both  discuss  the  dissenting  opinions  as  to 
the  parasitic  nature  of  Guarnieri's  bodies.  Their  derivation  from 
leukocytes,  red  blood  cells,  extruded  nuclear  material,  and  specific  cell 
degeneration  is  considered  and  the  negative  evidence  presented. 

Councilman  says  that  bodies  simulating  those  which  occur  in  smallpox 
may  be  found  as  accidental  products  in  a  number  of  conditions.  In 
these  there  is  no  complexity  of  structure,  such  as  is  found  in  most  of 
the  smallpox  bodies,  and  there  is  no  sequence  representing  growth 
development.  The  morphological  products  of  cytoplasmic  degeneration 
do  not  simulate  the  parasites.  The  cells  in  which  the  youngest  forms 
of  parasites  are  found  have  morphologically  normal  nuclei  and  cytoplasm. 
Moreover,  the  earliest  degeneration  in  smallpox  is  found  in  the  more 
superficial  cells  of  the  epidermis,  while  the  parasites  are  in  the  lower. 

1  Ann.  of  Pasteur  Inst.,  April,  1897.  -  Vaccination,  1899,  p.  123. 

^  Die  Vaccine  Korperchen,  Beitr.  z.  path.  Anat.,  Bd.  xxv.,  supplement. 
*  Journal  of  Medical  Research,  February,  1904. 


77//';  liACTI'UUOI/KlV  Oh'  SMALLI'OX  265 

The  intr;i,iiii('lo;u-  |)jt-ra,sites  arc  Uvss  '.\.\)\.  to  1)(;  fonfnscd  uilli  ;Kfif|cnt;il 
products  tlijiii  iU'e  (lie  (■yi,()|)lji,sniif.  'I'licy  arc  lourid  in  nuclei  in  wliir'ji 
there  is  no  clia,n<i;c  in  tlic  clirorniiiin  and  llicy  stnnd  in  no  relation  to  tlic 
chromatin. 

The  work  of  ('ouncilman  and  his  associates  leaiJs  liiin  to  say:  "We 
beheve  that  these  l)odies  in  vaccinia  and  in  variola  are  hving  things. 
Wc  sec  no  |)ossil)ihty  of  another  conchisioii.     .  .    Wc  have  constantly 

found  the  organism  in  connection  with  the  dcveloj»ing  lesions  of 
the  disease.  .  .  .  The  bodies  increase  in  size,  and  with  growth 
details  of  structure  appear  which  are  always  re[)eated,  and  for  which 
the  time  relation,  as  far  as  can  be  determined,  is  the  same.  At  the  end 
of  growth  a  form  of  multiplication  takes  })lace.  Ainrr-boid  motion  has 
been  made  out  in  the  vaccine  parasites  by  so  competent  aii  observer  as 
Wasielewski,  but  although  believing  that  the  bodies  are  parasites,  he 
very  properly  does  not  regard  this  as  proof.  .  .  .  This  view  that 
the  cytoryctes  variokie  is  the  cause  of  variola  must  for  the  present 
rest  on  the  fact  that  it  is  always  associated  with  the  lesions  of  the  disease, 
develops  further  as  the  lesions  develop,  and  is  found  under  no  other 
conditions." 

Calkins^  describes  the  life  cycle  of  the  variola  parasite  as  follows: 

The  first  development  of  the  germ  in  the  host  is  unknown;  it  probably 
takes  place  in  the  seat  of  primary  infection,  forming  an  organism  which 
reproduces  by  germs  or  "gemmules,"  the  process  being  known  as 
"multiplicative  reproduction."  The  gemmules  are  probably  carried 
in  the  blood  to  the  skin,  where  the  further  development  takes  place. 
The  gemmules  become  intracellular  (cytoplasmic)  amoeboid  organisms 
which  give  rise  to  similar  gemmules.  These  germs  penetrate  the  nuclear 
membrane  and  develop  into  gametocytes  (?),  one  forming  the  supposed 
male  gametes  and  the  other  the  female.  The  gametes  conjugate  ( ?) ;  the 
zygote  thus  formed  develops  into  a  comparatively  large  amoeboid 
organism,  in  which  the  pansporoblasts  originate.  These  pansporoblasts 
give  rise  to  primary  sporoblasts,  the  entire  process  taking  place  within 
the  nucleus  and  corresponding  to  the  so-called  "propagative  repro- 
duction" of  other  sporozoa.  The  spores  thus  formed  may  in  turn 
infect  fresh  nuclei  and  grow  directly  into  new,  secondary  sporoblasts 
which  give  rise  to  similar  spores,  a  true  "schizogeny"  and  a  second 
means  of  autoinfection  by  which  the  organism  spreads  throughout  the 
nuclei  and  cells  of  the  skin  and  possibly  to  many  of  the  other  organs 
of  the  body.  These  spores  may  finally  transmit  the  disease  to  new- 
hosts. 

Professor  Bosc,-  of  Montpellier,  France,  states  that  the  parasite  of 
variola  is  a  protozoon  which  presents  itself  in  two  forms — one  a  proto- 
plasmic and  the  other  an  intranuclear  form. 

The  bodies  described  agree  in  all  essential  features  with  those  por- 
trayed by  Councilman  and  his  associates. 

1  The  Life  Cycle  of  Cytoryctes  Variolas,  Guarnieri,  Journal  of  Medical  Research,  February,  1904. 
-  Ext.  des  comptes-reudus  des  seances  de  la  SociiSte  de  biologie,  October  17,  24, 1903,  etc. 


266  SMALLPOX 

In  vaccinia  Bosc  finds  parasites  which  are  intraprotoplasmic  and 
reproduce  by  direct  division.  Similar  bodies  were  repeatedly  found  in 
the  lesions  of  sheeppox.  In  the  latter  disease  Bosc  claims  to  find  changes 
in  the  lungs  and  liver  which  he  regards  as  carcinomatous.  Indeed, 
variola,  vaccinia,  sheeppox,  syphilis,  and  cancer  are  said  by  him  to 
contain  "parasitoid  intraprotoplasmic  bodies." 

Calkins  gives  the  following  provisional  classification  of  the  cytoryctes 
variolse  and  allied  sporozoa: 

Class.     Sporozoa. 

Subclass.     Myxosporidia. 

Subclass.     Neosporidia. 

Order.     Microsporidia. 

Tribe.     Polysporogenea. 

Family.  Cytoryctidae.  The  organism  forms  one  pansporoblast 
which  is  without  a  membrane.  Nuclei  absent.  (The  nosematidse  and 
phlistophoridffi  also  belong  to  this  tribe.) 

Genus.     Cytoryctes,  the  cause  of  variola. 

The  caryoryctes  (the  paramecium  parasite)  and  the  lymphosporidum 
(brook-trout  parasite)  also  belong  to  this  genus). 

Magrath  and  Brinckerhoff^  have  made  a  careful  microscopic  study 
of  nine  lesions  of  inoculated  smallpox  in  six  monkeys.  They  conclude 
that  certain  structures  identical  in  form  and  staining  reactions  with 
those  in  the  lesions  of  smallpox  in  man  are  found  within  the  epithelial 
cells  of  the  skin.  The  forms  develop  in  a  cycle  such  as  is  described  by 
Calkins.  The  developmental  series  corresponds  with  the  evolution  of 
the  lesion.  The  complexity  of  the  structure,  the  staining  reactions,  and 
the  serial  nature  of  the  bodies  preclude  the  possibility  of  their  being 
"products  of  degeneration." 

THE  DIAGNOSIS  OF  SMALLPOX. 

The  detection  of  smallpox  in  its  pustular  stage,  particularly  in  well- 
marked  eruptions,  is  a  facile  matter  even  for  the  merest  tyro  in  medicine. 
The  picture  of  a  profuse  pustular  variola  can  scarcely  be  mistaken 
for  anything  else. 

It  is  especially  the  mild  and  modified  forms  of  smallpox  that  present 
difficulties  in  diagnosis.  The  degree  of  protection  in  varioloid  may 
be  so  great  that  the  eruption  may  consist  of  but  a  few  papules,  or, 
indeed,  the  eruption  may  be  absent  altogether,  constituting  a  variola 
sine  exanthemate.  The  diagnosis  in  such  cases  would,  of  course,  present 
perplexities.  It  is  a  matter  of  considerable  importance  to  ascertain 
whether  variola  is  prevailing  in  a  community,  and  whether  the  patient 
has  been  exposed  to  the  infection.  The  inability  to  obtain  satisfactory 
testimony  as  to  direct  exposure  should  not  be  allowed  to  influence  the 
diagnosis,  as  infection  may  take  place  in  the  most  subtle  manner  and 
from  unsuspected  sources. 

1  On  the  Occurrence  of  Cytoryctes  Varlolse,  Guamieri,  in  the  Skin  of  the  Monliey  Inoculated  with 
Variola  Virus,  Journal  of  Medical  Research,  February,  1904. 


77//';  nfAfJNOSIS  OF  SMALIJ'OX  267 

The  degree  to  which  the  patient  is  |)n)tect<;(l  by  viucinntioii  or  previous 
attack  of  smallpox  should  always  he  investigated.  'J'lie  presence  of  a 
comparatively  recent  vaccine  scar,  or  f)its  of  a  former  attack,  would 
constitute  strong  presumptive  evidence  against  the  existence  of  smallpox 
in  the  individual. 

As  variola  is  communicable  during  the  initial  stage,  an  early  diagnosis 
often  becomes  liighly  important.  Tf,  in  a  given  case,  it  \h\  found  that 
the  patient  was  seized  witii  a  cliill  or  had  re})eated  rigors,  followed  by 
a  sudden  rise  of  temperature  to  an  unusually  high  degree,  and  that 
there  is  epigastric  tenderness,  irritability  of  the  stomach,  and  severe 
pain  in  the  lumbar  region,  variola  should  be  strongly  suspected.  If, 
together  with  these  symptoms,  there  can  be  obtained  a  history  of  expo- 
sure to  the  variolous  infection,  the  diagnosis  becomes  comparatively 
easy.  But  in  many  cases  of  variola,  and  particularly  of  varioloid,  the 
initial  symptoms  are  so  indefinite  that  a  diagnosis  is  quite  impo.ssible 
until  the  characteristic  eruption  appears. 

There  is  no  one  symptom  of  smallpox  which  is  so  characteristic  that 
it  may  not  be  absent.  Curschmann  regards  the  hemorrhagic  initial 
exanthem,  situated  principally  in  the  triangles  of  the  thighs,  as  pathog- 
nomonic, but  this  occurs  in  a  very  small  percentage  of  cases.  In  making 
a  diagnosis,  the  prevalence  of  an  epidemic,  the  vaccine  condition  of  the 
patient,  the  history  of  the  disease,  and  the  symptoms  as  they  present 
themselves  should  all  be  carefully  considered. 

The  initial  illness  of  smallpox  may  be  confounded  with  influenza, 
typhus  or  typhoid  fever,  meningitis,  and  acute  gastritis. 

La  Grippe. — In  severe  cases  of  la  grippe  the  disease  may  be  ushered 
in  with  intense  headache,  fever,  delirium,  and  violent  pain  in  the  back 
and  limbs,  symptoms  which  strongly  suggest  smallpox.  The  differential 
diagnosis  between  these  affections  would  be  impossible'  before  the 
appearance  of  the  eruption.  Knowledge  of  the  prevalence  of  the  one 
or  the  other  disease  would  be  an  aid  in  the  diagnosis. 

Typhus  Fever. — The  early  symptoms  of  typhus  fever  may  be  quite 
indistinguishable  from  those  of  the  initial  stage  of  smallpox.  The 
appearance  of  the  eruption  will  usually  establish  the  diagnosis.  The 
eruption  of  typhus  is  at  first  macular,  and  is  seldom  present  on  the  face; 
while  that  of  the  smallpox  is  papular,  and  begins  usually  upon  the 
forehead. 

Meningitis. — In  both  meningitis  and  variola,  violent  headache, 
delirium,  and  coma  may  develop.  In  the  cerebrospinal  form,  purpuric 
symptoms  are  not  uncommon,  but  retraction  of  the  head  and  rigidity 
of  the  muscles  of  the  neck,  so  commonly  seen  in  this  affection,  are 
seldom  encountered  in  smallpox. 

Typhoid  Fever. — It  is  surprising  how  many  patients  sent  into  the 
Philadelphia  Municipal  Hospital  with  smallpox  have  been  treated, 
during  the  initial  stage  of  the  disease,  as  cases  of  typhoid  fever.  This 
is  perhaps  owing  to  the  frequency  of  the  latter  disease  in  this  city.  In 
an  ordinary  case  of  enteric  fever  the  insidious  onset  and  the  gradual 
rise  of  temperature  will  distinguish  it  from  variola,  in  which  the  onset 


268  SMALLPOX     •] 

is  sudden  with  chilly  sensations,  fever  often  reaching  104°  or  105°  F., 
and  commonly  with  severe  headache,  backache,  and  vomiting. 

Acute  Gastritis. — ^The  error  of  confounding  the  early  manifestations 
of  variola  with  acute  gastritis  is  at  times  made  in  cases  in  which  the 
initial  illness  is  characterized  by  severe  and  persistent  vomiting,  with 
pain  in  the  pit  of  the  stomach.  Attention  to  the  associated  symptoms 
and  the  history  of  the  case  should  enable  one  to  arrive  at  a  correct 
diagnosis. 

The  mistaking  of  the  early  lumbar  pain  for  lumbago  could  only  result 
from  an  insufficient  examination  of  the  patient.  Lumbago  is  not 
attended  with  fever  and  the  other  constitutional  disturbances  that 
characterize  the  initial  illness  of  smallpox. 

Measles. — Measles  may  be  confounded  both  with  the  morbilliform 
prodromal  rash  and  with  the  beginning  true  eruption  of  variola.  The 
prodromal  rash  is  non-elevated,  irregular  in  distribution,  with  pre- 
dilection for  the  trunk  and  extremities,  of  evanescent  duration  (twenty- 
four  to  forty-eight  hours),  and  usually  appears  upon  the  second  day  of 
the  initial  illness  in  those  about  to  develop  the  eruption  of  varioloid. 
In  measles  catarrhal  symptoms  are  present  and  the  eruption  is  later  in 
making  its  appearance. 

That  measles  may  bear  a  close  resemblance  to  smallpox  is  evidenced 
by  the  fact  that  in  epidemics  of  variola  cases  of  measles  are  not  infre- 
quently sent  to  the  smallpox  hospitals  under  erroneous  diagnosis.  It 
is  the  confluent  form  of  variola  which,  in  the  early  eruptive  stage, 
resembles  measles  most,  for  in  this  type  of  the  disease  the  face  is  often 
considerably  suffused.  Standing  at  the  foot  of  the  patient's  bed  in 
such  cases  it  is  frequently  impossible,  from  the  appearance  of  the 
eruption  on  the  face  alone,  to  distinguish  between  the  two  diseases. 
Some  cases  of  measles  are  accompanied  by  more  papulation  than 
others,  particularly  on  the  face  and  wrists,  and  these  are  the  cases  that 
most  strikingly  simulate  smallpox. 

The  diagnosis  can,  in  the  vast  majority  of  cases,  be  determined  by 
attention  to  the  following  points: 

The  constitutional  symptoms  preceding  the  eruption  in  smallpox  are 
usually  more  severe  (temperature  104°  to  105°  F.)  and  are  commonly, 
though  not  always,  accompanied  by  pronounced  backache.  The 
temperature,  moreover,  falls  a  few  days  after  the  appearance  of  the 
eruption,  while  the  fever  in  measles  at  this  time  continues  high.  The 
catarrhal  symptoms  affecting  the  eyes  and  the  respiratory  passages 
and  the  buccal  eruption,  which  are  so  constant  in  measles,  are  absent 
in  smallpox,  at  least  during  the  prodromal  stage.  Close  inspection  of 
the  mouth  in  smallpox  may  reveal  the  presence  upon  the  soft  palate 
of  rounded,  glistening,  pinhead-sized,  reddish  elevations,  but  these 
differ  considerably  from  the  bluish  spots  on  the  buccal  mucous  mem- 
brane in  measles.  The  eruption  in  measles  consists  of  large  maculo- 
papules  which  are  soft  and  velvety  to  the  touch,  while  the  papules  of 
smallpox  are  smaller  and  have  a  firm  and  shotty  feel.  The  sweep  of 
an  experienced  hand  over  the  skin  will  often  suffice  to  differentiate  the 


Till']  I)fAaNf)SfS  OF  SMMJJ'OX  269 

two  diseases.  Where  there  is  dotibt,  twenty-four  liours'  deliiy  will 
dispel  all  uncertainty,  for  by  this  time  tlie  eni[)ti(ni  of  ni(;aslcs  will  have 
j)econie  flatter  and  more  diffuse,  and  the  pjipules  of  snuillpox  firmer 
and  nioi'c  distinctly  elevated. 

Scarlet  Fever.- -The  ])ccnli;ir  distribution  ;ind  flcc(in^r  fh;ir;if(cr  of 
the  scarlatiniform  j)i'odromal  rash  will  enable  one  to  distin^misli  it  froin 
scarlet  fever. 

Scarlet  fever  may,  however,  l)e  closely  siniulater]  by  that  form  f)f 
hem()rrhafj;ic  sniall])ox  in  which  the  entire  cutaneous  surface  becomes  the 
seat  of  a  diffuse,  dusky-red  rasfi,  especially  well  marked  in  the  crural 
triangle.  This  form  of  purpura  variolosa  is,  however,  usually  preceded 
l)y  excruciating  backache.  If  the  patient  be  watcherl  for  a  short  time 
a  few  ill-defined  vesicles  will  usually  make  their  appearance.  The 
development  of  hemorrhages  would  not  in  itself  })e  conclusive,  as  the.se 
might  occur  in  hemorrhagic  scarlet  fever,  except  that  hemorrhage 
beneath  the  conjunctiva  would  rather  indicate  the  existence  of  smallpox. 
The  early  occurrence  of  sore  throat  would  point  toward  the  scarlatinal 
nature  of  the  disease. 

Chickenpox. — Smallpox  may  be  distinguished  from  chickenpox,  the 
disease  with  which  it  is  most  often  confounded,  by  attention  to  the 
following  considerations : 

1.  Initial  Symptoms. — Fever,  headache,  backache,  chills,  vertigo, 
nausea,  vomiting,  etc.,  precede  by  two  or  three  days  the  outbreak  of 
the  variolous  eruption.  In  exceptionally  mild  cases,  however,  these 
symptoms  may  be  slight  or  absent.  In  chickenpox  there  is  usually 
complete  absence  of  illness  preceding  the  eruption.  In  some  cases, 
however,  particularly  in  adults,  we  have  occasionally  noted  a  prodromal 
illness  suggestive  of  but  much  milder  than  that  observed  in  smallpox. 
In  chickenpox  the  fever  and  the  eruption  usually  appear  simultaneously. 

2.  General  Symptoms. — The  constitutional  symptoms  are  usually 
more  severe  in  smallpox  than  in  varicella,  but  it  must  be  remembered 
that  we  may  encounter  mild  cases  of  smallpox  and  severe  cases  of 
chickenpox. 

3.  Distribution  of  Eruption. — In  smallpox  the  eruption  involves  with 
predilection  the  face,  hands,  and  feet;  upon  the  trunk  the  lesions  are, 
as  a  rule,  more  sparse.  In  chickenpox,  the  eruption  is  almost  invariably 
most  profuse  upon  the  trunk,  more  particularly  upon  the  back.  Small- 
pox prefers  the  exposed  surfaces  and  chickenpox  the  covered. 

It  has  been  stated  that  chickenpox  does  not  attack  the  palmar  and 
plantar  surfaces;  this  statement  is  fallacious,  inasmuch  as  the  palms 
and  soles  are  every  now  and  then  attacked  in  well-marked  cases.  Of 
course,  one  never  sees  such  a  profusion  of  lesions  on  these  surfaces  as 
is  seen  in  smallpox. 

4.  Character  of  the  Lesions .^ — In  smallpox  the  eruption  begins  as 
firm,  "shotty"  papules,  which  slowly  increase  in  size  and  develop  into 
vesicles  and  pustules.  The  vesicles  are  hard,  moderately  uniform  in 
size,  and  often,  althouo:h  not  invariablv,  show  umbilication;  thev  are 
multilocular  and  difficult  to  rupture  with  the  finger-nail.     Chickenpox 


270  SMALLPOX 

lesions  begin  as  vesicles  containing  perfectly  clear  serum;  they  have  a 
rather  soft  or  velvety  feel,  are  often  unilocular,  thin  roofed,  can  be  easily 
ruptured  with  the  finger-nail,  and  vary  greatly  in  size,  some  being  as 
small  as  a  millet  seed  and  others  as  large  or  larger  than  a  dime.  They 
do  not  umbilicate,  save  by  desiccation  beginning  on  their  centre.  The 
early  drying  with  the  production  of  a  depressed,  blackish  crust  in  the 
centre  and  irregular  puckering  of  the  pustule  on  the  periphery  is  highly 
characteristic  of  chickenpox. 

5.  Manner  of  Eruption. — ^The  smallpox  eruption  usually  comes  out 
in  a  single  crop  and  the  lesions  remain  quite  uniform  in  character.  (It 
should  be  remarked,  however,  that  the  eruption  on  the  face  is  always 
a  little  in  advance  of  the  development  elsewhere.)  The  chickenpox 
eruption  comes  out  in  crops  on  successive  or  alternate  days,  and  the 
lesions  may  be  seen  in  varying  stages  of  development.  The  coexistence 
of  recent  tense  vesicles,  older  puckered  vesicopustules,  and  dried  scabs 
is  highly  characteristic  of  varicella. 

6.  Course  of  Eruption. — Smallpox  lesions  undergo  a  gradual  evolution 
from  papule  to  crust  in  the  course  of  ten  to  twelve  days  (in  mild  cases 
five  to  six  days).  Chickenpox  lesions  last  from  two  to  four  days  (rarely 
longer)  and  then  crust.  The  severity  of  the  eruption  is  no  absolute 
guide  in  the  differential  diagnosis,  as  severe  cases  of  varicella  may  look 
far  more  formidable  than  mild  cases  of  smallpox.  The  crusts  of  small- 
pox are  dense  and  compact,  while  those  of  chickenpox  are  thin  and 
friable. 

While  each  group  of  symptoms  just  enumerated  is  characteristic 
respectively  of  smallpox  and  chickenpox,  and  while  there  should  be 
no  difficulty  in  differentiating  between  the  two  diseases  when  either 
group  is  complete,  yet  it  must  be  admitted  that  smallpox  sometimes 
occurs  in  a  form  so  atypical  as  to  make  it  difficult  to  decide  to  which 
category  the  symptoms  belong. 

It  may,  however,  be  stated  in  a  general  way  that  a  mildly  febrile 
eruption  appearing  without  prodromal  symptoms,  being  distinctly 
vesicular  from  the  beginning,  and  commencing  to  desiccate  on  the 
second  or  third  day,  should  be  regarded  as  chickenpox;  and,  on  the 
other  hand,  an  acute  exanthem  preceded  by  an  initial  stage  of  forty- 
eight  hours,  in  which  the  temperature  was  distinctly  elevated,  beginning 
as  papules  and  ending  in  vesicles  or  vesicopustules,  even  though  the 
period  of  evolution  be  short,  should  be  regarded  as  smallpox.  At  any 
rate,  it  would  be  advisable,  for  the  safety  of  the  public,  to  regard  such  a 
case  as  suspicious,  and  surround  it  with  such  precautionary  measures 
as  are  best  calculated  to  prevent  the  spread  of  infection. 

Syphilis. — It  may  at  first  seem  strange  that  syphilis  and  smallpox 
should  ever  be  confounded.  Upon  reflection,  however,  it  will  be  seen 
that  the  two  diseases  have  many  phenomena  in  common.  They  are 
both  infectious  diseases  due,  we  may  assume,  to  the  invasion  of  the 
blood  with  a  micro-organism.  Each  has  a  period  of  incubation  at  the 
end  of  which  there  develop  certain  general  manifestations  accompanied 
by  an  exanthem  and  an  enanthem.     The  resemblance  may  -be  still 


TIII<:  DIACINOSIH  OF  ^ MA  [J. POX  271 

furllier  acconiiuiled  by  tlie  fact,  that  the  viiriolafonn  .sy[)liiliflr'  is  rif^t 
rarely  associated  with  and  even  jjrecedcd  by  f(!ver  and  general  aches 
and  pains. 

It  is  pjirticnl.'irly  the  pustular  sypliiloderrn  whicli  is  apt  to  he  cf>n- 
founded  with  smallpox.  The  eruption  at  times  may  appear  rather  sud- 
deidy  and  j)ass  throufijh  the  stages  of  papule,  vesicle,  and  pustule  in  a 
surprisingly  brief  period  of  time.  The  lesions  may  be  quite  firm  to 
the  touch  and  in  other  respects  closely  simulate  those  seen  in  smallpox. 

In  syphilis  one  can  fre(|uently  obtain  (1)  a  hittory  of  injcrtion  and  a 
description  of  the  initial  lesion.  Indeed,  the  chancre  or  its  remains 
may  still  be  detected.  Not  uncommonly  there  are  present  associatfjd 
evidences  of  syphilis,  such  as  mucous  patches,  flat  condylomata,  ulcer- 
ation of  the  tonsils,  alopecia,  glandular  enlargement,  etc.  The  variola- 
form  syphilide  may  develop  after  the  disappearance  of  one  of  the 
earlier  syphilitic  eruptions. 

2.  The  onset  of  the  two  diseases  is,  as  a  rule,  quite  different.  The 
syphilitic  subject  will  usually  give  a  history  of  having  felt  weak  and 
debilitated  for  some  weeks.  If  fever  precedes  the  eruption  it  is  ordinarily 
not  very  high  and  is  not  accompanied  by  severe  prostration.  When 
the  eruption  appears  the  patient  usually  calls  upon  the  physician  at  his 
office  or  at  the  hospital.  We  do  not  note  that  sudden  illness  which 
precedes  unmodified  smallpox.  In  the  latter  disease,  two  or  three  days 
before  the  efflorescence  appears,  the  patient  experiences  a  chill  followed 
by  a  rise  of  temperature,  often  to  103°,  104°,  or  105°  F.  There  are 
severe  headache,  backache,  vomiting  or  nausea,  vertigo,  general  pains, 
and  severe  prostration.  The  patient,  instead  of  calling  upon  the 
physician,  sends  for  him. 

It  must  be  remembered,  however,  that  in  varioloid  the  initial  symp- 
toms may  be  mild  or  absent.  On  the  other  hand,  in  rare  cases,  syphilis 
may  present  an  initial  illness  which  strongly  counterfeits  that  of 
smallpox. 

3.  The  development  of  the  eruption  in  smallpox  is  rather  sudden. 
Ordinarily  in  twenty-four  to  forty-eight  hours  the  full  complement  of 
lesions  has  appeared.  In  syphilis  the  eruption  may  continue  to  come 
out  for  quite  a  number  of  days  in  successive  crops.  It  must  be  admitted, 
however,  that  in  modified  smallpox  three  or  four  days  may  sometimes 
elapse  before  the  complete  appearance  of  the  exanthera. 

4.  The  distribution  of  the  variolaform  syphilide  may  be  identical  with 
that  observed  in  smallpox.  Frequently,  however,  variations  may  be 
noted.  The  pustular  syphilide  may  involve  the  trunk  more  copiously 
than  the  face;  this  would  be  exceedingly  rare  in  well-marked  smallpox. 
The  dorsal  surface  of  the  wrists  and  hands  are  nearly  always  involved 
in  smallpox,  but  may  escape  entirely  in  syphilis.  The  palms  of  the 
hands  and  soles  of  the  feet  are  always  involved  in  severe  smallpox; 
in  moderate  eruptions  they  nearly  always  present  some  lesions,  and  in 
varioloid  they  may  or  may  not  escape  completely.  The  pustular  syphilide, 
on  the  contrary,  attacks  the  palmar  and  plantar  surfaces  with  the 
greatest  rarity.    The  writers  have  observed  in  one  case  a  single  lesion 


272  SMALLPOX 

upon  the  palm  of    one  hand,  and  in  another  instance  a  deep-seated 
pustule  upon  the  lateral  surface  of  the  sole. 

5.  The  character  of  the  eruption  in  syphilis  and  smallpox  may,  in 
the  beginning,  be  so  nearly  identical  as  to  make  a  diagnosis  from 
the  eruption  alone  quite  impossible.  It  will  be  noted,  however,  that  the 
efflorescence  of  smallpox  presents  a  much  greater  uniformity  in  the 
character  and  development  of  the  lesions  over  the  body  than  does 
syphilis.  Syphilis  is  characterized  by  an  essentially  multiform  erup- 
tion; it  is  not  uncommon  to  find  small  pustules,  large  pustules,  and 
papules  interspersed,  and  these  in  varying  stages  of  evolution  and  invo- 
lution. 

The  vesicles  and  pustules  of  syphilis  are  usually  conical  and  involve 
merely  the  summits  of  the  elevations;  they  never  become  full  and 
globular,  and  fill  the  entire  lesion  as  do  those  of  smallpox.  Beneath 
the  syphilitic  crusts  considerable  ulceration  not  uncommonly  occurs; 
according  as  this  is  slight  or  severe  there  will  be  seen,  upon  detachment 
of  the  crusts,  a  small,  reddish-brown  pigmented  stain  or  an  excavated 
ulcer.    The  latter  heals  with  the  production  of  a  depressed  scar. 

6.  The  course  of  the  syphilitic  eruption  is  relatively  chronic  compared 
with  that  of  smallpox.  The  lesions  of  variola  undergo  a  striking  change 
in  a  few  days.  The  syphilitic  efflorescence  is  indolent,  and  presents,  as 
a  rule,  no  decided  alteration  of  appearance  within  this  period  of  time. 
By  the  sixth  or  seventh  day  in  smallpox  the  lesions  develop  into  those 
large,  full,  round,  hemispherical  pustules  which  are  so  characteristic  of 
the  disease. 

Finally,  to  the  physician  who  has  seen  much  of  smallpox,  there  is  a 
something  in  the  picture,  an  impression  given  by  the  ensemble,  which, 
while  not  definable  in  language,  is,  nevertheless,  of  subtle  aid  in  the 
diagnosis. 

Roseola  Vaccinosa. — Vaccination  with  animal  virus  sometimes  causes 
an  erythematous  or  rubeoloid  rash,  known  as  roseola  vaccinosa,  to 
appear  from  the  eighth  to  the  twelfth  day  of  the  vaccine  disease.  We 
have  occasionally  known  this  rash  to  have  been  mistaken  for  the 
eruption  of  variola,  especially  during  epidemic  visitations  of  the  disease. 
The  distinguishing  features  are  that  it  accompanies  vaccinia,  that  it  is 
not  preceded  by  a  very  high  temperature,  and  that  it  consists  of  macules 
rather  than  papules. 

Acne. — Mild  cases  of  varioloid  exhibiting  but  a  few  papulopustules 
about  the  face  may  bear  a  close  resemblance  to  acne.  The  history  of 
exposure,  the  existence  of  an  initial  stage,  and  the  progressive  evolution 
of  the  lesions  will  speak  for  the  variolous  nature  of  the  eruption,  while 
the  presence  of  blackheads,  a  history  of  previous  outbreaks  in  the 
individual,  and  the  absence  of  preceding  illness  will  decide  in  favor  of 
acne. 

Drug  Eruptions. — Drug  eruptions,  particularly  those  resulting  from 
the  ingestion  of  the  iodides  and  bromides,  may  simulate  the  exanthem 
of  smallpox.  The  history  and  absence  of  an  invasive  stage  will  usually 
suffice  to  make  the  diagnosis  clear. 


77//';  I'lKXlNOhllH,  OF  SMALIJ'OX  275 

variola,.     C'ontrariwise,   in    (lie  ah,sciif;o  of  an   cpidfinic   miM   fasf.s  of 
,sinall|)ox  are  very  likely  to  be  overlooked. 

Whenever  the  diagnosis  between  smallpox  and  a  disease  simulating 
it  is  in  doubt,  observation  of  the  progress  of  the  eru[>tion  for  a  perifKl 
of  twenty-four  to  thirty-six  hours  will  tisnally  make  elear  the  nature 
of  the  disease. 

THE  PROGNOSIS  OF  SMALLPOX. 

Since  tlie  introduction  of  vaccination  the  presence  or  absence  of  a 
typical  vaccine  scar  on  a  })atient  is  an  important  factor  in  the  question 
of  prognosis  in  smallpox.  Formerly,  smallpox  was  not  only  more 
common,  but  uniformly  far  more  fatal,  and  therefore  nnich  more 
dreaded  than  at  the  present  time. 

During  the  last  century  but  few  diseases  claimed  a  greater  number 
of  victims  than  variola,  but  at  the  present  time,  especially  in  countries 
where  vaccination  is  carefully  and  systematically  practised,  the  pro- 
portion of  deaths  from  this  malady  is  not  greater  than  0.7  per  cent,  of 
the  entire  mortality,  and  where  revaccination  at  the  proper  age  is  also 
enforced,  this  proportion  is  even  much  less.  In  the  prevaccination 
period  one-tenth  of  all  the  children  born  died  from  smallpox;  now  the 
mortality  from  that  disease  among  young  children  where  vaccination  is 
compulsory  is  almost  nil.  According  to  Juncker  smallpox  killed  in  the 
prevaccination  days  on  an  average  400,000  persons  every  year  in 
Europe.  In  1803  King  Frederick  William  III.,  of  Prussia,  stated  that 
the  average  yearly  mortality  rate  from  smallpox  in  Prussia  was  40,000. 
In  Prussia,  where  vaccination  and  revaccination  are  rigidly  enforced 
at  the  present  day,  smallpox  is  almost  unknown. 

Age. — The  age  of  the  patient  is  of  the  greatest  importance  in  con- 
sidering the  prognosis  of  smallpox.  It  is  comparatively  rare  for  an 
infant  under  one  year  of  age  to  survive  an  attack  of  unmodified  small- 
pox. So  also  at  the  other  extreme  of  life  the  death  rate  is  excessively 
high.  In  children  of  from  one  to  five  years  of  age  the  disease  is  also 
very  fatal,  but  among  those  of  from  five  to  fifteen  years  the  chances 
of  recovery  are  rather  better  than  in  adult  life. 

Smallpox  Patients  Treated  in  the  Municipal  Hospital,  showing 
MoETALiTY  According  to  Age. 
series  i. 

Age.                                                       Cases.              Died.  Percentage. 

Under  1  year 60                      37  61.66 

1    to    15  years :-30                     187  35.28 

15    "    25     " 1362                      402  29.51 

25     "    45     " 1215                      365  30.04 

45  years  and  upward 227                       88  38.77 

Total 3394  1079  31.79 


276  SMALLPOX  '  ] 

SERIES   II. 

(Similar  table  with  somewhat  different  age  classification  ) 

Age.  Cases.  Died.  Percentage. 

Under  1  year 57  29  50.87 

1   to     5  years 159  50  31.45 

5    "     10     " 130  20  15.38 

10    "     15     " 66  8  12.12 

15    "     25     " 371  55  14.82 

25  years  and  upward 1096  172  15.69 

Total 1879  334  17.80 

The  above  tables  give  the  smallpox  mortality  according  to  age,  and 
include  both  the  vaccinated  and  the  unvaccinated  cases.  All  of  the 
patients  under  one  year  of  age  were  unvaccinated  except  a  few  who 
were  vaccinated  after  infection — i.  e.,  during  the  incubation  period. 
Likewise,  practically  all  of  the  children  under  five  years  of  age  were 
unvaccinated. 

In  Series  I.  are  included  the  statistics  of  the  large  and  malignant 
epidemic  of  1871-72,  and  of  a  subsequent  severe  epidemic;  while  in 
Series  II.  are  included  the  statistics  of  the  recent  and  much  milder 
epidemic  of  1901-02. 

Race. — When  smallpox  prevails  among  aboriginal  tribes  the  mortality 
is  extremely  high.  It  is  commonly  stated  that  the  death  rate  of  variola 
among  negroes  is  much  higher  than  among  whites.  This  statement 
has  scarcely  been  borne  out  by  our  experience.  Negroes  are  extremely 
negligent  as  regards  vaccination,  and  the  number  of  unvaccinated  blacks 
received  in  smallpox  hospitals  is  apt  to  relatively  exceed  the  number 
of  unvaccinated  whites.  A  truer  comparison  of  mortality  rates  will 
be  obtained,  therefore,  in  contrasting  the  unvaccinated  of  both  races. 

In  the  tables  here  shown,  the  mortality  rate  among  the  negroes  is 
somewhat  higher  than  among  the  whites,  although  the  difference  is 
not  great: 

Negroes  and  Whites  Admitted  to  Municipal  Hospital. 

Cases.  Deaths.  Percentage. 

White 6131  1530  24.95 

Black 1073  407  30.79 

Total        ....    7204  1937  2689 

Unvaccinated  Negroes  and  Whites. 

Cases.  Deaths.  Percentage. 

White 2036  910  44.69 

Black 637  315  49.45 

Total        ....     2673  1225  45.83 

Sex. — Sex  influences  prognosis  to  little  or  no  extent. 

Among  women  the  mortality  is  somewhat  increased  on  account  of 
their  liability  to  suffer  from  metrorrhagia,  or,  when  pregnant,  from 
miscarriage  or  premature  delivery.  The  occurrence  of  either  of  these 
accidents  or  the  presence  of  the  parturient  state  strongly  predisposes 
the  patient  to  the  hemorrhagic  form  of  the  disease.     The  mortality 


77//';  rnoaNosrs  of  sma  LLpr)X  277 

in  men  is,  on  the  other  hand,  considerably  increased  by  intemperance. 
Drunkards  or  constant  imbibers  seem  particularly  prf»nc  to  suffer 
Itoiu  licmorriiiif^ic;  sniall])OX.  We  have  found  jdrnost  all  forms  of  the 
disease  more  severe  amonff  bartenders,  "^'lie  powers  of  resisfanrc 
against  the  exhausting  influence  of  variola  are  often  so  diminished 
by  chronic  alcoholism  that  death  results  from  a  form  of  the  disease 
from  which  a  |)ati(Mit  with  more  healthy  organs  would  recover. 

Mania  a,  polil  constitutes,  of  course,  a  very  serious  foniplif.'ition.  In- 
temperate persons  are  apt  to  be  badly  nourislu-d,  .'ind  Ihis  conrliliou  is 
always  unfavorable  in  smallpox. 

It  will  be  seen  from  the  subjoined  Ijible  (iiiil  I  he  inorljility  rate  jimf»ng 
males  and  females  in  our  experience  has  been  almost  the  same: 

Cases  and  Mortality  According  to  Sex. 

Cases.  Deaths.  Percentage. 

Male 4593  1207  27.45 

Female 2606  670  25.71 

Total        ....     7204  1937  26.89 

Unmodified  smallpox  is  an  exceedingly  fatal  disease,  the  death  rate 
varying  in  different  epidemics  from  15  to  60  per  cent.  The  epidemic 
which  swept  over  this  and  other  countries  in  the  years  1S70  to  1872  was 
everywhere  characterized  by  unusual  malignancy,  and  the  mortality 
among  the  unvaccinated  cases  was,  in  some  places,  as  high  as  64  per 
cent.  The  following  table  shows  the  mortality  rate  among  vaccinated 
and  unvaccinated  cases  treated  in  the  Municipal  Hospital  during  the 
three  largest  epidemics  experienced  since  its  foundation: 

Mortality  Eate  of  Vaccinated  and  Unvaccinated  Cases  in 


Different 

Epidemics, 

Cases. 

Deaths. 

Percentage. 

1871-1872. 

Unvaccinated  . 

.      697 

449 

64.41 

Vaccinated 

.    1629 

276 

16  94 

Total       . 

.    2326 

725 

30.74 

1881-1885. 

Unvaccinated  . 

.      447 

252 

56.37 

Vaccinated       .       .       . 

.      551 

81 

14.70 

Total 

.      998 

333 

33.36 

1901-1904. 

Unvaccinated  . 

.    1943 

636 

32.73 

Vaccinated 

.    1844 

124 

6.72 

Total        ....    3787  760  20.06 

It  will  thus  be  seen  that  different  epidemics  vary  very  greatlv  in 
malignancy.  In  1901-04  the  mortality  rate  among  the  unvaccinated 
was  just  one-half  that  observed  in  1871-72,  and  almost  one-half  less 
than  the  death  rate  in  1881, 

Indeed,  smallpox  may  occur  in  epidemics  in  which  the  death  rate 
reaches  as  low  a  figure,  even  among  unvaccinated  cases,  as  2  per  cent. 
Such  a  remarkable  epidemic  has  been  prevailing  in  various  sections  of 
the  United  States  during  the  past  few  years. 

In  the  absence  of  an  epidemic  influence,  smallpox  is  usuallv  much 


278  SMALLPOX 

less  fatal.  It  is  believed  by  some  authors  that  the  disease  is  more  fatal 
at  the  beginning  and  during  the  maximum  of  an  epidemic  than  when 
it  is  declining,  but  we  are  not  sure  that  such  is  always  the  case.  Certain 
seasons  of  the  year  are  also  believed  to  exercise  some  influence  over 
the  mortality  from  the  disease.  It  is  probably  true  that  a  patient  is 
less  able  to  bear  the  depressing  effects  of  confluent  variola  when  the 
weather  is  excessively  hot  than  when  the  temperature  is  cooler. 

Type  of  Disease. — In  considering  the  prognosis  in  individual  cases 
various  circumstances  are  to  be  taken  into  account.  The  type  of  the 
disease  and  the  extent  and  depth  of  the  eruption  are  among  the  most 
important  factors.  The  hemorrhagic  form  of  smallpox  is  frightfully 
fatal.  Indeed,  it  may  be  laid  down  as  a  rule  almost  without  exception 
that  recovery  never  takes  place  from  the  graver  types  of  this  disease. 
Of  152  cases  of  hemorrhagic  smallpox  observed  during  the  epidemic 
of  1871-72,  146  died.  The  6  cases  that  recovered  belonged  to  the 
milder  variety  of  this  type;  1  had  slight  bloody  vomit,  and  the  other 
5  exhibited  an  eruption  which  on  some  parts  of  the  body  was  purplish, 
while  a  number  of  vesicles  contained  a  dark-blue  spot  in  the  centre, 
showing  that  blood  was  exuded  into  the  vesicles. 

The  next  most  fatal  form  of  smallpox  is  the  confluent  variety.  When 
it  is  comprehended  that  in  such  cases  there  may  be  forty  thousand  or 
more  pustules  present,  the  reason  for  the  high  death  rate  is  apparent. 
Of  211  cases  of  confluent  smallpox  accurately  observed  during  the 
epidemic  of  1871-72,  168  died,  showing  a  mortality  rate  of  79.62  per 
cent. 

Semiconfluent  cases  are  correspondingly  less  fatal  than  the  confluent; 
while  in  cases  with  discrete  eruptions  the  mortality  falls  to  a  compara- 
tively low  level. 

Thus  it  will  be  seen  that  the  prognosis  in  any  particular  case  is  influ- 
enced to  an  enormous  extent  by  the  character  of  the  eruption.  In 
varioloid  or  smallpox  so  modified  by  vaccination,  inoculation,  or  previous 
attack  that  the  secondary  fever  is  slight  or  absent,  the  mortality  is 
almost  nil,  as  will  be  seen  from  the  appended  table: 

Vakiola  and  Varioloid  Treated  in  the  Philadelphia  Municipal 

Hospital. 

Cases.  Deaths.  Percentage. 

Variola 4156  1906  45.93 

Varioloid 3048  31  101 

Total 7204  1937  26.89 

The  fatalities  in' varioloid  result,  as  a  rule,  from  some  complicating 
condition.  It  must  be  remembered  that  attacks  in  adult  patients  who 
were  vaccinated  in  infancy  and  showed  no  appreciable  protection  are 
classed  under  the  head  of  variola. 

The  stage  of  the  disease  at  which  death  occurs  in  smallpox  will 
depend  somewhat  upon  the  character  of  the  attack.  Patients  suffering 
from  hemorrhagic  variola  usually  succumb  on  the  fourth,  fifth  or  sixth 
day  of  the  eruption.  Considering  all  types  of  the  disease  the  largest 


77//';  f'U()(,'N()SlS  OF  SMALLPOX  270 

number  of  fatalities  occur  during  the  second  week  of  the  eruption  and 
particularly  upon  the  ninth,  tenth,  and  eleventh  days.  As  will  be  seen 
in  the  accompanying  table,  of  1019  fatal  cases  of  sn)all[)ox,  575,  or 
50.42  per  cent.,  died  during  the  second  week,  and  .'M7,  or  .':)4.05  percent,, 
of  these  exj)ired  on  the  ninth,  tenth,  and  eleventh  days.  Basing  the 
assertion  u[)()n  these  figures,  it  may  be  stated  that  over  one-third  of 
the  fatalities  occur  upon  the  critical  days  mentioned,  and  over  one-half 
of  the  deaths  during  the  second  week. 

We  have  occasionally  observed  death  to  take  place  as  late  as  five  or 
six  weeks  after  the  onset  of  the  disease,  but  in  these  cases  the  unfavorable 
termination  has  been  brought  about  by  some  complicating  affection. 

Showino  the  Period  of  the  Disease  at  which  1019  Cases  of  Smali.i-ox 

Proved  Fatal. 

First  week : 

Isl  day  of  ernptinn 1 

2d        ""           "  4 

3d         "           '•  14 

4th        "           " 31 

5th        "           "  63 

6th        "           "  90 

7th        "            "  90 

—  293 
Second  week : 

8th  day  of  eruption 84 

9th   "     "     122 

10th   "     "     114 

11th   "     "     101 

12th   "     " 75 

13th   "     "     .49 

14th   "     "     30 

—  575 
Third  week  : 

15th  day  of  eruption 28 

16th        "           "           22 

17th        "           "           12 

18th       "           "           9 

19th       "           "           5 

20th        "           "           8 

21st        "           "           7 

—  91 
Fourth  week  and  after: 

22d  day  of  eruption 7 

23d  "  "  . 8 

24th  "  "  6 

25th  "  "  3 

26th  "  "  4 

27th  "  " 3 

28th  "  "  5 

29th  "  "  4 

30th  "  " 4 

31st  "  " 2 

32d  "  "  4 

33d  "  "  1 

34th  "  " 2 

35th  "  "  1 

36th  "  "  S 

37th  "  "  I 

39th  "  "  1 

44tll  "  "  1          ' 

—  60 

Total 1019 


280  SMALLPOX 

Vaccinal  Condition. — ^The  vaccinal  condition  of  the  individual  is  a 
most  potent  factor  in  influencing  the  course  of  the  variolous  disease. 
The  degree  of  protection  conferred  by  the  vaccine  process  can  be,  in 
most  cases,  approximately  estimated  by  the  character  of  the  vaccine 
cicatrix.  Every  now  and  then  we  encounter  patients  with  good  vaccina- 
tion scars  from  an  infantile  vaccination,  in  whom  the  protection  against 
smallpox  has  been  almost  completely  lost;  and,  on  the  other  hand,  we 
may  see  patients  with  poor  scars  who  still  enjoy  considerable  protection; 
but  these  may  be  looked  upon  as  exceptions  to  the  general  rule. 

The  existence,  therefore,  of  good  cicatrices  in  a  patient  who  is  attacked 
with  smallpox  may  be  regarded  as  of  favorable  prognostic  import. 

Of  8893  cases  of  smallpox  treated  at  the  Municipal  Hospital,  2335 
presented  good  scars;  of  this  number,  152  died,  constituting  a  mortality 
rate  of  6.5  per  cent.;  1105  patients  with  fair  scars  were  treated,  of  whom 
135  died,  showing  a  death  rate  of  12.21  per  cent.;  1524  cases  were 
admitted  with  poor  scars,  of  whom  345  died,  giving  a  death  rate  of 
22.64  per  cent.;  3687  unvaccinated  cases  were  admitted,  of  whom 
1542  died,  giving  a  mortality  rate  of  41.82  per  cent.  Thus  it  is  seen 
that  the  danger  of  attacks  of  smallpox  can  be  measured  with  a  con- 
siderable degree  of  accuracy  by  the  vaccinal  condition  of  the  patient. 

Vaccinal  Condition  and  Mortality  Rate. 

Admitted.  Died.  Percentage. 

Vaccinated  in  infancy  (good  scars)      .        .    2335  152  6.5 

(fair        "  )       .        .    1105  135  12.21 

(poor      "   )       •        •     1524  345  22.64 

Postvaccinal  cases 4964  632  12.53 

Unvaccinated   " 3687  1542     ,  41.82 

Unclassified       " 242  45  18.18 

Total        ....     8892  2219  24.95 

There  is  no  reliable  symptom  during  the  initial  stage  to  indicate 
the  gravity  of  the  attack.  Not  infrequently  the  mildest  eruption  of 
varioloid  is  preceded  by  a  very  severe  febrile  stage.  If,  however,  the 
initial  stage  be  very  mild,  it  is  safe  to  prognosticate  a  moderate  eruption. 
Severe  lumbar  pains  may  be  present  both  in  modified  and  unmodified 
smallpox,  yet  if  they  be  extremely  severe  there  would  be  some  reason 
to  anticipate  a  hemorrhagic  form  of  the  disease.  Inasmuch  as  the 
initial  morbilliform  exanthem  {roseola  variolosa)  is  most  often  seen  in 
varioloid,  we  would  regard  the  presence  of  this  rash  as  an  indication 
that  the  true  eruption  will  be  of  modified  form.  When  the  rash  is 
of  the  scarlatiniform  type,  the  ensuing  eruption  may  be  moderate  or 
severe;  when,  however,  the  prodromal  rash  is  purpuric,  it  is  a  symptom 
of  evil  portent,  preceding  as  it  does  the  hemorrhagic  form  of  the  disease. 
There  are,  however,  exceptions  to  this  last  statement;  we  have  occa- 
sionally seen  erythematopurpuric  prodromal  rashes  in  persons  who 
have  made  perfectly  good  recoveries. 

It  has  been  already  stated  that  the  quantity  and  character  of  the 
eruption  are  accurate  guides  as  to  the  gravity  of  the  disease.     The 


riii<:  I'ttOGNOSis  of  sma/jj'hx  281 

condition  of  the  nnicous  membrane  of  the  [)[),'uynx,  hirynx,  and  traeliea 
should  he  regarded  as  only  second  in  in)j)(jrtance  to  the  skin  lesions  in 
estimating  the  degree  of  danger  in  variola.  If  these  parts  become 
severely  im])licated  by  the  variolons  f)rocess,  giving  rise  to  a  fliphtheritir 
condition  of  the  fances,  (lys[)hagia,  difhculty  of  res})iration,  or  ademji 
of  the  glottis,  the  case  shonld  be  viewed  with  grave  ap|)rehensif>ii. 
Even  hoarseness  at  the  early  period  of  the  rnaturative  stage  shonld  be 
looked  npon  with  suspicion. 

Favorable  Symptoms. — As  has  })een  stated,  mild  initial  manifesta- 
tions and  the  occurrence  of  a  roseolous  rash  are  favorable,  inasnnich 
as  they  precede,  as  a  rule,  mild  forms  of  the  disease.  Even  in  profuse 
eruptions,  if  the  pustules  become  prominent  and  acuminate  well,  and 
are  accompanied  by  considerable  swelling,  and  if  those  on  the  extremities 
are  surrounded  l)y  a  pinkish  areola,  and  the  patient  takes  nourishment 
freely,  there  is  good  ground  for  hope.  At  a  more  advanced  ])eri(Kl  of 
the  disease,  if  the  state  of  the  nervous  system  be  tranquil  and  the  patient 
passes  quiet  nights,  has  a  contented  disposition,  and  entertains  a  confi- 
dent hope  of  recovery,  the  probal)ility  of  a  favorable  termination  of 
the  disease  is  greatly  increased,  even  though  the  eruption  be  severely 
confluent. 

Unfavorable  Symptoms. ^ — Among  the  symptoms  which  indicate  the 
approach  of  a  hemorrhagic  attack  are:  excruciating  backache  during  the 
initial  stage,  a  petechial  prodromal  rash  in  the  axilla  and  groins,  sub- 
conjunctival ecchymoses  and  hemorrhages  from  the  various  mucous 
membranes,  a  claret-colored  areola  about  the  lesions  upon  the  extremi- 
ties, and  a  bluish  or  lead-colored  discoloration  of  the  centres  of  the 
vesicles.  The  prognosis  in  a  case  presenting  such  symptoms  would  be 
almost  hopeless. 

An  excessive  degree  of  confluence  on  all  parts  of  the  body  renders 
the  prognosis  extremely  grave.  It  is  an  unfavorable  sign  in  confluent 
cases  if  the  pustules  on  the  face  be  flat,  milky-white  in  color,  and  pasty, 
and  if  there  be  absence  of  sweUing.  It  is  also  ominous  to  see  here  and 
there  on  the  face  vesicles  desiccating  prematurely  and  producing  flat, 
brownish  scabs. 

During  the  early  period  of  maturation  the  patient's  condition  should 
be  regarded  as  extremely  critical  if  the  progress  of  the  eruption  be 
suddenly  arrested  and  the  swelling  of  the  face  and  hands  subside, 
leaving  the  skin  between  the  pustules  pale;  if  the  pustules  themselves 
shrink  and  collapse;  if  the  pulse  be  rapid,  dicrotic,  or  feeble;  if  the 
delirium  and  restlessness  increase;  or  if  nourishment  be  refused  or 
taken  very  reluctantly. 

Valuable  information  may  often  be  gained  by  observing  the  nervous 
symptoms,  especially  at  an  advanced  period  of  the  disease.  Great 
restlessness,  insomnia,  despondency,  constant  moaning  and  grindmg 
of  teeth  in  children,  are  unfavorable  symptoms.  Violent  and  protracted 
delirium,  convulsions,  or  coma  usually  preclude  all  hope  of  recovery. 

Even  after  the  patient  has  passed  safely  through  the  perils  of  the 
regular  stages  of  variola,  his  life  may  again  be  placed  in  jeopardy  by 


282  SMALLPOX 

certain  complications.  Fortunately,  those  which  are  most  frequent — 
furuncles  and  abscesses — rarely  lead  to  a  fatal  issue.  The  occurrence 
of  pneumonia,  pleuritis  with  effusion,  erysipelas,  or  abortion  should  be 
viewed  with  deep  concern.  But  the  most  fatal  of  the  complications 
liable  to  arise  are  suppuration  within  the  joints,  pyaemia,  and  empyema. 
Gangrene  of  the  scrotum  and  glossitis  variolosa  arising  earlier  in  the 
course  of  the  disease  usually  portend  a  fatal  outcome. 

THE  TREATMENT  OF  SMALLPOX. 

The  treatment  of  smallpox  may  be  considered  in  its  relationship, 
first,  to  the  patient  himself,  and,  second,  to  the  community  at  large. 
The  latter  aspect  of  the  subject  concerns  the  prophylaxis  or  preventive 
treatment  of  the  disease.  This  may  be  conveniently  classified  under 
the  following  captions — notification,  isolation,  surveillance  or  quarantine, 
disinfection,  and  vaccination. 

Prophylaxis.  Notification. — It  is  important  in  the  interests  of  public 
health  that  the  existence  of  a  case  of  smallpox  should  be  promptly 
made  known  to  the  proper  health  authorities.  It  is  usually  the  duty 
of  the  physician  in  attendance  to  transmit  this  intelligence.  Every 
practitioner  of  medicine  should  feel  himself  called  upon  to  aid  and 
sustain  the  sanitary  authorities  in  their  efforts  to  prevent  or  stamp 
out  a  pestilential  disease  and  should  willingly  comply  with  any  arrange- 
ments whose  object  is  the  attainment  of  so  desirable  an  end. 

Most  large  communities  have  enacted  laws  making  compulsory  the 
notification  of  smallpox  and  other  pestilential  diseases,  under  pain  of 
fine  or  imprisonment.  It  is  only  through  a  knowledge  of  the  distribution 
and  extent  of  smallpox  in  an  infected  district  that  the  health  authorities 
are  enabled  to  intelligently  and  efficiently  inaugurate  measures  toward 
its  suppression. 

Isoiation.^ — It  is  of  paramount  importance,  when  smallpox  appears 
in  a  community,  to  prevent  the  dissemination  of  infection;  to  this  end 
the  isolation  of  the  patient — the  source  of  the  infection — becomes 
essential.  This  can  only  be  accomplished  with  any  degree  of  certainty 
by  having  the  sick  removed  to  a  well -organized  hospital.  General 
hospitals  and  other  public  institutions  cannot,  with  justice  to  the  other 
patients  or  inmates,  harbor  and  treat  those  suffering  from  smallpox. 
Even  the  caring  for  such  patients  in  isolated  pavilions  in  general  hospitals 
is  open  to  the  objection  of  multiplying  the  foci  of  contagion  in  the 
city  or  town.  It  follows,  therefore,  that  every  city  and  large  town 
should  be  provided,  either  temporarily  or  permanently,  with  a  special 
institution  for  the  treatment  of  this  disease  in  the  event  of  its  outbreak. 
It  should  be  located  in  a  healthful  district,  sufficiently  removed  from 
the  thickly  settled  portions  of  the  city  to  preclude  the  possibility  of 
transmitting  the  contagion  to  inhabited  domiciles,  but  not  so  remote 
as  to  interfere  with  its  accessibility.  It  is  also  of  importance  that  such 
institutions  should  be  constructed  in  a  modern  manner,  with  a  view 
to  making  the  unfortunate  patients  as  comfortable  as  possible. 


TIII<:  TliNATMHNT  OF  >SMALLPOX  ^HP, 

Of  course,  a  special  hospital  of  this  character  should  he  rnanagefi 
under  strict  quariuitine  regulations.  No  person,  however  well  protef:ted, 
should  be  allowed  to  visit  a  patient  in  the  institution  (;xce[)t  under 
extreme  circumstances,  and  then  only  after  every  possible  precaution 
shall  have  been  taken  to  prevent  his  carrying  away  the  infection.  The 
nurses  and  attendants  should  not  be  allowed  to  leave  the  hospital,  nor 
come  in  contact  with  other  persons,  until  they  have  had  an  antiseptic 
bath  and  have  chanfrcd  their  infected  clothing.  In  j)roviding  nurses 
and  other  employ(5s  for  the  hospital  it  need  not  be  required  that  they 
shall  have  had  smallpox,  but  they  should  invariably  be  vaccinated  or 
revaccinated  before  entering  upon  duty.  When  delay  is  possible  it 
is  wise  to  await  the  result  of  such  vaccination  before  the  individual 
is  brought  into  the  infected  atmosphere.  The  hospital  should  be 
supplied  with  closed  ambulances  for  the  transportation  of  patients. 
Private  or  public  vehicles  should  never  be  used  for  this  purpose.  Indeed, 
this  is  regarded  as  so  important  a  matter  that  in  some  large  cities  in 
this  country  the  use  of  any  kind  of  public  conveyance  for  carrying 
persons  afflicted  with  smallpox  is  prohibited  by  law,  and  its  infringe- 
ment is  made  punishable  by  fine. 

Lest  infection  be  spread  by  the  ambulance  itself  it  should  be  dis- 
infected and  provided  with  clean  bedding,  blankets,  etc.,  every  time 
it  is  used.  In  order  that  the  public  may  know  the  character  of  the 
disease  that  it  conveys,  it  should  bear  the  name  of  the  hospital  to  which 
it  belongs. 

If  the  smallpox  patient  is  to  be  treated  at  home,  every  possible  effort 
should  be  made  to  seclude  him  from  all  persons,  excepting  only  such 
as  are  required  to  act  as  nurses,  and  they  should  be  protected  by  recent 
vaccination.  In  selecting  the  apartment  for  the  patient,  a  room  most 
completely  separated  from  all  other  parts  of  the  house  is  to  be  preferred. 
If  this  is  not  practicable — which  is  usually  the  case  in  the  ordinary  city 
residence — the  uppermost  room  of  the  house  should  be  preferred.  It 
should  be  well  ventilated,  and,  if  possible,  have  an  open  fireplace  in 
which  fire  should  be  kept  constantly  burning.  All  unnecessary  articles 
of  furniture,  such  as  drapery,  upholstery,  carpets,  etc.,  should  be 
removed.  Every  precaution  in  regard  to  cleanliness  and  disinfection  of 
bedding,  clothing,  and  everything  in  use  in  the  room  should  be  exercised, 
so  that  the  danger  of  spreading  the  infection  shall  be  reduced  to  the 
minimum,  A  sheet  wrung  out  in  a  strong  solution  of  carbolic  acid, 
Labarraque's  liquid,  or  some  other  disinfectant,  and  suspended  across 
the  doorway  may  aid  in  preventing  the  infection  from  being  disseminated 
to  other  parts  of  the  house.  The  spaces  around  doors  that  are  not  in 
use,  which  communicate  with  parts  of  the  house  to  be  protected,  should 
be  sealed  by  pasting  strips  of  wrapping  paper  over  them. 

Surveillance  or  Qaarantine. — When  smallpox  appears  in  a  house,  the 
question  arises.  What  shall  be  done  with  the  exposed  but  well  members 
of  the  household  ?  If  the  patient  is  treated  at  home,  the  other  inmates 
as  well  as  the  sufferer  should  be  quarantined.  For,  if  removed  to 
another  locality,  save  to  a  quarantine  station  or  hospital,  the  disease 


284  SMALLPOX  pn 

might  subsequently  appear  there,  and  a  new  centre  of  infection  be 
thus  estabhshed.  To  depend  upon  people  voluntarily  to  curtail  their 
personal  liberty  for  the  public  good  would  be  confiding  too  much,  at 
the  present  time,  in  human  benevolence  and  public  spirit.  Therefore, 
the  best  results  "will  be  obtained,  when  the  patient  is  retained  at  home, 
by  stationing  reliable  guards  about  the  house  to  enforce  detention 
of  the  exposed  inmates  and  also  all  other  necessary  precautionary 
measures. 

On  the  other  hand,  when  the  patient  is  removed  to  the  hospital  it 
is,  in  our  judgment,  not  necessary  to  enforce  the  above-mentioned  restric- 
tions. Indeed,  we  are  of  the  belief  that  the  object  desired  is  often 
defeated  in  large  cities  by  a  routine  quarantine  of  the  inmates  of  houses 
from  which  smallpox  patients  have  been  removed.  To  make  such 
a  quarantine  effective  the  individuals  should  be  detained  for  a  period 
of  eighteen  days,  the  outside  limits  of  the  stage  of  incubation.  Segrega- 
tion of  the  inmates  of  the  household  for  so  long  a  period  works  a  great 
personal  hardship  and  prompts  them,  in  many  instances,  to  escape 
before  the  quarantine  is  placed  upon  the  house.  We  have  known 
persons  frequently  to  flee  from  houses  where  there  existed  an  individual 
suspected  of  having  smallpox,  but  in  whom  the  diagnosis  had  not  been 
definitely  made.  The  settling  of  these  exposed  persons  in  different  parts 
of  the  same  city  and  in  other  cities  results  in  the  outbreak  of  the  disease 
in  these  various  localities.  Thus,  instead  of  limiting  the  infection  rigid 
quarantine  laws  may  favor  its  dissemination.  Furthermore,  unpopular 
restrictive  measures  tend  to  provoke  evasion  of  the  law  and  concealment 
of  the  existence  of  the  disease. 

When  the  patient  is  removed  to  the  hospital  we  would  advise  immediate 
vaccination  of  the  exposed  individuals.  To  avoid,  as  far  as  possible, 
failures  through  imperfect  virus  or  technique,  three  or  four  insertions 
with  different  virus  had  better  be  made.  At  the  same  time  there  should 
be  thorough  disinfection  of  the  infected  articles  and  apartments.  After 
this  has  been  accomplished  the  exposed  individuals  might  resume 
their  freedom.  They  should,  however,  be  kept  under  medical  surveil- 
lance, and  should  be  daily  visited  by  a  physician  who  should  watch  for 
any  symptoms  of  variola.  Such  inspection  should  be  continued  for 
sixteen  days  from  the  onset  of  the  disease  in  the  original  patient,  at  the 
end  of  which  time  the  suspected  individuals,  if  well,  may  be  exempted 
from  further  surveillance.  During  his  visits  the  physician  can  determine 
whether  the  vaccinations  are  "taking,"  and,  if  not,  the  procedure  can 
be  repeated,  thus  giving  the  patient  a  still  further  chance  of  protection 
if  vaccinal  susceptibility  exists. 

The  above  plan  is  based  upon  the  assumption  that  smallpox  is  not 
contagious  during  the  period  of  incubation,  and  this  view  is  in  accord 
with  the  belief  held  by  practically  all  authorities  on  the  subject.  Until 
active  symptoms  manifest  themselves  the  exposed  individual  is  not  a 
menace  to  the  health  of  the  community,  and  it  is  unnecessary  and 
injudicious  to  restrict  his  liberty  during  this  period.  Furthermore,  a 
large  experience  has  demonstrated  to  us  that  under  a  system  such  as 


TTIE  TREArM/'JNT  OF  SMALLPOX  285 

outlined,  a  much  larger  percentage  of  exposed  individuah  v:ill  submit 
to  vaccination  and  a  correfijxmdingly  increased  numljcr  of  patients  V)ill 
consent  to  he  rem,oved  to  the  hospital,  for  only  those  who  comply  with 
this  advice  will  be  exempted  from  quarantine. 

Apart  from  these  considerations,  the  system  of  routine  (|n;iniritirie, 
during  epidemic  prevalence  of  smallpox,  will  he  f(jnn(l  to  involve  the 
expenditure  of  laro;e  sums  of  money. 

The  quarantining  of  exposed  persons  may  be  practicable  and  wise 
in  dealing  with  sporadic  cases  of  smallpox  or  with  the  first  cases  in  a 
community,  for  under  such  circumstances  extraordinary  precautions 
are  justified  in  an  endeavor  to  limit  the  outbreak  of  the  disease  to  the 
original  patients. 

Another  means  of  restricting  the  spread  of  smallpox  is  to  apprise  the 
public  of  the  particular  locality  in  which  the  disease  exists,  so  that 
no  one  may  unknowingly  approach  within  infecting  distance  of  the 
place.  But  how  to  do  this  without  exciting  unnecessary  alarm  is  a 
problem  not  easy  of  solution.  The  plan  adopted  in  some  cities  of 
placarding  the  infected  house  with  a  large  and  conspicuous  poster  is 
believed  by  many  to  serve  a  useful  purpose,  notwithstanrling  the  fact 
that  it  frequently  meets  with  much  opposition.  But  whether  this  plan 
be  adopted  or  not,  the  sanitary  authorities  should  keep  the  premises 
under  constant  supervision,  instituting  daily  visits  by  officers  qualified 
and  empowered  to  advise  and  direct  the  observance  of  proper  sanitary 
precautions. 

Disinfection. — Disinfection  is  a  highly  important  prophylactic 
measure.  The  infection  of  smallpox  is  not  only  imparted  to  the  atmos- 
phere surrounding  the  patient,  but  to  all  articles  which  have  been 
used  by  him  or  have  been  near  him.  It  clings  to  these  articles  for  a 
variable  length  of  time,  and  they  are,  therefore,  not  infrequently  the 
media  by  which  the  infection  is  conveyed  to  others.  Disinfection 
consists  in  the  complete  destruction  of  the  infecting  agent  of  the  disease. 
Fresh  air  and  sunlight  are  nature's  disinfectants;  when  infected  articles 
are  freely  exposed  to  the  atmosphere  and  rays  of  the  sun  for  some  time 
the  infecting  principle  becomes  less  and  less  active,  and  finally  dis- 
appears. Therefore,  the  house,  especially  the  room,  occupied  by  the 
patient  should  be  freely  though  cautiously  ventilated.  If  the  weather 
be  cool,  an  open  fire  upon  the  hearth  would  consume  much  of  tlie 
infected  atmosphere. 

Chemical  substances,  however,  furnish  the  more  speedy  and  reliable 
disinfectants,  and  it  is  upon  such  that  we  mainly  depend  for  the  destruc- 
tion of  the  disease  germs.  Some  agent  of  this  nature  should  be  brought 
directly  in  contact  with  all  the  excrementitious  matter  from  the  patient, 
and  with  everything  that  has  been  used  by  him  or  has  been  near  him 
during  the  progress  of  the  disease.  All  discharges,  not  excepting  those 
from  the  mouth  and  nose,  should  be  received  into  a  vessel  containing 
some  such  disinfectant  as  chloride  of  lime,  carbolic  acid,  or  bichloride 
of  mercury.  Under  no  circumstances  should  the  excreta  be  allowed 
to  flow  into  the  sewer  or  be  cast  awav  without  first  l^a^•in£:  undergone 


286  SMALLPOX 

disinfection.  In  country  districts,  where  disinfectants  may  not  be 
readily  obtained,  the  discharges  should  be  deeply  buried  in  the  ground 
in  a  locality  where  there  is  no  danger  of  contaminating  the  water  supply. 
Every  handkerchief,  towel,  and  article  of  bedding  and  clothing  used 
by  the  patient  should  be  steeped  for  some  time  before  leaving  the  room 
in  a  solution  of  two  fluidounces  of  chloride  of  zinc  or  four  fluidounces 
of  carbolic  acid  to  the  gallon  of  water,  and  afterward  boiled  by  them- 
selves for  half  an  hour  or  longer  in  plain  water;  all  small  articles,  such 
as  bits  of  linen,  sponge,  absorbent  cotton,  and  the  like  should  be  burned 
immediately;  all  utensils  used  for  eating  and  drinking  should  be  purified 
by  boiling  water;  and,  in  short,  nothing  should  be  allowed  to  leave 
the  room  without  having  first  been  subjected  to  some  form  of  disin- 
fection. 

The  attendants  should  not  be  more  numerous  than  the  necessities 
of  the  case  require.  They  should  be  carefully  instructed  in  regard  to 
the  importance  of  cleanliness,  disinfection,  and  isolation.  Not  only 
should  they  be  instructed  to  exclude  from  the  sick-room  all  persons 
not  having  authority  to  enter,  but  also  all  domestic  animals,  such  as 
the  dog  and  cat,  as  they  are  exceedingly  liable  to  serve  as  conveyers 
of  the  infection. 

The  clothing  of  the  attendants  should  be  of  such  material  as  can  be 
readily  boiled  and  washed,  and  it  should  be  frequently  changed  and 
subjected  to  this  process.  No  attendant  while  engaged  with  the  case 
should  come  in  contact  with  other  persons.  On  leaving,  either  tempo- 
rarily or  permanently,  a  bath  should  first  be  taken,  using  freely  carbolic 
acid  soap,  and  the  hair  should  be  washed  with  a  solution  of  mercuric 
chloride.  No  clothing  that  has  at  any  time  been  in  the  infected  atmos- 
phere should  be  worn  or  carried  away  from  the  premises,  unless  it  has 
first  been  disinfected. 

Physicians  should  also  exercise  care  lest  they  may  be  the  means  of 
communicating  the  infection.  When  called  upon  to  attend  a  case  of 
smallpox  the  physician  should  not  remain  in  the  infected  atmosphere 
longer  than  is  necessary  to  make  a  proper  examination ;  the  prescription 
may  be  written  and  advice  given  in  another  apartment.  After  each 
visit  he  should  carefully  wash  his  hands,  face,  and  hair;  his  hands 
especially  should  be  washed  in  some  disinfecting  solution.  He  should 
then  expose  himself  for  a  considerable  time  in  the  open  air  before 
visiting  another  patient. 

The  physician  should  wear  in  the  sick-chamber  a  long  mackintosh 
or  a  linen  duster  buttoned  up  to  the  chin,  and  a  cap  to  cover  the  hair, 
and  these  garments  should  be  kept  hanging  in  the  open  air  in  the 
intervals  of  his  visits.  In  hospitals  where  there  are  many  patients  to 
be  examined,  and  where  he  is  required  to  spend  considerable  time  in 
the  wards,  nothing  short  of  a  change  of  his  entire  outer  clothing  before 
leaving  the  institution  should  be  considered.  It  is  also  of  importance 
for  the  physician  to  cover  his  shoes  with  rubbers,  so  that  no  variolous 
crusts  which  may  be  upon  the  floor  will  be  carried  out  of  the  infected 
house. 


THE  T  UK  AT  ME  NT  OF  SMAfJ/POX  287 

The  isolation  of  a  smallpox  patient  should  he  continued  until  all  the 
scabs  are  removed.  The  time  necessary  to  effect  their  separation  varies 
greatly  in  (h'fferent  cases.  In  severe  confluent  forms  of  the  flisease  a 
month  or  more  will  he  required,  while  in  extremely  mild  and  abortive 
cases  of  varioloid  the  skin  may  be  entirely  smooth  in  a  week  or  ten 
days.  Upon  the  palms  and  soles  the  inspissated  pocks  remain  embedded 
for  a  long  time  and  recjuire  mechanical  removal  in  order  to  avoid  a 
long  and  tedious  waiting  for  spontaneous  exfoliation.  Even  after 
removal  of  the  variolous  crusts  the  patient  shoidd  not  be  allowed  to 
associate  with  the  pubHc  until  he  has  had  one  or  more  antiseptic  baths. 
Perhaps  the  most  reliable  antiseptic  bath  that  can  be  given  is  one 
containing  corrosive  sublimate.  The  safest  way  one  may  proceed  in 
the  use  of  such  a  bath  is  by  simply  sponging  the  body  and  carefully 
wetting  the  hair  with  the  solution  (1:2000)  and  then  have  the  patient 
freely  bathed  in  plain  water  with  the  use  of  carbolic  acid  soap,  or  the 
patient  may  take  a  full  bath  in  a  tub  containing  a  1:10,000  or  1: 
20,000  solution  of  mercuric  chloride.  A  5  per  cent,  solution  of  Labar- 
raque's  hquid  also  makes  a  very  reliable  disinfecting  bath.  After  this 
he  should  put  on  clothing  which  has  not  been  exposed  to  the  infection, 
or,  if  exposed,  has  been  disinfected,  and  he  may  then  safely  mingle  with 
the  public. 

Inasmuch  as  the  body  of  a  person  who  has  died  of  smallpox  is  capable 
of  imparting  the  infection,  some  precautions  should  be  observed  in 
regard  to  it.  For  instance,  the  body  should  be  thoroughly  wet  with 
a  solution  of  corrosive  sublimate  (1 :  1000)  or  with  a  solution  of  chloride 
of  lime  in  proportion  of  six  ounces  of  the  drug  to  a  gallon  of  water,  or 
with  some  other  equally  powerful  disinfectant;  besides,  it  should  be 
wrapped  in  a  sheet  saturated  with  one  of  these  solutions  and  buried  at 
once.  The  preferable  method  of  disposing  of  the  dead  from  this  disease 
is  by  cremation;  but  this  method  is  yet  perhaps  too  strongly  opposed 
by  public  sentiment  to  be  practicable.  It  is  not  advisable  to  transport 
the  corpse  a  long  distance  or  from  one  city  to  another  for  burial,  but 
if  this  be  really  necessary,  it  should  first  be  placed  in  a  metallic  coffin 
hermetically  sealed.  In  its  burial  it  should  be  put  at  least  six  feet 
under  ground,  and  should  not  be  disinterred  unless  absolutely  necessary, 
and  then  only  under  sanitary  supervision.  The  vehicle  used  for  con- 
veying the  body  to  the  grave  should  afterw^ard  be  disinfected.  It  is, 
perhaps,  unnecessary  to  say  that  the  funeral  should  by  no  means  be 
public. 

After  the  sick  chamber  has  been  vacated,  either  by  recovery  or  death 
of  the  patient,  every  article  it  contains  of  no  great  value  should  be 
immediately  burned.  Everything  else  which  will  not  be  injured  by  the 
ordinary  operation  of  the  laundry  may  be  safely  and  cheaply  disinfected 
by  immersion  in  boiling  water  for  half  an  hour.  It  should  be  remem- 
bered, however,  that  the  water  must  be  maintained  at  the  boiling  point 
for  that  length  of  time.  But  if  it  is  impracticable  to  subject  such  articles 
at  once  to  the  boihng  process,  they  should  be  immersed  for  about  four 
hours  in  some  reHable  disinfecting  solution — such  as^mercuric  chloride 


288  SMALLPOX 

In  the  proportion  of  1 :  2000,  or  carbolic  acid  1 :  50 — and  subsequently 
boiled. 

The  sick-room  should  be  disinfected  according  to  the  principles  laid 
down  in  the  chapter  on  disinfection.  The  room  should  then  remain 
closed  from  twelve  to  twenty-four  hours,  afterward  opened,  thoroughly 
ventilated,  and  all  surfaces,  including  the  furniture,  washed  with  a 
disinfecting  solution  (chloride  of  lime,  carbolic  acid  1 :  50,  or  mercuric 
chloride  1 :  1000) ;  afterward  the  floor  and  other  woodwork  should  be 
thoroughly  scrubbed  with  soap  and  water.  The  wall-paper,  if  there 
be  any,  should  be  well  moistened  with  the  carbolic  acid  solution  and 
scraped  off  and  burned.  Paper  may  be  reapplied  or  the  walls  white- 
washed, according  to  fancy.  In  addition  to  all  these  precautions,  it  is 
advisable  to  have  the  room  remain  unoccupied  for  three  or  four  weeks, 
during  which  time  it  should  be  well  aired. 

For  disinfection  of  outer  clothing,  carpets,  bedding,  and  all  articles 
which  cannot  be  boiled,  there  is  nothing  superior  to  steam  under  pressure. 
The  germs  of  smallpox  will  certainly  perish  if  exposed  for  half  an  hour 
to  this  agent  at  a  temperature  of  230°  F.  There  are,  however,  certain 
articles  which  would  be  injured  by  moist  heat,  and  for  the  disinfection 
of  these  dry  heat  may  be  substituted.  In  this  case  a  temperature  of  at 
least  230°  F.,  continued  for  two  hours,  will  be  required.  Formal- 
dehyde, however,  could  be  used  instead  of  dry  heat. 

Vaccination. — Of  all  of  the  measures  employed  to  prevent  the  spread 
of  smallpox,  none  is  so  important  and  efficacious  as  Jenner's  great 
discovery.  There  is  perhaps  no  single  scientific  fact  better  established 
than  that  vaccination,  periodically  repeated,  is  capable  of  effectually 
preventing  the  occurrence  of  that  disease  in  man.  In  view  of  this  fact 
it  does  at  first  sight  seem  strange  that  variola  should  continue  to  prevail 
in  civilized  communities;  and,  while  nothing  appears  easier  than  to 
control  the  spread  of  this  disease,  or  even  to  eradicate  it  altogether, 
yet  there  are  diflaculties  in  the  way  of  accomplishing  this  end  which 
seem  almost  insurmountable.  These  arise  from  various  causes,  but 
chiefly  from  individual  carelessness  or  indifference  about  employing 
vaccination,  and  from  the  absence  of  a  general  law  making  it  compulsory. 
We  know  that  many  conscientious  citizens  are  opposed  to  enforcing 
vaccination  by  law,  but  as  every  unvaccinated  person  is  liable  to  contract 
smallpox  and  disseminate  the  infection  among  others,  he  should  be 
regarded  in  the  light  of  a  public  enemy,  and  dealt  with  accordingly. 
Surely  it  is  not  an  unreasonable  position  to  assume  that  no  person 
through  ignorance  or  prejudice  should  be  allowed  to  contravene  the 
public  welfare. 

But,  in  the  absence  of  a  statutory  law  requiring  the  vaccination  of  all 
persons,  very  much  can  be  done  in  the  way  of  enforcing  the  measure 
by  restricting  the  privileges  of  the  unvaccinated.  For  instance,  satis- 
factory evidence  of  successful  vaccination  should  be  required  of  every 
child  before  admission  into  public  and  private  schools  and  institutions 
for  the  care  of  children;  no  unvaccinated  person  should  be  allowed  to 
serve  as  a  soldier  in  the  army  or  navy,  or  in  the  State  militia;  and  no 


Tiii<:  tiii<:atmknt  of  smallpox  280 

unvacci Mated  iiinnin;ni,nl,  slioiild  ho  jillowcd  lo  hmd  until  \;ifciii;itif>M 
has  been  perfoniied. 

In  view,  therefore,  of  the  <,n-e;it  importance  of  lliis  prophylactic 
measure,  it  l)ecomes  the  (hity  of  all  nmiiicipal  and  Stjde  autliorities  to 
j)rovide  gratuitons  Viiccination  for  the  ])oor,  and,  in(h-ed,  ff)r  all  helpless 
children  of  careless  or  improvident  j)arents,  no  matter  to  what  class  of 
society  they  belong.  No  expenditure  of  money  should  be  spared  by 
these  authorities  in  order  to  protect  their  citizens  against  a  disease  so 
loathsome  and  fatal  as  smallpox.  From  a  purely  monetary  ])oint  of 
view  such  expenditure  is  wise,  for  a  single  epidemic  of  this  much  dreaded 
disease  in  a  community  may  necessitate  a  greater  outlay  to  care  for  the 
indigent  sick  alone  than  would  be  required  to  purchase  the  means  of 
protection  for  that  community  for  a  decade  of  years. 

If  vaccination  were  universally  practised,  and  repeated  from  time 
to  time  as  circumstances  recjuired,  there  would  be  little  need  for  other 
means  of  prevention.  Whenever  a  case  of  smallpox  occurs  in  a  family, 
the  physician's  first  duty  is  to  vaccinate  promptly  all  members  of  the 
family  who  have  never  been  vaccinated,  and  revaccinate  all  others 
without  regard  to  the  character  of  their  previous  vaccination.  It  is  a 
good  plan  to  vaccinate  on  several  successive  days  those  who  have  never 
been  previously  subjected  to  this  procedure,  in  order  to  increase  the 
probability  of  obtaining  a  successful  result.  If  this  be  done  and  the 
patient  sent  to  the  hospital,  the  disease  may  be  prevented  from  spreading. 

Care  of  Patient.^ — In  order  to  consider  in  detail  the  treatment  of 
smallpox  it  seems  most  convenient  to  divide  the  disease  into  its  various 
stages,  as  follows:  (1)  the  stage  of  incubation;  (2)  the  initial  stage; 
(3)  the  eruptive  stage;  (4)  the  stage  of  suppuration;  (5)  the  stage  of 
retrogression,  or  stadium  exsiccationis. 

1.  The  Stage  of  Incubation.- — The  interval  between  the  reception  of 
the  infecting  agent  of  smallpox  into  the  blood  and  the  earlier  manifesta- 
tions of  the  disease  is  usually  unattended  by  symptoms.  There  is  no 
doubt,  however,  that  certain  unknown  processes  take  place  during  this 
period.  It  is  very  important  to  know  whether  an^ihing  can  be  done 
at  this  time  to  arrest  or  change  these  processes  so  as  to  prevent  or 
modify  the  approaching  disease.  Drugs,  of  course,  are  powerless  for 
this  purpose.  Is  vaccination  at  this  period  capable  of  exerting  any  such 
influence  ? 

From  the  clinical  reports  of  those  who  have  made  extensive  use  of 
vaccination  at  this  period  of  smallpox  there  seems  to  be  some  differences 
of  experience  concerning  its  efficacy.  In  commenting  on  this  question 
Curschmann  says:  "Are  we  able  to  exert  any  influence  on  the  disease 
in  the  early  stage  preceding  the  eruption?  Is  it  possible  in  infected 
persons,  during  the  stages  of  incubation  and  invasion,  to  cut  short  the 
disease  or  to  modify  its  course?  INIany  attempts  have  been  made  to 
answer  these  questions  affirmatively,  but  as  yet  without  much  result. 
The  first  idea  was  vaccination,  and  this  was  employed  by  some  in  the 
ordinary  way;  by  others  subcutaneous  injections  of  vaccine  lymph  have 
been  given,  it  is  said  with  good  results.     I  must,  however,  advise  great 

19 


290  SMALLPOX 

skepticism  regarding  these  assertions.  Of  the  subcutaneous  injection  of 
lymph  I  have  no  experience;  but  that  ordinary  vaccination  during  the 
stages  of  invasion  and  incubation  cannot  stay  the  disease  has  been  proved 
to  me  by  chance  observations  and  direct  experiments.  On  the  contrary, 
I  have  seen,  in  cases  in  which  vaccination  was  practised  after  infection 
with  variola,  vaccine  pustules  and  smallpox  pustules  developed  side  by 
side.  It  is,  in  my  opinion,  very  doubtful  whether  vaccination  can  even 
render  the  course  of  the  disease  milder." 

The  hypodermic  use  of  vaccine  lymph  is  certainly  not  entitled  to  any 
confidence  as  a  prophylactic  measure.  Immunity  does  not  result  from 
the  mere  presence  of  vaccine  virus  in  the  blood,  but  from  certain  unknown 
processes  which  take  place  in  the  system  in  the  course  of  true  vaccinia. 

It  is,  therefore,  evident  that  the  vaccine  disease  must  reach  a  certain 
stage  of  development  before  it  is  capable  of  exerting  any  prophylactic 
power  whatever.  We  have  had  very  frequent  opportunities  of  observing 
that  vaccination  during  the  invasive  or  initial  stage  of  smallpox  is 
utterly  valueless,  and  also  that  it  is  equally  useless  when  performed 
only  three  or  four  days  prior  to  the  earlier  invasive  symptoms.  A 
vaccine  vesicle  resulting  from  a  vaccination  performed  at  the  period 
just  mentioned,  and  the  variolous  pustules,  will,  it  is  true,  develop  side 
by  side  without  the  one  exerting  any  influence  whatever  over  the  other. 
But  Curschmann's  experience  seems  to  warrant  the  inference  that  at 
no  time  within  the  incubation  period  of  smallpox  can  vaccination  be 
used  with  advantage  against  the  approaching  disease.  If  such  is  his 
experience,  it  certainly  differs  very  greatly  from  our  own.  We  have 
in  numerous  instances  seen  smallpox  very  markedly  modified  by  vacci- 
nation performed  at  this  period,  and  not  infrequently  have  seen  it  pre- 
vented absolutely.  In  order  that  protection  shall  be  complete  it  is 
necessary  that  the  insertion  of  the  vaccine  lymph  should  be  made 
almost  immediately  after  the  reception  of  the  contagium;  but  if  made 
at  a  somewhat  later  date  a  modifying  efl^ect  may  still  be  obtained.  No 
part  of  the  incubation  period  should  be  considered  too  late  to  make 
use  of  this  remedy,  since  this  period  is  sometimes  prolonged  beyond  its 
usual  limits,  in  which  case  a  late  vaccination  may  prove  of  value. 

It  is  our  opinion  that  vaccinia  does  not  begin  to  exert  its  prophylactic 
power  until  the  areola  commences  to  form  around  the  vesicle.  At  this 
time  the  mild  febrile  reaction,  which  was  regarded  by  Jenner  as  a 
sine  qua  non  in  true  vaccinia,  becomes  apparent.  If  this  stage  of  the 
vesicle  be  reached  before  the  patient  shows  any  symptoms  of  smallpox, 
the  disease  may  be  entirely  prevented;  if  not  reached  until  after  the 
febrile  symptoms  appear,  but  before  the  eruption  occurs,  it  may  modify 
the  attack.  Now,  it  is  well  known  that  in  typical  vaccinia  the  areola 
appears  about  the  seventh  day  or  eighth  day  from  the  date  of  insertion 
of  the  lymph,  and  is  at  its  height  on  the  ninth  or  tenth  day;  and  it  is 
equally  well  known  that  the  incubation  period  of  variola  is,  in  the 
majority  of  cases,  of  ten  or  eleven  days'  duration,  and  that  the  eruption 
does  not  appear  until  about  three  days  later.  This  renders  quite  obvious 
the  fact  that  vaccination,  practised  shortly  after  variolous  infection  has 


77//';  rilKATMKNT  OF  SMAfJ.POX  291 

occurred,  has  an  opporditjity  in  [)()inl  of  lime  to  exert  more  or  less 
prophylactic  iiifhience  against  (he;  incuhaling(Jisease.  While  no  inflexi}>!e 
rule  can  be  laid  down,  it  may  be  said  in  a  general  way  that  if  vaccination 
be  practised  on  the  first  or  second  day  after  the  reception  of  the  infection 
into  the  systetn,  the  protection  may  })e  perfect;  and  if  errif>loyed  betv\(;cn 
this  date  and  the  fifth  day,  it  may  be  j)artial.  But  we  would  emphasize 
the  fact  that  after  infection  has  occurred,  every  day  that  is  allowed  to 
pass  before  resorting  to  vaccination  is  so  much  valuable  time  lost. 

While  the  appearance  of  the  areola  generally  indicates  the  period  of 
the  vaccine  process  at  which  its  prophylactic  power  ))egins  to  }je  exerted, 
yet  this  period  may  vary  somewhat  in  different  individuals.  For  instance, 
we  have  more  than  once  seen,  say,  two  persons  exposed  to  the  contagion 
of  smallpox  at  the  same  time  in  such  a  manner  that  there  could  be  no 
doubt  about  infection  having  occurred,  have  vaccinated  these  persons 
at  once  and  with  the  same  virus,  and  the  vaccinia  in  V)oth  cases  has 
pursued  an  identical  course,  yet  in  one  the  protection  was  perfect,  while 
in  the  other  it  was  only  partial.  In  other  similar  instances  one  has 
received  partial  protection  and  the  other  none  at  all.  This  difference 
is  doubtless  due  to  some  individual  peculiarity  that  cannot  be  explained. 

It  is  much  easier  to  confer  protection  against  smallpox  after  infection, 
where  revaccination  is  required  to  accomplish  this  result,  than  where 
the  vaccination  is  primary.  The  explanation  of  this  is  not  difficult.  It 
is  because  vaccinia  in  its  modified  form,  such  as  results  from  revaccina- 
tion, develops  more  speedily,  arrives  at  the  areolar  stage  more  quickly, 
and  runs  its  entire  course  several  days  sooner  than  does  the  unmodified 
or  true  vaccinia;  hence,  it  is  clear  that  the  period  of  protection  in  such 
cases  must  be  reached  earlier. 

In  endeavoring  to  confer  protection  during  the  incubation  stage  of 
smallpox  the  quality  of  the  vaccine  lymph  employed  has  a  great  deal 
to  do  with  the  success.  Nothing  is  of  more  vital  importance  at  this 
period  of  the  disease  than  that  the  vaccine  virus  employed  should  be 
fresh  and  active.  The  difference  between  success  and  failure  in  pro- 
ducing vaccinia  after  exposure  often  means  to  the  patient  the  difference 
between  life  and  death.  We  know  of  no  virus  more  reliable  or  which 
will  give  better  results  than  eighth-day  lymph  taken  directly  from  a 
typical  vaccine  vesicle  on  the  arm  of  an  infant. 

While  humanized^  virus  has  gone  out  of  use  in  most  countries,  we 
cannot  refrain  from  testifying  to  its  reliability  and  value  in  persons 
who  are  exposed  to  smallpox.  The  virus  of  long  humanization  possessed 
the  additional  advantage  of  running  a  rapid  course  and  so  bringing 
about  its  protective  influence  promptly. 

The  virus  resulting  from  a  long  series  of  human  transmissions  was, 
therefore,  to  be  preferred  over  virus  of  recent  humanization  and  animal 
virus.  At  the  present  time,  however,  we  are  more  concerned  with 
bovine  virus,  which  has  for  certain  reasons  largely  superseded  the  use 
of  humanized  lymph. 

1  Humanized  virus  is  still  extensively  employed  in  Mexico,  where  the  Iphysicians  prefer  it  to 
animal  lymph, 


292  SMALLPOX 

It  is  believed  by  some  authors  that  miihiple  insertions  quicken  the 
process  of  vaccinia,  and  thus  hasten  the  attainment  of  that  stage  of 
the  disease  at  which  its  prophylactic  poM^er  begins  to  be  exerted.  Water- 
house  was  of  this  opinion,  and  his  remarks  on  the  subject  are  interesting 
because  they  were  made  a  century  ago,  in  the  very  earliest  history  of 
vaccination.     He  wrote: 

"I  think  it  proper  to  publish  an  important  fact  for  which  we  are 
not  indebted  to  Europe,  namely.  If  a  person  he  inoculated  with  the 
kinepock  two  days  after  having  received  the  casual  infection  of  smallpox, 
the  kinepock  will  predominate  and  save  the  patient.  Nay,  I  will  go 
further  and  say  in  some  cases  three  days  posterior  to  infection  instead 
of  two ;  for  there  is  a  mode  of  expediting  the  operation  of  the  kinepock 
virus  by  increasing  the  quantity  of  matter  thrust  under  the  epidermis; 
and  it  appears,  from  experiment,  that  this  does  not  depend  so  much 
on  increasing  the  quantity  put  into  a  deep  puncture  as  it  does  on  the 
increase  of  infected  surface.  In  other  words,  you  may  expedite  the  pro- 
cess of  kinepock  inoculation  two  days  if  not  three,  if,  instead  of  two 
punctures,  you  make  sixteen  or  twenty;  .  .  .  and  on  the  sixth 
day  from  the  operation  we  shall  have  the  appearance  of  the  eighth 
day  in  ordinary  cases;  and  on  the  eighth  day  we  shall  find  the 
appearance  of  the  tenth,  and  so  on  with  the  febrile  symptoms,  in 
which  commotion  the  prophylactic  power  consists." 

As  there  is  nothing  at  this  stage  of  smallpox  of  greater  importance 
than  vaccinia  attended  by  prompt  and  speedy  development  of  the 
vesicle,  it  is  evident  that  the  virus  employed  should  be  selected  and  used 
with  the  greatest  possible  care  and  skill. 

It  is  well  under  these  circumstances  to  employ  an  active  virus;  the 
production  of  a  sore  arm  is  a  matter  of  but  little  importance  when  the 
exposed  individual's  life  is  at  stake. 

In  order  to  ensure  success,  it  is  advisable  to  employ  virus,  when 
possible,  from  more  than  one  source.  It  is  desirable  at  this  time  to  guard 
as  far  as  possible  not  only  against  failure,  but  also  against  a  vaccine 
disease  of  slow  progress.  A  tardy  vesicle,  or  one  that  is  slow  in  making 
its  appearance  and  late  in  arriving  at  maturity,  gives  no  assurance  of 
safety. 

In  recent  years  animal  lymph  has  been  brought  to  a  high  state  of 
perfection  by  the  admixture  of  glycerin.  We  have  found  glycerinated 
lymph  properly  prepared  and  preserved  to  be  more  likely  to  succeed 
and  also  more  speedy  in  its  action  than  the  dried  virus  on  ivory  points. 
Hence,  during  the  incubation  period  of  smallpox  glycerinated  lymph 
may  be  found  almost,  if  not  quite,  as  effectual  as  long  humanized  virus 
in  preventing  or  modifying  the  approaching  attack.  We  have  had 
extensive  opportunities  of  testing  its  power  in  this  direction  and  have 
been  well  pleased  with  the  results.  The  records  of  the  hospital  bear 
testimony  to  the  fact  that  during  the  recent  epidemic  of  smallpox  in 
Philadelphia  several  unvaccinated  persons  sent  in  through  error  of 
diagnosis  were  protected  absolutely  by  the  use  of  glycerinated  lymph. 
Where  the  protection  was  not  perfect  there  was  marked  modification 


Tlll<:  TREATMENT  OE  SMA/JJ'OX  2!i5 

proved  unavailing,  and  we  can  df)  notliin^  (norc  ;i(  this  stji^f  fli;in  ircai. 
special  symptoms  as  tliey  arise. 

The  popular  though  erroneous  nolion  of  piist  cfnliiiics,  lh;i(  if  is 
necessary  to  keep  the  pjitient  hot  and  swejiling,  slill  prevails  to  sf>me 
extent,  and  not  iid're(|uentiy  it  is  I'oinid  very  (HffienH  to  overcome  this 
prejudice.  On  the  contrary,  every  effort  should  Ix;  flirecled  tf)\vard 
keeping  the  patient  as  comfortable  as  possible,  and  exj^erience  shows 
that  a  bedroom  well  ventilated  and  having  a  temperature  of  from  0')° 
to  70°  F.  is  best  suited  for  this  purpose.  The  onjinary  febrifuge  mixtures, 
such  as  li(pior  ammonia'  acetatis,  litpior  ])otassi  citratis,  tinctura  aconiti, 
etc.,  may  be  given  in  suitable  doses  and  at  stated  intervals  We  are 
in  the  habit  of  using  the  following  formula: 

l;fe— Spirit,  ssther.  nitrosi, 

Syrup.  limonis Ctd    fSiv. 

Liquor,  ammonii  acetatis fSv. — M. 

Sig.— Give  2  to  4  fluidrachms  every  two  hours  in  a  little  ice-water. 

If  there  is  irritability  of  the  stomach,  the  effervescing  citrate  of  potas- 
sium may  be  preferable.  It  sometimes  happens  that  the  stomach  is 
very  irritable,  especially  in  children;  in  this  case  lime-water,  subnitrate 
of  bismuth,  aromatic  spirit  of  ammonia,  a  little  chloroform -water,  or 
any  other  drug  or  agent  known  to  be  of  service  in  this  condition,  may 
be  used.  The  swallowing  of  small  pieces  of  ice  will  often  give  relief 
when  everything  else  fails.  When  the  skin  is  hot  and  dry  and  the 
temperature  high,  frequent  sponging  with  cool  water  is  serviceable. 
Severe  headache  may  call  for  the  application  of  cold  water,  iced  com- 
presses, or  an  ice-bag  to  the  head.  These  need  not  be  feared  on  account 
of  the  popular  superstition  that  they  tend  to  suppress  the  eruption,  for 
such  is  not  the  case. 

Nervous  symptoms,  such  as  insomnia,  delirium,  and  convulsions,  are 
often  prominent  features  of  the  disease  and  demand  appropriate  treat- 
ment. Some  of  the  bromide  salts,  or  chloral,  given  either  separately 
or  in  combination,  will  usually  succeed  in  subduing  these  symptoms. 
For  the  convulsions  of  children  there  is  perhaps  nothing  more  effective 
than  chloral,  given  either  by  the  mouth  or  rectum.  When  given  by  the 
mouth  it  should  be  well  diluted,  since  it  is  very  irritating  to  the  throat, 
which  is  liable  to  become  implicated  in  the  variolous  process  quite 
early.  Warm  baths  are  also  very  useful.  There  is  another  nervous 
symptom  commonly  present  at  this  stage  of  smallpox,  and  that  is  pain 
in  the  back.  This  is  sometimes  so  distressing  as  to  call  for  measures 
of  relief.  When  the  stomach  is  retentive  Dover's  powder  may  be  given, 
or  some  one  of  the  analgesic  coal-tar  products,  now  so  frequently  used 
to  relieve  pain.  Sometimes  there  is  much  restlessness  and  general 
irritability;  in  such  cases  we  have  found  a  little  morphine,  combined 
with  the  febrifuge  prescription  above  referred  to,  to  act  most  happily. 

The  common  practice  of  applying  mustard  to  the  back  for  the  relief 
of  pain  or  to  the  epigastrium  to  lessen  gastric  irritability  cannot  be  too 
strongly  condemned,  since  the  variolous  eruption  always  appears  in 
much  greater  abundance  on  irritated  surfaces.     "\Mierever  there  is  an 


296  SMALLPOX 

ulcer,  a  wound,  or  an  excoriated  condition  of  the  skin,  there  the  pustules 
are  sure  to  be  found  in  dense  clusters.  We  have  frequently  seen  the 
eruption  intensely  confluent  over  regions  of  the  skin  where  a  mustard 
plaster  had  been  applied  during  the  initial  stage  of  the  disease.  Some 
have  thought  that  the  eruption  might  in  this  way  be  diverted  from  the 
face  to  other  localities,  but  we  are  convinced  that  it  is  not  diminished 
anywhere  else  by  reason  of  its  confluence  on  these  parts  through  the 
action  of  a  sinapism;  rather  is  it  increased  to  that  extent. 

The  digestion  at  this  §tage  is  not  vigorous;  hence  the  diet  should  be 
light  and  easily  assimilable.  There  is  nothing  more  suitable  than 
animal  broths  and  milk.  The  best  beverages  are  cold  water  and  iced 
lemonade.  Acidulated  drinks  seem  to  be  particularly  grateful  to  the 
palate.  Gentle  cathartics  may,  of  course,  be  administered  whenever 
indicated. 

3.  The  Eruptive  Stage.— The  eruptive  stage  may  be  said  to  comprise 
a  period  beginning  with  the  first  appearance  of  the  eruption  and  ending 
when  pustulation  has  fully  occurred.  The  duration  of  this  stage  in  variola 
vera  is  usually  seven  or  eight  days,  but  in  modified  smallpox  it  is  short- 
ened in  proportion  to  the  degree  of  modification.  The  great  desideratum 
for  this  period  of  the  disease  is  a  remedy  capable  of  diminishing  or 
modifying  the  cutaneous  manifestations,  for  there  is  no  doubt  that 
recovery  of  the  patient  almost  always  depends  upon  the  quantity  of  the 
eruption  and  the  length  of  time  consumed  in  running  its  course. 

Formerly  it  was  thought  that  some  modification  might  be  brought 
about  by  bloodletting,  but  experience  shows  that  the  most  confluent 
eruption  has  succeeded  the  most  vigorous  employment  of  the  lancet. 
It  is,  therefore,  worse  than  useless  to  bleed,  for  by  so  doing  we  expend 
power  that  will  be  required  later  on  to  repair  the  injury  done  by  the 
disease. 

The  treatment  during  the  eruptive  stage  of  smallpox  should  be 
directed  toward  alleviation  of  the  subjective  symptoms  and  the  correc- 
tion of  special  symptoms  as  they  arise.  Usually  it  is  not  until  the 
eruption  appears  that  the  disease  is  recognized  and  the  degree  of  severity 
prognosticated.  If  the  case  promises  to  be  at  all  severe,  all  flannel 
undergarments  should  be  at  once  removed,  and  the  hair  cut  close,  so 
that  the  head  may  be  kept  cool,  cleanliness  enforced,  the  risk  of  cellular 
inflammation  of  the  scalp  diminished,  and  a  better  opportunity  afforded 
for  the  employment  of  cold  applications  should  delirium  or  more  urgent 
brain  symptoms  arise. 

The  febrile  symptoms  which  usher  in  the  disease  now  usually  remit, 
but  increase  again  as  the  eruption  progresses.  For  this  condition  the 
remedies  already  mentioned  may  be  continued.  It  sometimes  happens 
in  a  depressed  condition  of  the  system,  particularly  in  children,  that 
the  extremities  and  even  the  surface  of  the  body  are  cool,  and  that  the 
eruption  is  too  slow  in  making  its  appearance.  In  such  cases  the  appli- 
cation of  heat  and  the  administration  of  hot  stimulating  drinks,  such  as 
hot  toddy,  may  be  of  service.  This  condition  in  children  is  apt  to  be 
associated  with  convulsions,  in  which  case  there  is  nothing  better  than 


77//';  THI'IATMKNT  OF  SMALLPOX  297 

a  warm  batli  f()llow(;(l  by  an  envclopineiil,  iti  vvann  blankets.  StioiiM 
the  convulsions  continue,  however,  cliloral,  by  eitlier  inonfli  or  n;(tnni, 
is  quite  sure  to  give  relief.  We  repeat  here  the  caution  not  to  fail  to 
dilute  the  chloral  freely,  for  the  throat  is  now  so  much  inv(;lve(l  in  the 
variolous  j)rocess  that  an  irritating  draught  may  give  rise  to  croupous 
symj)toins,  or  even  acute  (edema  of  the  glottis. 

Tkeatmiont  of  the  TtitioAT. — As  the  eruption  progresses,  not  only 
the  fauces,  but  the  soft  and  hard  palate,  the  buccal  mucous  membrane, 
the  larynx,  and  sometimes  the  trachea  also  become  more  or  less  involved 
in  the  process,  and  this  is  often  the  source  of  difficult  and  painful  deglu- 
tition. This  condition  requires  the  use  of  mouth  washes  and  gargles, 
such,  for  example,  as  those  containing  chlorate  of  potash,  boric  acid, 
glycerole  of  tannin,  tincture  of  myrrh,  etc.  We  have  found  the  milder 
demulcent  fluids  made  from  flaxseed,  gum  arable,  or  slippery-elm  bark 
particularly  grateful.  Of  these  none  is  more  relished  by  the  patient 
than  flaxseed  tea,  sweetened  with  white  sugar  and  acidulated  with 
lemon-juice.  Careful  and  frequent  cleansing  of  the  mouth  affords 
considerable  relief.  This  may  be  done  by  the  nurse  covering  her  index 
finger  with  a  piece  of  soft  linen,  dipping  it  into  a  solution  of  boric 
acid  with  glycerin  added,  and  then  thoroughly  and  carefully  cleansing 
the  entire  buccal  cavity. 

During  the  recent  epidemic  (1901-04)  through  which  we  have  passed, 
we  found  orthoform,  in  one-grain  lozenges,  useful  in  lessening  the 
distressing  soreness  of  the  throat  and  mouth.  In  severe  cases,  however, 
where  the  throat  was  covered  with  lesions  we  were  obliged  to  use  a 
cocaine  (1  per  cent.)  spray  in  order  to  lessen  the  pain  in  swallowing, 
and  thus  enable  patients  to  partake  of  sufficient  nourishment.  Variolous 
patients,  according  to  E.  Pepper,  who  advocates  cocaine  internally  in 
smallpox,  show  a  considerable  degree  of  tolerance  toward  this  drug. 
We  have  never  noted  untoward  results  from  the  employment  of  cocaine 
internally  or  in  spray  form. 

The  pain  in  the  throat  and  difficulty  in  swallowing  are  often  benefited 
by  having  the  patient  hold  in  his  mouth  small  pieces  of  ice,  and  allowing 
these  to  dissolve  slowly.  Where  there  is  much  glandular  swelling  the 
application  of  the  ice-bag  externally  will  be  found  useful.  Some  patients, 
however,  will  prefer  the  use  of  poultices  or  hot  fomentations.  When 
there  is  much  foetor  some  antiseptic,  such  as  carbolic  acid  or  permanga- 
nate of  potash,  may  be  added  to  the  mouth  wash  or  gargle.  We  have 
found  dilute  chlorine  water  to  answer  a  good  purpose.  Variolous 
glossitis  is  best  treated  by  mild  antiseptic  mouth  washes  and  the  use 
of  pellets  of  ice.  Should  acute  oedema  of  the  glottis  or  of  the  ary- 
epiglottic  folds  occur,  an  emetic  may  be  given  if  the  patient  is  not  too 
weak,  or  local  scarification  may  be  practised.  When  suffocation  threatens, 
tracheotomy  offers  the  best  if  not  the  only  chance  of  recovery. 

Treatment  of  Nervous  Sympto^nis. — Toward  the  latter  part  of  the 
eruptive  stage  of  variola  persistent  insomnia  and  delirium  often  occur. 
Wlien  this  condition  of  the  patient  is  attended  by  a  flushed  face  and 
bounding  pulse,  an  ice-bag  to  the  head  and  a  brisk  cathartic  may  be 


298  SMALLPOX 

of  service.  Tartar  emetic  and  sulphate  of  morphine,  in  doses  of  from 
one-eighth  to  one-half  grain  each,  will  often  produce  sleep  and  quiet 
the  delirium.  Morphine  is  a  most  valuable  drug  in  controlling  restless- 
ness and  inducing  sleep  during  the  pustular  stage  of  smallpox.  To 
accomplish  this  end,  it  is  sometimes  necessary  to  administer  a  half  or 
three-quarters  of  a  grain  of  the  drug  in  twenty-four  hours.  However, 
it  is  usually  well  borne  and  the  patients  are  almost  always  benefited 
by  its  use.  Large  doses  of  bromide  of  potassium,  or  chloral  freely 
diluted,  may  be  given,  and  repeated  if  necessary.  Some  care,  however, 
must  be  taken  not  to  push  these  remedies  too  far,  lest  the  patient  lapse 
into  coma  or  a  state  of  profound  prostration. 

Occasionally  the  delirium  is  of  that  violent  kind  which  the  older 
writers  styled  "delirium  ferox."  This  is  accompanied  by  a  wild  expres-' 
sion  of  the  countenance,  and  such  a  strong  tendency  to  escape  from 
the  attendant,  or  to  self-destruction,  that  too  much  care  cannot  be 
exercised  for  the  safety  of  both  the  nurse  and  the  patient.  We  have 
known  strong  and  muscular  patients,  while  in  this  state  of  mind,  to  knock 
the  nurse  down,  jump  out  of  the  window,  and  run  to  some  secluded 
place,  where  they  would  cunningly  secrete  themselves.  We  have  also 
known  patients  to  attempt  suicide  in  various  ways  while  the  nurse  was 
temporarily  absent.  The  necessities  of  the  case,  therefore,  often  require 
the  use  of  some  artificial  means  of  restraint.  For  instance,  a  wide  band 
of  stout  webbing  or  canvas  may  be  placed  loosely  over  the  patient's 
chest  and  secured  to  each  side  of  the  bed.  Smaller  bands  of  the  same 
material  may  be  fastened  to  each  wrist  and  ankle,  or  leather  wristlets 
and  anklets  may  be  used,  the  former  being  secured  to  the  sides  of  the 
bed,  and  the  latter  to  the  foot  of  the  bed,  allowing,  however,  a  little 
motion  of  the  limbs,  so  that  the  patient  shall  not  be  subjected  to  painful 
restraint.  In  the  mean  time  every  effort  should  be  continued  to  quiet 
the  delirium,  and  when  the  patient  refuses  to  swallow,  the  drugs  and 
nourishment  should  be  administered  by  the  rectum. 

It  is  deemed  appropriate  to  speak  of  the  treatment  of  hemorrhagic 
smallpox  under  this  head,  for  the  peculiar  manifestations  of  that  type 
of  the  disease  become  strikingly  apparent  during  the  eruptive  stage;  and, 
moreover,  it  is  rare  for  a  well-marked  case  to  live  beyond  the  limits  of 
the  vesicular  stage.  Treatment  is  of  little  avail  in  this  phase  of  variola. 
The  remedies  usually  employed  are  acids,  quinine,  ergot,  and  tincture 
of  chloride  of  iron;  but  these,  we  think,  are  prescribed  more  in  con- 
formity with  general  usage  than  with  the  expectation  of  obtaining  any 
real  benefit.  When  hemorrhage  takes  place  in  the  various  cavities 
or  internal  organs  of  the  body,  it  is  recommended  that  styptics  be 
employed,  together  with  injections  of  ice-water,  or  the  use  of  cold 
compresses  or  tampons,  although  it  is  admitted  that  the  beneficial 
effect  of  these  agents  is  very  slight.  Transfusion  and  hypodermoclysis 
with  sahne  solution  have  been  tried,  but  have  not  given  very  encouraging 
results. 

This  type  of  the  disease  in  varioloid  is  not  quite  so  significant  of 
danger  as  in  variola.    We  have  seen  a  few  hemorrhagic  cases  of  varioloid 


THE  TR.EA  TMENT  OF  SMA  LLPOX  299 

in  which  the  hoin()iThafi;o  fi'oiii  infernal  organs  was  not  very  [)rofuse 
or  protracted,  althouf^li  tlie  purjmric  s[)ots  were  well  rnarkecJ,  recover 
under  the  free  use  of  iron  and  stimulants.  In  these  cases  nourishment 
was  freely  taken,  prostration  was  at  no  time  profound,  and,  as  the 
patients  passed  favorably  tliron<i;li  the  crnptivc  stage  of  the  disease,  the 
petechias  gradually  disappeared  and  convalescence  became  establisherl. 

The  most  a])propriate  diet  during  the  eruptive  stage  of  varifjla  is  a 
liquid  or  soft  diet.  It  should  be  easy  of  digestion  and  very  nutritious, 
for  the  patient  has  yet  to  pass  through  a  severe  ordeal,  in  which  his 
power  of  endurance  will  be  tested  to  the  utmost.  Such  articles  as 
animal  broths,  milk,  and  eggs  may  be  freely  given.  Bread  may  be 
added  to  the  broths  or  to  the  milk,  or  it  may  be  given  in  the  form  of 
milk  toast.  In  varioloid,  the  appetite  during  this  stage  is  often  unaffected  ; 
such  patients  require  but  little  treatment,  and  may  be  allowed  almost 
perfect  freedom  in  choice  of  diet. 

4.  Stage  of  Suppuration. — The  indications  for  treatment  during  this 
stage  are  to  mitigate  the  fever,  to  disinfect  the  exudation  from  the  skin, 
to  relieve  the  dangerous  throat  symptoms,  and  to  resist  by  every  possible 
means  the  tendency  to  death  from  exhaustion.  If  the  patient's  life  can 
be  prolonged  through  this  stage,  his  chances  for  recovery  increase  with 
each  succeeding  day. 

The  febrile  reaction  which  had  abated  considerably  when  the  eruption 
first  appeared,  now  increases  to  a  notable  degree,  sometimes  reaching  a 
greater  elevation  than  existed  during  the  initial  stage.  In  variola  con- 
fluens  the  temperature  at  this  period  of  the  disease  usually  ranges  from 
103°  to  106°  F.  Various  drugs  and  other  means  have  been  employed 
for  the  purpose  of  reducing  the  intense  heat  of  the  body,  but  not 
one  of  them  has  given  results  entirely  satisfactory.  Quinine  has  been 
recommended,  but  in  order  to  exert  its  antithermic  properties  it  must 
be  given  in  doses  of  10  grains,  repeated  every  half-hour  or  hour  until 
40  grains  have  been  taken.  This  usually  produces  effects  so  unpleasant 
that  we  seldom  give  it  in  antipyretic  doses.  We  use  it,  however,  quite 
freely  as  a  tonic,  and  also  on  account  of  its  favorable  action  in  prevent- 
ing septicaemia.  Some  one  of  the  antipyretics  of  the  coal-tar  series 
may  occasionally  be  found  useful.  There  is  no  doubt  about  the  power 
of  either  antipyrin,  acetanilid,  or  phenacetin  to  reduce  temperature,  but 
we  do  not  feel  sure  that  the  use  of  these  drugs  in  all  cases  is  unattended 
with  risk.  However,  when  used  carefully  and  in  selected  cases  we  do 
not  think  the  risk  is  very  great.  We  have  found  the  administration  of 
phenacetin  in  2^  or  5  grain  doses,  when  the  temperature  is  high,  to  lessen 
the  fever  by  one  or  two  degrees,  without  producing  any  unpleasant  effects. 

Baths. — Cool  immersion  baths,  which  have  been  recommended  so 
highly  in  Germany  for  reducing  high  temperature  in  t^-phoid  fever, 
have  not  met  with  anything  like  the  same  favor,  even  in  that  country,  in 
the  treatment  of  variola.  Apart  from  the  difficulty  of  getting  a  patient 
in  the  pustular  stage  in  and  out  of  the  tub,  it  is  found  that  they  do  not 
afford  much  relief.  The  use  of  cold  compresses  and  of  cold  sponging  are 
more  easy  of  application  and  are  very  often  ser%^ceable.    We  have  seen 


300  SMALLPOX 

patients  temporarily  benefited  in  warm  weather  by  covering  them  with 
sheets  wrimg  out  of  cold  water,  but  usually  this  treatment  is  not  well 
borne  in  cold  weather.  Kaposi  recommends  the  use  of  compresses 
moistened  with  tepid  water;  the  choice  between  the  employment  of  cool 
or  tepid  water  should  depend  largely  on  the  season  of  the  year,  and  the 
sensations  and  temperament  of  the  patient. 

Continuous  warm  baths  are  often  of  great  value  in  the  treatment  of 
smallpox.  In  the  early  days  of  medicine  baths  were  employed  in  this 
disease  with  the  idea  of  hastening  the  appearance  of  the  eruption. 
With  this  end  in  view  Rhazes  advised  his  patients  to  be  kept  in  a  kind 
of  balneum  vaporis.  Hebra  advised  a  special  tub  for  treatment  by 
continuous  immersion.  He  had  previously  noted  the  good  effects  of 
this  procedure  in  extensive  burns  and  in  certain  cutaneous  diseases. 
He  remarks:  "I  have  found  by  experience  that  persons  may  remain  in 
a  warm  bath  a  hundred  days  uninterruptedly  day  and  night,  without 
injury  to  their  health."  His  object  in  treating  smallpox  by  this  method 
was  "by  thoroughly  soaking  the  pustules  to  favor  the  escape  of  their 
contents,  and,  at  the  same  time,  to  prevent  access  of  the  air  so  as  to 
render  it  impossible  that  any  decomposition  of  the  pus  should  take 
place." 

Stokes^  commends  the  use  of  the  warm  bath  and  presents  the  history 
of  a  medical  student  suffering  from  a  confluent  smallpox  with  hemor- 
rhagic tendency,  in  whom  this  treatment  was  employed.  The  patient 
was  immersed  for  seven  hours  and  the  procedure  repeated  on  the 
following  day.  Stokes  says:  "That  this  gentleman's  life  would  have 
been  sacrificed  but  for  the  timely  use  of  the  bath,  few  who  have  had 
any  experience  in  prognosis  can  reasonably  doubt.  He  was  in  the 
condition  of  a  patient  every  portion  of  whose  skin  had  been  burned  and 
ulcerated.  The  pustulation  was  almost  universally  confluent;  the 
purulent  matter  highly  putrescent;  the  hemorrhagic  state  developed, 
and  the  nervous  system  suffering — in  fact,  he  had  every  symptom  of  the 
worst  putrid  absorption." 

We  have  employed  the  continuous  warm  bath  in  smallpox  in  a  limited 
number  of  cases  and  have  been  favorably  impressed  with  its  therapeutic 
value.  The  cases  in  which  it  was  tried  were  desperate  types  of  confluent 
smallpox,  and,  although  we  were  unable  in  several  of  the  patients  to 
save  their  lives,  the  baths  conduced  much  to  their  comfort.  A  bath  of 
95°  F.  seemed  to  be  capable  of  reducing  a  temperature  of  104°  to  100° 
or  thereabouts  and  of  maintaining  the  temperature  at  about  this  level. 
With  the  reduction  of  the  fever,  the  pulse  decreased  in  frequency  and 
delirium  was  replaced  by  sleep.  We  kept  one  young  man  with  a  most 
severe  type  of  confluent  smallpox  in  a  continuous  bath  for  five  days. 
On  removing  him  from  the  tub  to  the  bed  at  the  end  of  this  time  his 
temperature  immediately  rose  from  100°  to  103°  F.  life  was  pro- 
longed in  this  case,  but  the  systemic  poisoning  was  too  profound  to 
permit  of  recovery. 

1  Some  Notes  on  the  Treatment  of  Smallpox,  Dublin  Journal  of  the  Medical  Sciences,  1872,  vol.  liii. 


THE  Tlil<:.\TMI<:NT  OF  SMAfJJ'OX  301 

Apart  from  the  antipyretic  infliieriec  of  tlio  eontinuoiis  warm  l^ath 
it  tends  to  macerate  the  pustules,  hastens  the  (Jiscliarj^e  of  tlieir  contents, 
and  thus  lessens  the  hahihty  to  secondary  pyogenic  infections  of  i\\<- 
skin.  We  have  found  tlie  onHnary  ward  tul)  with  an  ad  justa})le  crafJh; 
attachment  admirably  adiif)t(!(l  for  continuous  baths.  In  winter  hot 
water  must  be  frccjuently  ;ul(h'd  to  keep  the  temperature  up  to  the 
desired  degree.  When  the  teniperaturi!  of  the  water  falls  below  02° 
or  90°  F.  the  patient  will  usually  com])laiii  of  chilliness.  The  con- 
tinuous bath  treatment  re(|uires  the  services  <jf  a  special  attendant 
night  and  day. 

During  the  suppurative  stage  of  smallpox  the  vital  forces  of  the 
patient  are  put  to  the  severest  possible  test.  The  prostrating  effect  of 
the  septic  absorption  from  the  innumerable  pustules  must  be  necessarily 
very  great.  Watson  has  estimated  that  the  quantity  of  pus  in  the  skin 
amounts  to  quarts;  that  this  estimate  is  c[uite  accurate  is  evidenced  \)\ 
the  fact  that  we  found  the  amount  in  a  case  of  confluent  smallpox,  by 
actual  computation,  to  be  five  quarts.  So  extraordinary  a  drain  upon 
the  system  demands  that  the  strength  of  the  patient  should  be  vigorously 
supported;  otherwise,  evidence  of  exhaustion  soon  becomes  apparent. 

The  first  evidence  of  flagging  of  the  vital  powers  is  often  seen  in  the 
subsidence  of  the  redness  and  swelling  of  the  face  and  hands;  the  skin 
becomes  pale,  the  pustules  present  a  shrunken  or  collapsed  appearance, 
and  the  pulse  grows  rapid  and  feeble.  Other  symptoms  indicative  of 
exhaustion  are  subsultus  tendinum,  general  tremors,  a  dry  tongue,  and 
delirium.  These  are  always  indications  for  the  most  liberal  use  of 
stimulants  and  nutritious  and  easily  assimilated  food.  It  is  wiser, 
however,  not  to  wait  until  the  vital  energies  begin  to  flag  before  resorting 
to  supporting  measures.  As  the  patient  approaches  the  suppurative 
stage  his  strength  should  be  preserved  by  constant  reinforcement  so  as 
to  enable  him  to  encounter  the  struggle  that  is  to  follow. 

It  is  our  practice  to  commence  with  stimulants  and  nutrients  at  the 
beginning  of  the  suppurative  stage  or  earlier  when  deemed  necessary. 
The  method  of  their  employment  is  about  as  follows:  To  an  adult 
patient  suffering  from  the  confluent  variety  of  the  disease  we  direct 
that  there  shall  be  given  in  each  twenty-four  hours  not  less  than  two 
quarts  of  unskimmed  milk,  two  to  four  eggs,  and  six  to  twelve  ounces 
of  whiskey;  the  latter  being  given  usually  in  the  form  of  milk  punch. 
The  eggs  should  be  well  beaten  and  taken  with  the  milk  (a  little  salt 
being  added),  or  they  may  be  given  in  the  form  of  egg-nog.  It  is 
important  that  the  nutriment  be  given  at  short  intervals,  since  patients 
can  seldom  take  a  large  quantity  at  one  time.  It  is  also  important  that 
the  stimulants  and  nutrients  should  be  faithfully  continued  during 
the  night,  for  many  a  prostrated  patient  has  sunk  beyond  recovery 
between  midnight  and  morning,  for  the  want  of  these  measures. 

In  selecting  the  diet  and  stimulants,  we  should,  of  course,  take  into 
consideration  the  condition  of  the  patient's  stomach.  If  that  organ 
should  be  weak,  or  disinclined  to  receive  in  sufficient  quantity  the 
nutritive  material  just  referred  to,  or  if  there  should  be  a  great  repug- 


302  SMALLPOX 

nance  to  milk,  as  is  sometimes  the  case,  such  articles  as  bouillon  with 
eggs,  well-prepared  beef-tea,  nutritious  broths,  and  liberal  amount  of 
wine  should  be  given  instead.  As  a  stimulant  for  patients  in  profound 
prostration,  Curschmann  recommends  the  Stokes  cognac  mixture: 

^ — Cognac  optimi, 

Aquse  destillatse del    fSxv. 

Vitelli  ovi No.  1. 

Syrupi f5vj.-M. 

S. — A  tablespoonful  every  two  hours. 

We  would  suggest  that  this  preparation  might  prove  more  efficacious 
if  repeated  more  frequently,  or  given  in  larger  doses. 

In  the  way  of  drugs,  quinine  in  tonic  doses — 2  grains  every  three  or 
four  hours — is,  we  think,  of  service  at  this  stage  of  the  disease.  Digitalis 
seems  to  be  indicated  at  times  to  steady  the  action  of  the  heart,  but 
if  there  be  evidence  of  collapse  or  cardiac  failure,  carbonate  of  ammonium 
should  be  given  in  addition  to  the  alcoholic  stimulants,  together  with 
strychnia  hypodermically,  if  deemed  desirable.  Delirium,  which  is 
often  most  prominent  during  this  stage,  should  be  treated  in  the  manner 
already  described.  No  more  medicine  should  be  given  than  is  abso- 
lutely necessary,  for  the  less  the  stomach  is  taxed  with  the  ingestion  of 
drugs,  and  the  more  entirely  it  is  given  over  to  the  work  of  sustaining 
the  vital  forces  of  the  body,  the  better  will  be  the  chances  of  recovery. 

When  the  bowels  are  constipated  a  mild  laxative  may  be  administered, 
or,  what  is  preferable,  a  simple  enema  may  be  given. 

5.  The  Stage  of  Retrogression,  or  Stadium  Exsiccationis. — The  stage 
of  retrogression  is  characterized  by  drying  of  the  pustules,  lessening 
of  the  pain,  diminishing  of  the  swelling  and  redness  of  the  skin  and  of 
the  involved  mucous  membrane.  The  eyes  again  open,  the  nasal 
passages  become  more  patulous,  swallowing  is  less  difficult,  and  the 
countenance,  in  favorable  cases,  assumes  a  brighter  and  more  hopeful 
appearance.  This  stage  in  unmodified  smallpox  usually  begins  from 
the  eleventh  to  the  thirteenth  day  of  eruption,  and  runs  very  gradually 
into  the  stage  of  convalescence.  In  cases  somewhat  modified  it  com- 
mences a  little  earlier.  During  the  greater  part  of  this  period  the  same 
general  treatment  recommended  for  the  preceding  stage  should  be 
continued.  When,  however,  the  patient  shows  well-marked  indications 
of  improvement  the  quantity  of  stimulants  may  be  gradually  diminished, 
and  such  articles  as  corn-starch,  milk-toast,  soft-boiled  eggs,  cup  custard, 
and  the  like  may  be  added  to  the  diet.  Quinine  and  some  ferruginous 
preparation,  especially  the  tincture  of  the  chloride  of  iron,  are  particu- 
larly valuable  at  this  time. 

It  will  occasionally  be  found  necessary  to  administer  remedies  for  the 
relief  of  the  diarrhoea  which  may  develop  during  the  desiccative  stage. 
The  ordinary  drugs  employed  for  this  purpose,  opium,  the  astringent 
tinctures,  bismuth,  etc.,  will,  in  the  majority  of  cases,  succeed  in  quieting 
the  bowels.  Often,  however,  these  remedies  require  to  be  given  in  full 
doses  and  frequently  repeated. 

CEdema  of  the  feet  and  legs  is  not  infrequently  seen  after  severe 


77//';  Tia'JATMf'JNT  OF  SMMJJ'OX  303 

attacks  of  siniiH|)()X.  In  siich  fa.s(!S  tli(;r(;  is  alwiiys  'i;r(!at  cxlianstion  arifl 
the  patient  is  "(Mierally  aiia'inie.  'V\\i\  hitter  coiiditiori  is  douhtU-ss  the 
cause  of  the  a'derna  in  the  majority  of  cases.  In  tl)e  treatment  of  these 
cases  iron  in  some  form  should  be  administered,  and  a  rcjller  bandage 
applied  to  the  feet  and  lejijs.  If  the  kidneys  be  diseased,  they  shouhl 
of  course  receive  iij)proj)riate  treatment. 

The  various  c()m[)iications  of  smallixtx,  both  mcdic;d  ;ind  surgical, 
shoukl  be  treated  according  to  the  most  approved  methods,  it  being 
borne  in  mind,  however,  that  the  patient  is  suffering  from  an  exhausting 
disease  and  one  that  has  severely  taxed  the  integrity  of  the  important 
organs  and  tissues.  During  the  terminal  stages  of  the  disease,  tonics, 
particukxrly  those  containing  iron,  (piinine,  and  strychnine,  will  be 
found  extremely  useful.  Stimulants,  especially  in  the  form  of  malt 
liquors,  and  a  liberal  and  nutritious  diet  will  aid  in  restoring  strength 
and  weight  to  the  convalescent  patient. 

Liability  of  Error  in  Determining  the  Therapeutic  Value  of  Meas- 
ures Employed  in  Smallpox. — The  legion  of  remedies  and  specifics  of  all 
kinds  that  have  been  advised  and  used  in  the  treatment  of  smallpox 
bear  eloquent  testimony  to  their  inability  to  fulfill  the  extravagant  claims 
made  by  their  several  advocates. 

The  type  of  smallpox  has  been  very  considerably  changed  by  vacci- 
nation. Where  this  agent  does  not  confer  complete  immunity  against 
variolous  infection,  it  is  still  quite  sure  to  exercise  a  more  or  less  marked 
modifying  influence  over  the  disease,  according  as  the  period  at  which 
it  was  performed  is  near  or  remote.  Cases  of  smallpox  thus  modified 
may  assume  various  grades  of  severity,  from  the  mildest  possible  form 
to  that  barely  distinguishable  from  variola  vera.  But  even  where  the 
protective  influence  of  vaccination  seems  to  be  completely  lost,  there 
is  often  sufficient  of  this  influence  remaining  to  cause  a  slight  abridge- 
ment  in  the  course  of  the  disease,  and  thus  a  severe  case  is  often  helped 
through  to  a  favorable  termination.  It  is  therefore  easy  to  understand 
how  a  certain  drug,  or  some  special  method  of  therapeutics,  may 
acquire  an  unmerited  reputation  in  the  treatment  of  postvaccinal  cases 
of  smallpox.  In  determining  the  value  of  any  remedy  in  the  treatment 
of  this  disease,  conclusions  should  be  drawn  only  from  its  employment 
in  unvaccinated  cases.  Furthermore,  the  prevailing  type  of  the  epidemic 
should  not  be  left  out  of  consideration,  for  it  is  a  well-known  fact  that 
a  varying  percentage  of  cases  recover  in  different  epidemics.  Certain 
therapeutic  procedures  employed  during  mild  epidemics  may  be  accorded 
an  entirely  undeserved  commendation  and  value.  If,  during  the  uniquely 
mild  epidemic  of  smallpox  that  prevailed  in  many  parts  of  the  United 
States  from  1898  to  1905,  some  special  therapeutic  agent  had  been  advised 
and  generally  used,  there  would  have  appeared  no  more  incontrovertible 
fact  in  the  history  of  medicine  than  that  this  remedy  was  an  invaluable 
specific  in  the  treatment  of  smallpox.  And  yet  the  mildness  of  this 
widespread  epidemic,  with  a  mortality  rate  among  the  vaccinated  and 
unvaccinated  of  about  2  per  cent.  (/.  c,  during  the  first  two  years), 
was  not  influenced  to  any  appreciable  extent  by  any  therapeutic  meas- 


304  SMALLPOX 

ures.  Such  observations  serve  to  point  out  the  pitfalls  into  which  the 
ultra-enthusiastic  therapeutist  may  fall. 

It  must  be  reluctantly  admitted  that  there  is  as  yet  no  treatment  capable 
of  exerting  a  material  influence  in  either  shortening  or  modifying  the 
course  of  smallpox.  This  statement  must  not  be  interpreted  as  an 
indication  of  therapeutic  nihilism,  for  while  we  know  of  no  measures  of 
aborting  or  abridging  the  course  of  smallpox,  we  recognize  the  extreme 
usefulness  of  medicinal  treatment  directed  toward  the  relief  of  the 
symptoms  and  the  accompanying  complications. 

In  the  management  of  smallpox  greater  progress  has  been  made  in 
the  direction  of  prevention  than  cure.  Since  the  general  introduction 
of  vaccination,  epidemics  of  this  once  widespread  and  dreaded  scourge 
have  greatly  decreased  in  frequency  and  in  fatality. 

Unmodified  smallpox  has  always  been  an  extremely  difficult  disease 
to  manage,  and  the  treatment,  of  course,  has  varied  greatly  in  different 
epochs  of  medical  progress.  It  was  the  practice  for  centuries  in  the 
treatment  of  smallpox  to  repeatedly  bleed,  to  purge,  to  blister,  to  apply 
heating  lotions,  to  administer  heating  drinks,  to  cover  the  body  with 
heavy  bed-clothes,  and  to  carefully  exclude  from  the  bed-room  every 
breath  of  fresh  air. 

This  heating  method  of  treatment,  which  in  the  light  of  modern  ideas 
appears  almost  barbarous,  was  supplanted  by  a  directly  opposed  system, 
the  "cooling  regimen,"  inaugurated  by  the  celebrated  Sydenham,  and 
employed  with  good  results  to  the  present  day. 

Red-light  Treatment  of  Smallpox.— A  form  of  red-light  treatment 
of  smallpox  was  employed  by  John  of  Gaddesden,  in  the  fourteenth 
century,  and  doubtless  before  him  by  Arabian  physicians;  its  object 
was  to  excite  the  skin  and  cause  the  elimination  of  the  poisons  of  the 
blood.  John  of  Gaddesden,  though  court  physician,  is  said  to  have 
been  "a  very  sad  knave."  Gregory  wrote,  in  1843:  "What  think  you 
of  a  prince  of  royal  blood  of  England  (John,  the  son  of  Edward  the 
Second)  being  treated  for  smallpox  by  being  put  into  a  bed  surrounded 
with  red  hangings,  covered  with  red  blankets  and  a  red  counterpane, 
gargling  his  throat  with  mulberry  wine  and  sucking  the  red  juice  of 
pomegranates?  Yet  this  was  the  boasted  prescription  of  John  of 
Gaddesden,  who  took  no  small  credit  to  himself  for  bringing  his  royal 
patient  safely  through  the  disease."  Gregory  significantly  adds:  "Let 
us  then  avoid  the  errors  of  our  ancestors  without  reproaching  them." 

Picton,^  Black,^  Waters,^  Barlow,'*  and  others  have  employed  various 
methods  of  excluding  the  actinic  rays  of  light  in  treating  smallpox. 

Within  recent  years,  Finsen,  of  Copenhagen,  has  strongly  championed 
the  red-light  treatment  of  smallpox.  The  treatment  is  based  upon  the 
exclusion  from  the  sick-room  of  the  actinic  or  chemical  rays  of  light 
by  the  use  of  red-colored  screens  of  one  material  or  another.  Finsen,  in 
summing  up  the  cases  treated  by  this  method,  chiefly  by  Danish  and 

1  The  American  Journal  ot  the  Medical  Sciences,  1832. 

2  Lancet,  June  27,  1867.  »  ibid.,  February  4,  1871.  •*  Ibid.,  July  1,  1871. 


rHI<:  THMATMf'JNT  OF  SMAfJJ'OX  .*i05 

Norwegian  pliysicians,  says  that  out  of  a  total  of  110  fo  LjO  oases  of 
smallpox  in  1  case  only  was  the  method  inefficacious. 

In  the  winter  of  ]0()2  the  writers  treated  two  cases  of  \'!iiiol;i  in  ;i  vc<\ 
room  specially  arniiigef I  for  tlic  piirj)()S<',  will)  a})Sohitely  ncfjjative  results 
in  both.  One  patient  died  diirino-  tin;  suppurative  fever,  and  the  other 
was  badly  scarred. 

Dr.  Nelson  1).  IJrayton,  of  Indianapolis,  observed  IJOO  patients  treated 
in  red-light  wards,  with  results  no  different  from  those  obtained  in  day- 
light wards.  We  seriously  (piestion  the  assertion  that  the  exclusion  of 
the  actinic  rays  of  light  will  prevent  suy)puration  and  scarring  in  severe 
smallpox  in  unvaccinated  individuals.' 

Other  Highly  Vaunted  Remedies. — We  have  tried  a  considerable 
number  of  remedies  wJiich  have  been  highly  recommended  from  time 
to  time,  but  with  results  so  discouraging  as  to  lead  to  their  abandonment. 
Some  years  ago  the  sulphocarbolate  of  sodium  was  lauded  as  an  agent 
of  particular  value.  We  employed  it  in  seven  cases,  giving  it  in 
twenty-grain  doses  every  three  hours.  All  of  these  patients  died.  To 
be  sure,  they  were  all  severe  cases — all  of  them  confluent,  and  some 
malignant.  But  they  certainly  presented  a  class  of  cases  in  the  suc- 
cessful treatment  of  which  something  more  than  the  ordinary  measures 
are  required,  which  requirement  is  evidently  not  met  by  the  antiseptic 
properties  of  the  sulphocarbolate  of  sodium. 

In  a  well-known  text-book  on  cutaneous  diseases  it  is  stated  that  the 
internal  administration  of  the  hyposulphite  of  sodium  is  capable  of 
favorably  modifying  and  shortening  the  process  of  suppuration.  We 
have  given  this  drug  in  twenty-grain  doses  every  four  hours  day  and 
night  in  a  dozen  or  more  cases  without  observing  the  slightest  influence 
upon  the  course  of  the  disease. 

We  have  used  a  sixteenth  of  a  grain  of  bichloride  of  mercury  in  the 
tincture  of  the  chloride  of  iron  every  four  hours  in  scores  of  patients 
without  noting  any  particular  results  therefrom.  Even  in  the  late 
stages  these  drugs  do  not  seem  to  exert  any  influence  in  preventing 
the  formation  of  boils. 

The  favorable  reports  of  the  use  of  brew^ers'  yeast  in  furunculosis  and 
allied  conditions  prompted  us  to  test  its  value  in  the  treatment  of 
smallpox.  We  employed  it  in  about  forty  cases,  giving  it  in  two-drachm 
doses  every  four  hours,  day  and  night.  We  were  not  able  to  observe 
any  special  influence  from  its  use.  Neither  did  it  appear  to  prevent, 
to  any  appreciable  extent,  the  development  of  boils  and  abscesses. 
And  yet  a  French  physician,  who  recently  administered  yeast  in  a  few 
cases  of  smallpox  (in  patients  who  had  been  previously  vaccinated)  was 
encouraged  to  announce  his  belief  that  brewers'  yeast  given  early 
might  completely  abort  the  suppurative  stage  of  smallpox. 

Besides  the  drugs  mentioned  we  have  administered  a  few  other  anti- 

1  Since  writiug  tlie  above  we  have  noticed  an  article  on  "  Tlie  Red-Light  Treatment  of  Smallpox." 
in  tlie  London  Lancet,  July  tiO,  1904,  by  Drs.  Ricketts  and  Byles.  Thirteen  cases  of  smallpox  were 
treated  in  a  thoroughly  well-equipped  red-light  room.  The  writers  conclude  :  "We  cannot  agree 
that  the  treatment  has  any  of  the  merits  which  have  been  claimed  for  it." 

20 


306  SMALLPOX 

septic  remedies,  such  as  salicylic  acid,  salicylate  of  sodium,  and  carbolic 
acid,  but  we  cannot  say  that  we  have  seen  beneficial  results  from  their 
use.  With  xylol— which,  according  to  Zuelzer,  coagulates  the  contents 
of  the  pustules  and  cuts  short  their  development — we  have  had  no 
experience.  Others,  however,  do  not  seem  to  have  obtained  the  encour- 
aging results  which  were  claimed  for  this  drug. 

Serum  Treatment  of  Smallpox.^ — It  would  appear  from  experiments 
performed  by  Copeman,  Chauveau,  Beclerc,  Chambon  and  Menard, 
and  others,  that  the  serum  of  a  previously  vaccinated  heifer  is  capable, 
on  introduction  into  a  second  animal,  of  producing  a  certain  degree  of 
immunity  against  a  subsequent  vaccination. 

Prompted  by  this  result,  Beclerc  employed  such  a  serum  in  the 
treatment  of  a  woman  suffering  from  smallpox.  He  injected  the  enor- 
mous quantity  of  one  and  a  half  litres,  and  believed  that  the  serum 
produced  a  most  favorable  influence  upon  the  course  of  the  disease. 
Auche,  of  Bordeaux,  and  Landmann,  of  Frankfort,  employed  serum 
from  persons  who  had  passed  through  an  attack  of  variola.  The 
quantity  of  serum  injected  was  necessarily  small  and  no  appreciable 
results  were  obtained.  In  this  country  the  serum  treatment  has  been 
tried  by  Kinyoun  and  by  MacElliot,  the  former  claiming  a  successful 
result. 

The  authors  have  used  the  serum  of  vaccinated  heifers  to  a  limited 
extent  in  the  treatment  of  smallpox.  With  a  view  of  proceeding 
cautiously,  we  injected  only  a  small  quantity  (20  c.c.)  into  each  of  six 
patients.  The  serum  was  drawn  from  the  calf  twelve  days  after  vacci- 
nation. In  none  of  the  patients  was  there  any  perceptible  change  in 
the  course  of  the  disease.  One  patient,  a  lad  aged  fifteen  years,  received 
the  serum  before  the  appearance  of  the  eruption,  on  the  second  day 
of  the  initial  fever,  but  the  exanthem  appeared  and  progressed  in  the 
usual  manner.  We  had  intended  to  continue  the  experiments,  employ- 
ing much  larger  quantities,  but  a  large  bottle  containing  700  c.c.  of 
carefully  collected  and  prepared  serum  was  accidentally  broken,  and 
subsequently  our  supply  failed  us. 

Copeman  says,  in  regard  to  this  treatment:  "It  would  seem  probable 
that  no  really  useful  results  are  likely  of  accomplishment  until  we  are 
in  possession  of  some  more  satisfactory  method  of  immunizing  the 
system  of  the  animal  from  which  the  serum  is  derived.  Such  a  consum- 
mation can  only  be  expected  when  further  research  shall  have  provided 
us  with  reliable  methods  for  the  ready  cultivation  outside  the  animal 
body  of  the  microbe  specific  to  variola." 

Local  Treatment. — The  local  use  of  antiseptics  in  variola  has  been 
favorably  reported  by  various  writers.  Bianchi  praises  the  results 
obtained  from  the  following  treatment:  The  patient  is  first  bathed  in 
a  solution  of  1:20  of  boric  acid,  using  with  this  bath  antiseptic  soap. 
During  the  course  of  the  disease,  baths  in  the  boracic  acid  solution,  or 
in  a  solution  of  corrosive  sublimate  1 :  1000,  are  used  every  four  hours. 
After  each  bath  the  patient  is  anointed  with  iodoform  and  vaselin, 
from  1  to  5 :  100,  according  to  the  severity  of  the  case.     When  possible 


THE  TREA  TMENT  OE  >S'/lf /I  TJ.POX  307 

the  pustules  are  opened  with  uii  aseptic  needle  find  their  contents 
evacuated.  The  patient  is  then  wrapped  in  aseptic  linen,  which  is 
frequently  changed.  It  is  claimed  by  the  author  that  this  treatment 
notably  diminishes  the  duration  of  the  eruption,  lessens  the  fever, 
prevents  severe  ulcei'ation  and  scarring,  jind  (hus  leads  to  rapid  con- 
valescence. 

Similar  results  are  alleged  to  have  fcjllowcd  the  use  of  baths  contairiing 
permanganate  of  potassium,  the  salt  being  added  until  the  water  is  of 
a  rose-red  color.  Our  experience  with  permanganate  baths  has  been 
entirely  unsatisfactory.  The  baths  were  given  daily  and,  in  some  cases, 
twice  daily  from  an  early  period  of  the  eruption.  They  did  not  seem 
to  exert  any  favorable  influence  upon  the  course  of  the  eruption  or  the 
disease.  Indeed,  during  the  employment  of  this  treatment  our  mortality 
was  more  than  50  per  cent. 

Looking  back  over  the  literature  of  the  subject,  we  find  that  the 
antiseptic  treatment  of  smallpox  by  means  of  external  applications  is 
nothing  more  than  the  revival  of  an  old  practice  that  was  employed 
and  abandoned  many  years  ago.  It  is  true  that  when  these  agents 
were  used  a  half-century  and  more  ago,  it  was  not  because  they  possessed 
antiseptic  properties,  for  the  germ  theory  was  not  then  known;  but 
ignorance  of  this  fact  certainly  could  have  made  no  difference  in  the 
result.  As  long  ago  as  1843,  Gregory  wrote:  "The  latest  mode  of 
treating  the  surface  during  the  maturative  stage  of  smallpox  is  that  of 
applying  mercurial  plasters  containing  calomel  or  corrosive  muriate 
of  mercury,  or  covering  the  whole  surface  with  mercurial  ointment. 
In  the  French  hospitals  at  the  present  time  the  latter  mode  is  in  fashion. 
The  reports  which  have  reached  us  of  its  success,  however,  are  not 
very  flattering.  I  have  seen  all  three  plans  fairly  tried  at  the  Smallpox 
Hospital.  The  ointment  and  calomel  plasters  were  inefficient.  The 
plaster  of  corrosive  sublimate  converted  a  mass  of  confluent  vesicles 
into  one  painful  and  extensive  blister,  but  I  am  still  to  learn  what 
benefit  the  patient  derived  from  the  change." 

When  the  eruption  reaches  the  vesicular  stage  there  is  usually  experi- 
enced considerable  burning,  particularly  of  the  face,  hands,  and  fore- 
arms. For  the  purpose  of  preventing  or  alleviating  this  symptom,  some 
ointment  or  oily  substance  will  be  found  useful.  VaseUn  containing 
about  3  per  cent,  of  carbolic  acid  makes  an  efficacious  ointment;  or,  if 
the  odor  of  carbolic  acid  be  objectionable,  oil  of  eucalyptus  or  thymol 
may  be  substituted.  A  preparation  which  we  have  frequently  employed 
is  composed  of  equal  parts  of  lime-water  and  olive  oil,  to  w-hich  is 
sometimes  added  an  antiseptic  and  perhaps  a  Httle  cologne  water. 
This  is  freely  applied  with  a  large  camel's  hair  brush. 

When  the  burning  sensation  and  pain  are  severe  there  is  perhaps 
nothing  which  gives  so  much  relief  as  cold  applications,  such  as  cloths 
wet  with  cool  water  and  spread  over  the  face  and  arms.  Curschmann 
believes  that  cold  and  moisture  are  the  most  efficient  remedies  for  this 
condition.  He  says:  "In  severe  cases  the  application  of  iced  compresses 
to  the  face  and  hands,  or  to  any  parts  where  the  eruption  is  abundant, 


308 ,  SMALLPOX 

will  diminish  the  severe  pain,  lessen  the  swelling  and  redness  of  the 
skin,  and  make  the  patient  more  comfortable." 

Moore  advises  the  application  over  the  face  of  a  "light  mask  of  lint 
thoroughly  soaked  in  a  mixture  of  iced  water  and  glycerin  (a  table- 
spoonful  of  the  latter  in  an  ounce  of  water)  and  covered  with  oiled  silk." 

The  development  of  the  eruption  in  the  thick  skin  of  the  palms  of 
the  hands,  tips  of  the  fingers,  and  soles  of  the  feet  not  infrequently  gives 
rise  to  great  pain.  Cold  applications  or  iced  compresses  may  prove  of 
service  in  this  condition,  although  we  think  we  have  seen  greater  benefit 
follow  the  use  of  luke-warm  hand  and  foot  baths.  The  frequent  appli- 
cation of  flannel  cloths  wrung  out  in  tolerably  hot  water,  or  the  use  of 
hot  poultices,  is  often  of  great  service. 

The  topical  applications  recommended  for  the  pustular  condition  of 
the  skin  are  numerous.  To  assuage  the  pain,  burning,  and  itching,  to 
correct  the  offensive  odor,  to  guard  against  septicaemia,  and  to  pre- 
vent pitting  are  the  principal  ends  aimed  at  in  the  selection  of  these 
measures. 

During  the  period  of  suppuration  the  sensation  of  itching  is  quite  as 
intolerable  as  the  pain,  so  that  it  is  almost  impossible  for  the  patient 
to  refrain  from  scratching.  In  consequence  of  this,  or  from  other  causes, 
the  pustules  become  ruptured  in  many  localities  and  their  contents 
discharged.  This  purulent  material  undergoes  decomposition  and  gives 
rise  to  a  highly  offensive  odor.  Remedies  are  demanded  to  relieve  the 
itching  and  correct  the  odor.  Antiseptic  and  antipruritic  washes,  such 
as  carbolic  acid  (1:100),  or  corrosive  sublimate  (1:1000),  may  be 
employed  for  this  double  purpose.  About  the  mouth,  nose,  and  eyes  a 
saturated  solution  of  boric  acid  in  rose-water  may  be  freely  used.  We 
have  frequently  employed  a  5  per  cent,  solution  of  either  carbolic  acid 
or  Labarraque's  solution,  directing  that  both  the  patient  and  the  bedding 
should  be  sprayed  with  this  solution  every  two  hours. 

Very  excellent  results  are  said  to  have  followed  the  use  of  an  unguent 
composed  of  100  parts  of  cold  cream  to  4  parts  of  salicylate  of  sodium. 
M.  Dujardin-Beaumetz  reports  that  this  ointment,  in  his  hands,  has 
not  only  been  successful  in  destroying  the  repulsive  odor  in  severe  cases 
of  smallpox,  but  has  actually  prevented  suppuration.  In  addition,  he 
advises  that  a  powder  of  100  parts  of  talc  to  6  parts  of  salicylate  of 
sodium  be  dusted  over  the  affected  localities. 

We  have  sometimes  been  able  to  lessen  or  modify  the  horrible  odor 
by  using  as  a  dusting  powder,  subnitrate  of  bismuth,  boric  acid,  and, 
sparingly,  iodoform.  To  either  of  these,  and  especially  to  the  latter, 
talc  might  be  added.  We  have  also  derived  advantage  from  a  dusting 
powder  composed  of  15  to  20  parts  of  aristol  to  100  parts  of  talc. 

MacCombie  strongly  counsels  the  early  removal  of  the  crusts,  which 
he  asserts  can  best  be  accomplished  by  the  use  of  a  linseed-meal  poultice, 
sprinkled  with  iodoform.  "  On  the  face  the  method  most  agreeable  to 
the  patient  is  to  cut  a  mask  of  a  single  thickness  of  lint,  with  apertures 
for  the  nose,  mouth,  and  eyes;  then  to  smear  a  thin  layer  of  linseed-meal 
poultice   on  this,  taking  care  to  put   on  the  surface  a  little  vaselin  in 


Tflli  TRMATM/'JNT  OF  SMAfJJ'OX  .'{09 

wliich  iodoform  has  been  mixed,  and  to  apply  this  poulficc  <o  tlic  face, 
changing  it  at  least  every  two  hours."     (Moore. J 

Various,  indeed,  are  the  methods  that  have  been  i-('coiriiiicnd<-d  lor 
the  prevention  of  fiUing  in  smallpox,  and  yet  we  think  it  can  be.  truly 
said  that  no  one  of  them  has  stood  the  test  of  experience.  Vroui  the 
unmodified  form  of  the  disease  disfigurement  is  as  great  and  as  much 
dreaded  at  the  present  time  as  it  was  in  the  days  of  our  ancestors,  and 
it  seems  probable  that  this  will  continue  to  be  the  case  until  some  agent 
is  found  capable  of  causing  the  eruption  to  abort  l^efore  it  reaches  the 
pustular  stage,  for  the  suppurative  j)r()ccss  at  this  stage  is  attended  with 
destruction  of  cutaneous  tissue,  and  consequently  scarring  must  follow. 
If  any  ectrotic  measure  were  reliable,  it  would  be  easy  by  its  emyjloy- 
ment  to  limit  the  amount  of  cutaneous  inflammation  and  suppuration, 
to  lessen,  if  not  prevent,  the  so-called  secondary  fever,  aufl  thus  obviate 
the  danger  from  exhaustion.  Hence,  such  a  measure  would  serve  the 
double  purpose  of  preventing  pitting  and  saving  life. 

Of  the  various  ectrotic  measures  recommended  we  shall  refer  only  to 
those  which  are  spoken  of  most  favorably.  Opening  the  vesicles  with 
a  fine  needle  and  evacuating  the  contents  is  a  method  advocated  by 
Rayer  and  others.  Also  evacuation  of  the  vesicles,  foUow^ed  by  cauter- 
ization by  means  of  a  fine-pointed  stick  of  nitrate  of  silver,  has  been 
highly  recommended,  especially  by  Velpeau,  Bretonneau,  and  others. 
The  exclusion  of  light  and  air  from  the  skin  is  alleged  to  prevent 
pitting.  The  Egyptians  and  Arabs  sought  to  accomplish  this  by  cover- 
ing the  face  with  gold  leaf;  and  others,  more  recently  by  covering  the 
face  with  certain  dark-colored  plasters,  and  by  employing  red  light. 
Collodion  has  had  its  advocates,  and  a  solution  of  gutta-percha  in 
chloroform  has  been  recommended  by  such  authorities  as  Stokes, 
Graves,  and  Wallace.  In  using  either  of  the  two  latter  preparations 
it  is  advised  that  they  be  applied  to  the  face  once  or  twice  daily  with 
a  camel's  hair  brush,  and  that  the  applications  be  commenced  while 
the  eruption  is  papular,  or  while  vesicles  are  quite  small.  These  agents 
are  supposed  to  act  by  excluding  the  air  and  by  mechanical  pressure. 

Tincture  of  iodine,  applied  in  the  same  way  and  at  the  same  period 
of  the  eruption,  has  been  highly  recommended.  Sargent  is  said  to  have 
tested  the  ectrotic  power  of  this  agent  in  thirty  cases  of  smallpox,  the 
application  being  limited  to  one  side  of  the  face.  According  to  the 
description  given  of  the  resuUs,  there  was  not  so  much  swelling  where 
the  iodine  was  applied,  the  vesicles  were  flattened,  and  while  the  pitting 
was  not  prevented  it  was  perceptibly  diminished.  Lemaire  and  Sansom 
claim  to  have  used  successfully  carbolic  acid  diluted  with  alcohol.  This 
was  applied  as  soon  as  the  vesicles  began  to  assume  a  purulent  form. 
Certain  merit  has  been  claimed  for  subnitrate  of  bismuth  and  prepared 
chalk,  in  equal  parts,  when  applied  twice  daily  in  connection  with 
sweet  oil.  Sulphur  ointment  (from  1^,  to  2  drachms  to  1  ounce  of  lard), 
rubbed  lightly  over  the  affected  parts  three  times  daily,  has  been  recom- 
mended as  useful  in  preventing  suppuration  of  the  vesicles,  and  thus 
savins'  the  skin  from  disfio-urement. 


310  SMALLPOX 

Mercury  has,  perhaps,  been  more  highly  praised  than  any  other 
ectrotic  remedy.  It  has  been  employed  in  different  forms,  both  as  a 
plaster  and  as  a  wash.  M.  Briquet  was  in  the  habit  of  using  a  mask 
composed  of  mercurial  ointment  and  sufficient  powdered  starch  to 
solidify  the  mass,  so  that  it  could  be  moulded  to  the  various  parts  of 
the  face.  He  renewed  this  application  once  or  twice  a  day.  The  French 
physicians  have  been  very  partial  to  a  compound  mercurial  plaster, 
known  in  the  French  Pharmacopoeia  as  "plaster  of  Vigo."  It  has  been 
claimed  that  if  this  plaster  be  applied  over  affected  surfaces  before  the 
fifth  day  of  the  eruption,  the  papules  either  disappear  by  resolution  or 
change  into  vesicles  or  tubercles.  According  to  M.  Briquet,  the  latter 
change  seldom  takes  place  except  upon  the  face.  It  has  been  recom- 
mended that  the  plaster  be  kept  on  from  eight  to  twelve  days.  When 
removed  it  is  said  that  only  small,  hard  excrescences  are  seen,  and  that 
these  disappear  in  ten  or  twelve  days  without  leaving  any  scars.  It  is 
admitted  that  ptyalism  has  been  known  to  occur  from  the  use  of  this 
plaster.  Hence,  Bennett  was  led  to  substitute  for  the  mercurial  plaster 
calamine  saturated  with  olive  oil,  which  he  found  effective.  A  solution 
of  corrosive  sublimate  (1  grain  to  6  ounces  of  distilled  water,  with 
1  drachm  of  laudanum)  applied  by  means  of  compresses,  is  said  to  have 
caused  the  pustules  to  disappear  without  much  ulcerative  action.  This 
application  was  recommended  and  used  nearly  fifty  years  ago.  More 
recently  Niemeyer  recommended  the  employment  of  a  solution  of  about 
the  same  strength  (corrosive  sublimate  1  grain  to  water  6  ounces). 
Skoda  and  Hebra  advised  that  the  compresses  be  dipped  in  a  much 
stronger  solution  (grains  ij-iv  to  water  §vj).  Still  other  measures 
have  been  highly  lauded  for  this  purpose,  but  we  shall  not  consume  time 
and  space  by  referring  to  them. 

The  results  which,  in  our  experience,  have  followed  the  use  of  the 
so-called  ectrotic  measures  have  by  no  means  been  encouraging.  Perhaps 
one-half  of  our  patients  have  recovered  from  smallpox  without  permanent 
scarring,  but  the  result  in  these  cases  would  have  been  the  same  if 
simply  lard  or  cold  cream  had  been  applied  to  the  face,  or,  indeed,  if 
no  application  at  all  had  been  made.  In  the  severe  confluent  cases, 
no  remdy  has  been  successful  in  preventing  pitting,  although  we  have 
tested  practically  all  of  the  more  highly  recommended  measures. 

We  feel  strongly  inclined  to  agree  with  Gregory,  who  said:  "There  is 
no  peculiar  method  which  can  be  devised  for  the  prevention  of  pits  and 
scars.  The  masks  and  ointments  formerly  in  use  for  that  purpose,  and 
so  highly  vaunted,  are,  in  reality,  more  hurtful  than  beneficial.  The 
application  of  a  little  cold  cream  to  the  hardened  scabs  is  all  that  can 
be  recommended." 

We  have  had  the  skin  in  the  papular  stage  of  the  eruption  thoroughly 
washed  with  soap  and  water,  alcohol  and  ether,  and  bichloride  of 
mercury,  and  then  covered  with  ichthyol-collodion,  the  last-named 
application  being  applied  twice  a  day.  This  antiseptic  treatment  did 
not  seem  to  interfere  in  any  way  with  the  formation  of  the  pustules,  for 
they  grew  up  through  the  ichthyol  varnish. 


THE  TREA  TMENT  OF  SMA  LEPOX 


311 


The  remerly  which  appears  to  have  acconipljshcfl  most  in  our  hands 
is  the  tincture  of  iodine.  We  do  not  make  the  extravagant  claims  for 
this  application  that  some  writers  have  done,  but  we  do  think  that  it 
has  been  a  little  more  useful  than  anything  else  that  we  have  employed. 
Our  habit  has  been  to  paint  tlie  face  as  early  as  possible  with  the 
undiluted  tincture  of  iodine  and  to  continue  the  ay)j)licalion  once  or 
twice  a  day  according  to  the  sensitiveness  of  the  skin.  Most  j>atients 
bear  the  painting  very  well,  although  many  complain  of  smarting  for 
a  time  after  the  treatment.  In  some  patients  the  skin  is  so  sensitive 
that  this  mode  of  treatment  has  to  be  abandoned,  although  a  tincture  of 
one-half  the  usual  strength  might  })e  a])plied  in  such  cases.  AV)Out  the 
eighth  to  the  tenth  day  of  the  eruption,  in  unmodified  cases,  a  thin,  dry, 
parchmenty  mask  is  formed  wliich  begins  to  crack  and  peel  off.     At 


Fig.  53 


Showing  the  eftfect  produced  by  painting  the  right  arm  from  the  elbow  to  the  wrist  daily  wiih 
lincture  of  iodine.  Area  painted  is  free  of  the  secondary  impetigo  sores  seen  upon  the  untreated 
arm.    Left  arm  was  not  painted. 


this  time  it  will  be  found  advisable  to  substitute  an  unguentous  appli- 
cation. We  believe  that  the  iodine  treatment  tends  to  shrink  the  pustules, 
to  hasten  decrustation,  and,  to  some  extent,  to  lessen  the  pitting,  although 
in  severe  cases  it  will  not  prevent  it.  The  liability  to  consequent  pyogenic 
complications  of  the  skin  appears  to  be  diminished.  A  notable  feature 
of  this  treatment  is  that  it  completely  destroys  the  ofi'ensive  odor  arising 
from  the  areas  of  skin  to  which  the  iodine  is  applied. 

We  have  also  obtained  good  results  from  mild  emolUent  ointments, 
with  or  without  antiseptic  ingredients.  We  are  not  sure  that  any  special 
combination  is  essentially  more  useful  than  plain  petrolatum  or  cold 
cream.  In  the  early  stages  of  the  eruption,  these  applications  are  quite 
grateful  to  the  skin,  and  later  on  they  serve  to  soften  the  purulent 


312 


SMALLPOX 


debris,  which  can  then  be  more  easily  removed  from  the  face.  In  severe 
cases,  where  the  treatment  of  the  face  is  neglected,  the  odor  is  more 
offensive,  and  the  ulcerations  appear  to  be  deeper  and  followed  by 
more  disfiguring  pitting. 

We  have  frequently  incorporated  carbolic  acid,  aristol,  biniodide  of 
mercury,  etc.,  in  the  ointments  applied.     As  above  stated,  however, 


Fig.  54 


Smallpox  eruption  at  a  late  stage  shovviug  extensive  dark  crusting  on  the  face  resulting  from 
neglect  of  local  treatment. 


these  did  not  seem  to  materially  increase  the  efficiency  of  the  applications. 
To  soften  the  crusts  from  the  skin,  nothing  is  better  than  a  salve  of  the 
following  composition: 


p;— Sodii  bicarbonatis 5ij. 

Petrolati q.  s.  ad    gj. 

We  have  found  great  benefit  to  result  from  the  use  of  baths  given 
during  the  stage  of  pustulation  and  desiccation.    These  may  be  made 


TTiE  tI{.i<:atmi<:nt  of  smallpox  pap, 

antiseptic  by  tlic  addition  of  (Tcolin  (\  :F)(H))  or  hicliloride  of  niercury 
(1:J0,()()()  to  1:20,000).  The  piindent  accumulations  and  crusts 
are  detached  from  the  skin  by  the  baths,  and  the  associated  septic  fever 
is  greatly  lessened.  Furthermore,  the  liability  to  [)yogenic  skin  complica- 
tions is  diminished.  When  it  is  inconvenient  or  impossible  to  employ 
antiseptic  baths,  much  good  will  often  be  derived  from  oj^ening  and 
evacuating  the  pustules,  and  wasliing  the  bases  with  absorbent  cotton 
saturated  with  a  1. :  5000  solution  of  bichloride  of  mercury. 

When  extensive  impetigo  exists  we  employ  a  bichloride  bath  and  then 
dust  the  patient  with  a  weak  aristol  or  iodoform  talcum  powder.  An 
ointment  which  will  be  found  useful  in  treating  impetigo  pustules  is: 

1^ — Hydrargyri  iimmoiiiati gr.  x. 

Pulv.  amyli, 

Pulv.  zinci  oxidi dd  5ij. 

Petrolati Sss. 

Treatment  of  Eye  Complications.' — The  air  in  the  sick-room  or 
hospital  ward  should  be  changed  as  frequently  as  possible.  The  hands 
of  the  patient  should  be  encased  in  gloves  or  protective  bandages  to 
prevent  contamination  of  the  eyes.  As  a  matter  of  daily  routine  the 
eyes  should  be  flushed  copiously  with  warmed,  weak,  salt  or  boracic 
acid  solutions.  The  edges  of  the  eyelids  should  be  anointed  with 
vaselin.  In  all  examinations  of  the  eyes  great  care  must  be  used  in 
the  manipulation,  lest  the  cornea  be  injured. 

In  the  early  stages,  when  the  eyes  are  hot  and  flushed  and  feel  heavy, 
a  douche  or  spray  of  ice-cold  water  often  brings  relief.  In  excessive 
hyper?emia,  frequent  bathing  with  water  as  hot  as  can  be  borne  will 
have  a  soothing  effect.  In  other  cases,  cloths  saturated  w^th  lead-water 
and  laudanum,  or  ice-cold  compresses  may  be  laid  upon  the  closed 
lids. 

The  conjunctival  sac  should  be  frequently  flushed  with  warm  boracic 
acid  solutions.  At  bed -time  the  edges  of  the  lids  should  be  anointed 
with  vaselin,  or  with  yellow  oxide  of  mercur}^  in  vaselin,  1  grain  to  the 
drachm,  to  prevent  their  becoming  glued  together. 

When  conjunctivitis  sets  in  with  a  mucous  or  mucopurulent  discharge, 
mild  astringents  should  be  used;  saturated  solutions  of  boracic  acid, 
to  which  may  be  added  a  few  grains  of  sodium  chloride,  can  be  employed. 
The  lids  are  to  be  inverted  and  the  mucous  surfaces  painted  with  weak 
solutions  of  silver  nitrate  (1  to  5  grains  to  the  ounce)  or  protargol 
in  5  to  10  per  cent,  solution  may  be  satisfactorily  employed.  In  some 
instances  the  discharge  may  be  so  free  that  stronger  astringents  must 
be  used.  Here  no  more  efficient  remedy  than  silver  nitrate  can  be 
applied,  for  in  its  action  it  is  germicidal  as  well  as  caustic.  ^Mien  the 
lids  are  tense  and  board-like,  however,  and  their  mucous  surfaces 
covered  with  a  gray  film  or  false  membrane,  it  is  not  to  be  used;  but 
only  when  the  lids  are  relaxed,  the  discharge  creamy,  the  conjunctiva 

1  The  chapter  on  the  Treatment  of  Eye  Complications  has  heen  kindly  prepared  for  us  by  Dr. 
Buiton  K.  Chance,  whom  we  have  frequently  called  in  consultation  to  advise  us  iu  the  treatment 
of  severe  ocular  lesions  at  the  Municipal  Hospital. 


314  SMALLPOX 

red,  and  the  retrotarsal  folds  puckered.  After  thoroughly  cleansing 
them  the  conjunctival  surfaces  should  be  brushed  daily  with  strong 
silver  solution,  10  to  20  grains  to  the  ounce;  the  excess  of  the  drug 
is  to  be  washed  away  by  an  abundance  of  common  salt  solution. 

These  washiiigs  are  to  be  repeated  until  the  membrane  is  clear  and 
red,  and  as  long  as  the  discharge  is  abundant  the  use  of  silver  is  indi- 
cated. 

The  edges  of  the  lids  are  to  be  greased  with  vaselin,  and  they  are 
then  to  be  restored  to  their  normal  position.  The  pressure  on  the 
globe,  caused  by  the  swollen  lids  may  be  so  great  as  to  necessitate  the 
cutting  of  the  outer  canthus.  A  canthotomy  may  have  to  be  done  also 
to  facilitate  the  examination  of  the  conjunctiva  and  the  cornea. 

Persistent  and  increasing  chemosis  of  the  conjunctiva  demands  snip- 
ping in  order  to  relieve  the  pressure  on  the  cornea. 

When  the  lids  are  tense  and  the  secretion  flocculent,  the  local  applica- 
tion of  cold  is  most  useful.  The  readiest  means  of  applying  it  is  as 
follows:  Small  squares  of  lint  of  several  thicknesses  of  gauze  are 
placed  on  a  block  of  ice.  When  these  are  cold  the  excess  of  water  is 
squeezed  out  from  them  and  they  are  laid  on  the  swollen  lids.  They 
must  be  changed  sufficiently  often  to  maintain  a  uniform  coldness. 
In  some  cases  it  may  be  necessary  to  apply  them  continuously,  while 
in  others  they  need  be  used  for  short  periods  only  several  times  a 
day. 

When  the  cornea  is  involved  great  care  must  be  exercised  during  any 
manipulation,  lest  pressure  be  exerted  on  the  globe. 

Efforts  at  cleanliness  must  be  redoubled.  Solutions  of  atropine  of 
four  grains  to  the  ounce  are  to  be  used  twice  or  thrice  daily,  to  effect 
complete  mydriasis,  when  the  ulceration  is  central.  But  if  the  ulceration 
be  marginal  eserine  salicylate  in  weak  solution,  one-quarter  grain  to 
the  ounce,  may  be  used,  but  with  great  carefulness,  as  this  drug  is 
liable  to  increase  the  hyperaemia  of  the  iris,  with  consequent  iritis. 
Therefore,  the  use  of  this  drug  should  be  discontinued  when  the  pupil 
has  become  contracted.  Ice  must  be  discontinued  and  hot  compresses 
are  to  be  substituted.  Squares  of  gauze  wrung  out  of  water  w^hich  is 
kept  at  about  110°  F.  are  to  be  frequently  applied. 

Every  attempt  should  be  made  to  remove  all  of  the  discharges  and 
to  restore  the  conjunctiva  to  its  normal  condition.  The  lids  are  to  be 
separated  very  gently  and  all  of  the  tenacious  secretion  is  to  be  wiped 
off  with  swabs  of  cotton.  The  conjunctival  sac  is  then  to  be  flushed 
with  warm  boric  solutions.  This  attention  should  be  given  every  hour, 
or,  if  necessary,  at  even  shorter  intervals.  Although  other  stronger 
antiseptics  may  be  tried,  we  are  of  the  opinion  that  the  careful  and 
persistent  use  of  mild  boric  acid  or  weak  bichloride  of  mercury 
solutions  should  yield  the  best  results. 

Where  perforation  of  the  cornea  is  threatening,  the  edges  of  the  ulcer 
must  be  cauterized  at  once.  Here  a  dull  hot  probe,  thoroughly  applied, 
may  end  the  process.  We  have  used,  besides  the  hot  probe,  solutions 
of  carbolic  acid,  of  iodine,  and  crvstals  of  trichloracetic  acid.     If  there 


TJIli  Th'/'JATMKNT  OF  SMALLPOX  315 

1)6  not  too  Mincli  (•oiijiiiictiviil  swnitioii,  .'i,  well-applied  rf)llcr  hiiiida^^f 
may  ad'ord  the  pro|)er  sii})])oi't  to  the  already  w(;akeried  eorii(;al  ineirj- 
brane. 

A  low  ^ra,de  of  conjunctivitis  may  {)er,si.st  for  a  week  or  even  months 
after  convalescence  from  smallpox  in  persons  whose  illness  has  fjeen 
complicated  hy  serious  conjunctival  inflammation.  Here  the  use  of 
stimulatinfii;  astringents  like  the  boroglyceride  or  the  glycerole  of  tanrn'n 
act  with  signal  advantage.  Argentamin,  2  to  5  per  cent.,  or  largin, 
5  to  10  per  cent.,  may  be  tried. 

Formalin,  Ir.WOO,  or  bichloride  of  mercury,  three-quarters  of  a 
grain  to  the  pint,  may  be  used  with  success  in  more  severe  cases  with 
considerable  discharge. 


CHAPTER  VI. 

CHICKENPOX. 

Synonyms. — Varicella;  formerly,  Variola  crystallina,  Variola  nctha, 
Variola  spuria.  English,  formerly,  water  pock,  glass  pock;  German, 
Varicellen,  Wasserpocken,  Wind  hldttern,  Schafpocken;  French,  la  vari- 
celle,  la  verolette;  Italian,  Mcrviglicne,  ravaglione. 

Definition. — Chickenpox  is  an  acute,  highly  contagious  disease, 
occurring  chiefly  in  children,  characterized  by  an  eruption  of  vesicular 
type,  appearing  in  crops  and  accompanied  by  mild  febrile  disturbance, 
which  usually  begins  with  the  appearance  of  the  cutaneous  outbreak. 
The  lesions  dry  in  a  few  days  into  crusts.  One  attack  protects  for 
life  in  the  vast  majority  of  cases. 

History. — Chickenpox  is  doubtless  a  disease  of  great  antiquity, 
although  for  centuries  it  was  confounded  with  smallpox.  The  Arabian 
physician,  Rhazes,  who  lived  in  the  ninth  century,  made  mention  of  a 
mild  or  spurious  eruption  which  was  not  protective  against  epidemic 
smallpox.  The  Sicilian  physician,  Ingrassias,  seems  to  have  been  the 
first  to  have  described  varicella  in  accurate  terms;  this  appeared  in  a 
work  entitled  Preternatural  Swellings,  written  in  1553.  Vidus  Vidius, 
an  anatomist  and  physician,  wrote  some  forty  years  later,  employing  for 
varicella  the  term  crystalli  or  varioloe  crystallines ,  a  designation  which 
clung  to  the  disease  for  many  years. 

Sydenham  makes  no  mention  of  the  disease.  An  admirable  descrip- 
tion, which  admits  of  no  room  for  doubt,  has  come  down  to  us  from 
the  pen  of  Riverius,  who  wrote  in  1646. 

Morton's  writings  on  the  subject  are  of  historical  value,  because, 
according  to  Gregory,  he  remarks  that  the  disease  was  vulgarly  known 
as  chickenpox.  This  appears  to  be  the  first  mention  of  this  term  in 
literature.  The  name  chickenpox  is  said  to  be  derived  from  the  word 
cicer,  a  chicken-pea,  the  French  word  for  the  same  being  chiche.  Morton 
(1694)  referred  to  varicella  under  the  title  varioloe  admodum  henigna',  re- 
garding the  disease,  as  did  all  of  his  contemporaries,  as  a  variety  of  small- 
pox. In  1696  Harvey  contributed  some  important  writings  on  the  subject. 

Although  the  credit  of  recognizing  the  duahty  of  chickenpox  and 
smallpox  is  commonly  given  to  Heberden,  it  in  reality  belongs  to  Fuller, 
who,  in  1730,  expressed  his  views  in  the  following  interesting  language: 
"The  pestilence  can  never  breed  the  smallpox,  nor  the  smallpox  the 
measles,  nor  they  the  crystals  or  chickenpox,  any  more  than  a  hen  can 
breed  a  duck,  a  wolf  a  sheep,  or  a  thistle  figs,  and  therefore  one  sort 
cannot  be  preservative  against  any  other  sort."  ^ 

1  Quoted  by  Gee,  Reynolds'  System  of  Medicine,  American  edition,  1879,  p.  124. 


ciiiCKF.NPnx  317 

In  1707  irehordcn  rontribiitcd  to  tlio  flrsl,  volmrio  of  (ho.  Transactions 
of  the  Royal  dollccje  of  Physicians  a  carefully  [prepared  thesis  in  which 
he  urged  the  dissociation  of  smallpox  and  chickenpox.  He  employed, 
however,  the  unfortunate  title  of  variolw,  jmsilhr,  ignorin/^  the  term 
varicella  which  had  been  introduced  a  few  years  before  (1704)  by 
Vogel  in  Germany.  His  work,  though  at  first  strongly  criticized, 
became  for  many  years  the  acknowledged  classic  on  the  subject.  The 
term  varicella  is  a  diminutive  for  varus,  a  pimple. 

In  Germany,  Sennert  in  1676  was  the  first  writer  to  call  attention  to 
varicella.  In  Holland,  I)iemerl)roek  was  the  physician  to  achieve  this 
distinction.  In  the  following  century  the  most  important  literary 
contributions  were  made  by  Frank,  of  Vienna,  in  1805;  AVillan,  of 
London,  in  1806;  Heim,  of  Berlin,  in  1809;  and  Mohl,  of  Copenhagen, 
in  1817. 

In  1820,  Thomson,  of  Edinburgh,  obscured  the  comprehension  of  the 
disease  by  reasserting  the  old  doctrine  of  the  identity  of  variola  and 
varicella,  thus  leading  medical  opinion  into  one  of  those  by-paths  which 
so  constantly  cross  the  road  of  medical  progress. 

And  again  in  1866  there  appeared  a  champion  of  the  doctrine  of 
unity,  in  no  less  a  person  than  Ferdinand  Hebra,  the  great  Viennese 
dermatologist.  Hebra  regarded  varicella  as  a  mild  form  of  smallpox. 
He  wrote:  "I  apply,  then,  the  name  variola  vera  to  the  most  severe 
form  of  this  disease,  that  in  which  the  eruption  is  abundant  and  the 
fever  intense,  and  in  which  a  fatal  result  is  often  observed.  On  the 
other  hand,  I  use  the  term  varicella  for  cases  in  wdiich  the  rash  is  very 
scanty  and  which  run  a  favorable  course  and  always  terminate  in 
recovery."  And,  again,  "There  is  positive  proof  that  varicella  may 
generate  variola  or  varioloid,  and,  conversely,  variola  may  produce  in 
another  individual  varicella." 

When  it  is  remembered  that  mild  cases  of  smallpox  were  regarded 
by  Hebra  as  varicella  the  above  statements  need  occasion  no  surprise. 
It  is  difficult  to  conceive,  however,  how  a  close  observer  like  Hebra 
could  have  convinced  himself  that  there  was  no  chickenpox  distinct 
from  smallpox.  Hebra's  large  experience  in  smallpox  and  his  fame  as 
a  teacher  led  to  an  acceptance  of  his  view^s  in  many  quarters.  Cursch- 
mann,  writing  in  1875,  says:  "Concerning  the  relation  of  varicella  to 
variola,  no  perfect  unity  of  opinion  has  yet  been  reached.  While  Hebra's 
view  of  the  close  connection  of  the  processes  was  universally  respected 
until  a  short  time  since,  and  has  its  supporters  even  at  the  present  day, 
authoritative  voices  are  again  raised  in  favor  of  their  separation." 

Hebra's  views  were  taught  by  his  successor,  Kaposi,  until  his  death 
a  few  years  ago.  Kassowitz,  of  Vienna,  has  also  tenaciously  adhered 
to  the  view  of  the  identity  of  smallpox  and  chickenpox. 

It  is  remarkable  that  a  proposition  so  readily  capable  of  proof  as  the 
distinctiveness  of  smallpox  and  chickenpox  should  be  repudiated  by 
such  eminent  teachers  and  observers.  The  chief  explanation  of  the 
astounding  assertions  they  make  is  the  unwarranted  use  of  the  term 
varicella  to  designate  very  mild  cases^of  infantile  smallpox.    This  and 


318  "  CHICKEN  POX 

the  failure  to  recognize  chickenpox  as  a  separate  disease  account  for 
the  discrepancies  of  these  observers  as  compared  with  the  almost 
universal  teaching. 

With  these  few  exceptions,  physicians  throughout  the  world  are 
agreed  that  chickenpox  is  a  distinct  disease  having  no  relationship 
whatsoever  to  smallpox. 

It  would  be  an  act  of  supererogation  at  the  present  day  to  produce 
the  evidence  in  support  of  the  duality  of  these  two  diseases. 


ETIOLOGY. 

Age. — Chickenpox  is  essentially  a  disease  of  early  childhood.  It  is 
most  common  between  the  ag6s  of  one  and  seven  years.  Although  it 
develops  at  times  in  infants  at  the  breast,  they  more  commonly  escape 
the  infection  when  exposed  to  it.  The  statement  made  by  many  authors 
that  chickenpox  is  excessively  rare  in  adults  requires  qualification;  this 
view  has  been  so  commonly  held  for  many  years  that  we  have  deemed 
it  advisable  to  discuss  the  subject  of  adult  varicella  under  special  caption. 
We  have  within  a  few  years  seen  two  score  or  more  cases  of  chicken- 
pox  in  adults,  and  similar  experiences  have  been  recently  reported  by 
others.  The  most  advanced  age  at  which  we  have  seen  the  disease  is 
forty-nine  years.  The  youngest  period  at  which  varicella  appears  to 
have  been  observed  is  recorded  by  Senator,  who  saw  an  infant  of  eleven 
days  with  the  disease. 

The  following  table,  compiled  by  Gee^  from  the  records  of  the  Chil- 
dren's Hospital  of  London,  shows  the  age  incidence  among  children: 

Boys.  Girls.  Total. 

Under  1  month 2  0  2 

"       2  months 2  6  8 

"       3        " 4  9  13 

"  6         " 29  28  57 

"  12        " 45  52  97 

"  18        " 34  28  62 

"       2  years 36  39  75 

"       3      " 36  42  78 

"       4      "  ........  47  53  100 

"       5      " 44  52  96 

"       6      " 33  25  58 

"        7      " 19  11  30 

"       8      " 10  19  29 

"        9      " 4  6  10 

"  10      " 3  2  5 

"  12      " 1  6  7 

349  378  827 

Varicella  prevails  more  at  certain  times  than  at  others  and  may  occur 
in  epidemics.  In  large  centres  of  population,  however,  the  disease  is 
like  scarlet  fever,  endemic,  and  to  a  certain  extent  always  present. 
The  mildness  of  chickenpox  favors  its  dissemination,  inasmuch  as 
children  frequently  attend  schools  while  still  in  an  infectious  state. 

'  Loc.  cit. 


ETIOLOGY  ?AU 

Susceptibility  is  not  influencecJ  by  race,  tlic  negro  and  (he  C.'aucasian 
taking  the  disease  with  ecjual  facility.  Neither  does  varicella  seem  to 
be  influenced  by  climate  or  season. 

While  viiricella,  is  extremely  contagions,  its  infecting  [jower  is  not  as 
intense  as  that  of  measles  or  smallpox,  and  it  is  an  easier  disease  to 
control  by  isolation.  As  far  as  we  know,  the  infection  gains  entrance 
to  the  individual  through  the  respiratory  tract.  In  the  vast  majority  of 
cases  chickeiipf)x  is  contracted  by  direct  exposure  to  a  person  suffering 
from  the  disease.  It  is  not  impossibl'e  that  the  affection  may  be  carried 
by  a  third  person  or  through  the  agency  of  infected  objects,  but  this 
is  in  all  probal)ility  uncommon.  It  is  possible  for  the  disease  to  be 
transferred  before  the  appearance  of  the  eruption;  this  is  exemy)lified 
in  the  following  case: 

A  physiciaji's  daugliter,  aged  sixteen  years,  developed  a  slight  sore 
throat  and  a  little  fever,  and  was  isolated  in  a  room  in  the  upper  story 
of  her  home.  A  small,  whitish  patch  was  noticed  on  the  posterior 
pharyngeal  wall.  On  the  following  day  the  eruption  of  chickenpox 
appeared.  An  eight-year-old  brother  who  was  with  the  patient  on  the 
previous  day  was  kept  in  a  distant  part  of  the  house,  out  of  all  communi- 
cation with  the  sister  or  her  attendants.  Sixteen  days  after  exposure, 
the  same  having  taken  place  before  the  appearance  of  the  eruption, 
the  boy  developed  chickenpox. 

It  is  not  surprising  that  varicella  should  occasionally  be  communicated 
before  the  appearance  of  the  cutaneous  outbreak,  wdien  we  remember 
that  smallpox  may  be  transmitted  during  the  initial  stage  of  the  dis- 
ease. 

How  long  a  patient  remains  capable  of  transmitting  the  infection  has 
not  been  definitely  determined.  Nor  is  it  known  whether  the  infective 
agent  is  present  in  the  crusts,  as  is  the  case  in  smallpox.  In  the  absence 
of  positive  knowledge  on  this  point,  it  is  wise,  in  order  to  prevent  con- 
tagion, to  isolate  the  patient  until  the  skin  is  entirely  free  of  the  original 
crusts.  Crusts  due  to  secondary  infection  of  the  skin  are  not  capable 
of  transmitting  the  disease. 

Second  attacks  of  chickenpox  are  of  great  rarity.  Thomas  never 
observed  a  second  attack,  an  experience  which  corresponds  with  ours. 
Gerhardt  is  said  to  have  treated  a  child  with  three  attacks,  and  a  similar 
observation  is  recorded  by  Heim.  Vetter  states  that  he  saw  the  child 
of  a  physician  who  had  two  attacks  of  chickenpox  within  fourteen  days. 
Neale^  reports  a  second  attack  of  varicella  after  an  interval  of  ten  days. 
Trousseau,  Boeck,  Kassowitz,Huf eland,  and  Canstatt  have  also  reported 
cases.  These  isolated  instances  do  not,  however,  controvert  the  general 
experience  of  physicians  that  one  attack  of  chickenpox,  in  the  vast 
majority  of  instances,  protects  against  future  attacks. 

Inoculability  of  Varicellous  Fluid. — Numerous  investigators  have 
endeavored  to  determine  whether  varicella  can  be  communicated  by 
inoculation.     Willan  believed  that  the  disease  could  be  thus  trans- 

1  Lancet,  1S91,  ii. 


320  CHICKENPOX 

mitted,  but  Gregory  remarks  that  "his  experiments  are  few  and,  to  my 
mind,  unsatisfactory."  Bryce,  of  Edinburgh,  in  1816,  made  extensive 
trials,  with  negative  results.  He  states^  that  he  has  inoculated  with  the 
fluid  of  varicella  vera,  at  all  periods  of  the  disease,  and  at  all  seasons 
of  the  year,  children  who  had  never  undergone  either  smallpox  or 
cowpox,  and  yet  he  had  never  been  successful  in  producing  from  it 
either  variola  or  varicella. 

Delpech,  in  1843-44,  attempted  to  inoculate  patients  with  varicella 
at  the  Hospital  Necker  in  Paris,  but  with  unsuccessful  results.^  Hessa^ 
compiled  data  of  113  inoculations  with  varicellous  fluid;  in  87  of  these 
no  result  was  obtained,  in  17  there  was  merely  a  local  manifestation, 
and  in  9  cases  a  general  eruption  ensued.  Thomas  obtained  negative 
results  in  his  inoculations  and  mentions  the  fact  that  Heim,  Vetter, 
Czakert,  and  Fleischmann.  had  similar  experiences.  J.  Lewis  Smith 
in  this  country  likewise  failed  in  his  attempts  to  transfer  chickenpox 
to  children  who  had  never  had  the  disease. 

Steiner*  obtained  results  very  different  from  those  above  referred  to. 
He  claims  to  have  inoculated  ten  children,  eight  of  whom  developed 
typical  chickenpox.  The  time  elapsing  between  the  inoculation  and  the 
appearance  of  the  eruption  in  these  cases  was  eight  days. 

If  the  possibility  of  transmission  of  the  disease  in  the  usual  manner 
was  entirely  excluded  in  Steiner's  cases,  his  observations  go  very  far 
toward  proving  that  chickenpox  can  be  communicated  by  inoculation. 
In  view,  however,  of  the  negative  results  obtained  by  nearly  all  other 
investigators,  future  experiment  will  be  necessary  to  confirm  the 
successful  inoculations  obtained  by  Steiner. 

Period  of  Incubation. — The  stage  of  incubation  of  chickenpox  is 
ordinarily  longer  and  more  variable  than  that  of  smallpox  or  measles. 
Different  observers  assign  rather  variant  limits  to  this  period,  as  will 
be  seen  by  reference  to  the  following  quotations : 

Gregory^  says  "it  does  not  exceed  four  days  and  is  certainly  less  than 
a  week;"  Heberden^  places  it  at  eight  or  nine  days;  Trousseau,'^  "fifteen 
to  twenty-seven  days;"  Gee,^  "at  about  a  fortnight;"  Thomas,"  thirteen 
to  seventeen  days;  Delpech,  twelve  days;  Holt,^°  "quite  uniformly  from 
fourteen  to  sixteen  days;"  Corlett,^^  ten  to  nineteen  days. 

Our  experience  would  lead  us  to  regard  fourteen  to  seventeen  days 
as  the  usual  period,  although  we  have  observed  it  to  extend  over  nineteen 
days  and  even  as  long  as  twenty-one  days.  It  is  possible  that  in  rare 
cases  it  may  be  less  than  ten  days  and  longer  than  three  weeks. 

In  16  cases  occurring  in  an  outbreak  in  the  Municipal  Hospital  we 

1  See  Thomson  on  Varioloid  Diseases,  p.  74,  quoted  by  Gregory. 

2  Quoted  by  Gregory.  ^  Ueber  Varicellen,  Leipzig,  1829. 
1  Wiener  med.  Wochen.,  1875,  No.  16. 

5  Lectures  on  the  Eruptive  Fevers.    First  American  edition,  1851,  p.  295. 

6  Quoted  by  Gee.    Loo.  cit. 

^  Lectures  on  Clinical  Medicine.    American  edition.  Philadelphia,  1882,  p.  136. 

8  Reynolds'  System  of  Medicine.    American  edition,  Philadelphia,  1879,  p.  125. 

5  Ziemssen's  Encyclopedia  of  Medicine. 

10  Diseases  of  Infancy  and  Childhood,  p.  929.  "  Acute  Infectious  Exanthemata,  p.  165. 


H,YMI'T()MA  TOLOCIY  321 

were  able  to  fix  the  hiciihation  stage  quite  accurately.     Tlie  periofls 
were  as  follows: 

i:i  (lays  in  .  .  1  case.  1«  'lay.s  in  .  .1  case. 

14  "  .  .  7  cases.  !'••         "  ■  .    I    " 

15  "  .  .  3      "  'il          "  .  .     I     " 
17         "  .  .  2      " 

Stciiier,  who  claims  to  have  successfully  iuoculatefl  varicella  in  ei^'ht 
patients  found  the  incubation  stage  in  these  patients  to  be  uniformly 
eight  (lays.  During  the  incubation  period  there  are,  as  a  rule,  no 
evidences  of  disturbed  health.  Now  and  then,  however,  as  in  some  of 
the  other  exanthemata  the  breeding  of  the  disease  may  give  rise  to  slight 
symptoms,  such  as  loss  of  appetite,  lassitude,  and  general  inclisposition. 

SYMPTOMATOLOGY. 

Pre-emptive  Stage. — In  the  vast  majority  of  cases  chickenpox  is  not 
preceded  by  a  ])rodromal  illness.  The  onset  of  the  constitutional 
manifestations  is  usually  coincident  with  the  appearance  of  the  eruption. 
The  ordinary  history  elicited  from  mothers  is  that  the  eruption  is  the 
first  symptom  to  attract  their  attention,  and  that  the  children  are  not 
ill  prior  to  this  time. 

At  the  Municipal  Hospital  we  have  had  the  opportunity  of  studying 
the  temperature  records  of  a  number  of  chickenpox  patients  before  the 
appearance  of  the  eruption;  these  patients  were  convalescent  from 
scarlet  fever  when  they  developed  varicella.  In  almost  every  instance 
the  temperature  remained  about  normal  until  the  chickenpox  eruption 
appeared  and,  indeed,  in  some  cases  even  after  the  lesions  had  developed. 

In  a  small  percentage  of  cases  some  little  constitutional  disturbance 
may  be  observed  a  day  or  two  before  the  appearance  of  the  exanthem. 
This  consists  of  slight  rise  of  temperature,  anorexia,  vague  pains,  and 
chilliness.  More  common  is  it  to  discover  these  symptoms  a  half-day 
or  so  before  the  eruptive  outbreak.  During  the  night  preceding 
the  appearance  of  the  exanthem  the  child  may  be  slightly  feverish  and 
restless.  But  these  mild  precursory  symptoms  should  not  be  regarded 
as  representing  a  prodromal  illness,  for  by  this  term  as  applied  to 
smallpox  is  meant  a  distinct  stage  preceding  by  two  or  three  days  the 
onset  of  the  eruptive  phenomena. 

It  is  important,  however,  to  call  attention  to  the  fact  that  varicella 
in  adults  may  occasionally  be  preceded  by  a  prodromal  stage.  While 
most  of  these  patients  give  no  history  of  a  pre-emptive  illness,  a  minority 
of  them  will  volunteer  such  information.  We  have  seen  perhaps  a  half- 
dozen  of  adults  suffering  from  varicella  who  had  distinct  prodro- 
mata.  These  symptoms  consist  usually  of  chilliness,  lassitude,  anorexia, 
nausea,  slight  headache  and  backache,  and  some  elevation  of  temperature 
(101°  to  102°  F.).  These  manifestations  may  precede  the  appearance 
of  the  eruption  by  two  or  three  days,  though  more  often  not  longer 
than  twenty-four  hours.  It  is  rare  to  observe  high  fever,  vomiting, 
severe  lumbar  pain,  and  prostration — symptoms  which  usher  in  a  well- 
pronounced  smallpox. 

21 


322  CHICKENPOX 

In  general,  it  may  be  said  that  a  true  prodromal  stage  in  children 
suffering  from  chickenpox  is  extremely  rare;  in  adults  it  is  by  no  means 
so  infrequent.  When  it  does  occur  it  is  much  milder  than  the  prodromal 
illness  ordinarily  observed  in  smallpox.  A  prodromal  erythema  is,  in 
rare  cases,  seen  before  the  appearance  of  the  varicellous  eruption,  as  it 
is  at  times  before  the  eruption  of  smallpox  and  measles. 

Thomas  observed  "just  before  the  outbreak  of  a  light  case  of  varicella 
with  ephemeral  though  intense  fever  (105.8°  F.,  rectal  temperature)  the 
appearance  of  a  universal  erythema  of  short  duration."  He  adds, 
however,  that  although  he  watched  carefully  for  these  eruptions  this 
was  the  only  one  he  ever  saw. 

Henoch  is  also  said  to  have  seen  and  described  such  an  erythema. 

A  prodromal  scarlatinoid  rash  preceding  the  appearance  of  the 
varicella  eruption  was  observed  by  us  in  a  patient  admitted  into  the 
scarlet-fever  ward  of  the  Municipal  Hospital  in  the  early  part  of  1902. 
A  girl,  aged  five  years,  was  sent  to  the  hospital  from  a  large  foster 
home.  She  had  had  vomiting,  some  elevation  of  temperature,  and  on 
admission  there  was  a  diffuse  scarlatiniform  rash  covering  the  entire 
trunk.  This  resembled  scarlet  fever  so  strongly  that  an  experienced 
interne  regarded  it  as  the  scarlatina  exanthem.  The  rash  faded  in 
the  course  of  twenty-four  hours  and  was  followed  by  the  appearance 
of  a  number  of  varicella  vesicles.  At  the  end  of  five  days  after  admission 
to  the  ward,  a  rise  of  temperature  to  103°  F.  occurred,  accompanied 
by  sore  throat  and  a  well-pronounced  and  typical  scarlet-fever  rash. 
It  was  evident  that  the  child  contracted  scarlet  fever  in  the  ward.  No 
scarlet  fever  existed  in  the  foster  home  from  which  the  child  was  received. 

The  Eruptive  Stage.- — As  has  been  stated,  the  eruption  is  commonly 
the  first  symptom  to  attract  attention  to  the  disease.  Synchronously 
with  the  appearance  of  the  cutaneous  outbreak,  or  a  few  hours  before 
or  afterward,  a  varying  degree  of  fever  sets  in.  In  some  cases  this 
does  not  reach  higher  than  99°  F. ;  in  others,  however,  the  pyrexial 
elevation  may  be  most  marked.  Thomas  records  one  case  in  which 
the  initial  temperature  was  105.8°  F.,  and  we  have  on  several  occasions 
observed  temperatures  of  104°  and  105°  F.  This  high  fever  is,  as  a  rule, 
of  brief  duration,  subsiding  in  twelve  or  twenty-four  hours  to  99°  or 
100°  F.  High  fever  does  not  necessarily  presage  the  development  of  a 
profuse  eruption.  We  have  seen  a  temperature  of  104°  in  a  case  with 
scant  and  abortive  lesions. 

The  temperature  commonly  falls  to  normal  in  the  course  of  one  to 
three  days.  Where  the  eruption  is  copious,  however,  moderate  fever 
may  persist  for  four  or  five  days.  In  cases  in  which  the  varicellous 
lesions  become  secondarily  infected,  the  temperature  may  continue 
above  normal  for  a  fortnight  or  even  longer. 

The  Eruption. — The  eruption  of  chickenpox  usually  appears  first  on 
the  back  or  the  face,  although  other  regions  may  be  the  seat  of  the 
initial  lesions.  Irregular  extension  then  occurs,  new  lesions  developing 
on  different  portions  of  the  cutaneous  surface.  The  hairy  scalp  is 
nearly  always  beset  with^some  vesicles. 


SYMPTOM  A  TOLOaV  323 

The  distribution  of  ilic  eruption  is  subjec^t  to  soino  varialioii,  hut  is 
tolerubly  uniform  in  the  majority  of  cases.  'J'fie  trunk,  particularly  the 
hack,  is  relatively  more  profusely  attacked  than  the  distal  portions  of 
the  extremities — the  wrists,  ankles,  hands,  and  feet.  The  face  usually 
presents  a  moderalo  iiumhcr  of  discrete  vesicles.  It  is  rare  for  the 
face  to  escape  coiiij)lc(cly,  altlioiif^h  at  times  hut  two  or  three  lesions 
may  he  present.  At  other  times,  in  copious  eruptions,  quite  an  al)und- 
ance  of  lesions  may  he  seen  on  the  face.  The  arms  and  legs  are  seldom 
j)rofuscly  attacked  except  in  unusually  extensive  cases. 

It  has  heen  clainicd  hy  some  writers  that  varicellous  lesions  do  not 
occur  upon  the  palms  and  soles.  It  is  true  that  in  most  cases  the  palmar 
and  plantar  surfaces  are  free  of  eruption;  hiit  it  is  hy  no  means  rare 

Fig.  55 


Chickenpox  lesions  in  the  crusted  stage,  about  the  fourth  day  of  the  disease. 

to  find  a  few  vesicles  in  these  regions,  and  in  severe  cases  the  lesions 
may  be  fairly  numerous. 

The  palms  and  soles  are  much  less  frequently  and  less  abundantly 
involved  than  in  smallpox,  in  which  disease  some  lesions  are  nearly 
always  present  in  these  regions.  The  dorsal  surfaces  of  the  hands  and 
feet  are  likewise  relatively  lightly  affected  compared  vnth  the  general 
extent  of  the  eruption.  In  fact  it  may  be  stated  that  the  distal  portions 
of  the  extremities  usually  suffer  but  little  in  chickenpox;  the  eruption 
prefers  the  covered  surfaces. 

The  distribution  of  the  eruption  may,  to  some  extent,  be  influenced 
by  ixritation  of  the  skin  prior  to  the  appearance  of  the  lesions.  We 
have  seen  a  profuse  crop  of  lesions  develop  over  a  rectangular  area 
on  the  sternum  to  which  a  mustard  plaster  had  been  applied  during 
the  pre-eruptive  period.     Any  irritant  by  increasing  the  vascularity  of 


324  CHWKENPOX 

the  skin  may  attract  lesions  to  the  region  thus  irritated.  It  is  not  so 
common,  however,  to  observe  an  increase  of  the  eruption  from  this 
cause  as  it  is  in  smallpox.  In  the  latter  disease  the  influence  of 
cutaneous  congestion  in  determining  an  increase  of  the  eruption  in  a 
given  area  is  emphasized  by  frequent  experience. 

Ordinarily  by  the  time  that  the  physician  is  called  to  see  a  child  with 
chickenpox  vesicles  are  observable  upon  the  body.  If  the  skin  is 
carefully  examined  early  it  will  be  noted  that  the  vesicles  are  usually 
preceded  by  erythematous  spots.  These  are  pea  to  bean  sized,  rosy 
red  in  color,  and  in  appearance  not  unlike  the  rose  spots  of  typhoid 
fever,  or  fleabites.  Very  soon  the  centres  of  the  macules  become  raised 
and  small  vesicles  are  formed  which  rapidly  increase  in  size.  In  some 
cases  the  rosy  macules  are  elevated,  somewhat  acuminated,  and  in 
reality  represent  papules. 

The  duration  of  the  transitional  lesions  before  vesiculation  takes 
place  is  extremely  variable.  At  times  some  of  the  lesions  of  varicella 
abort  in  the  macular  or  papular  stage  and  never  go  on  to  the  develop- 
ment of  vesicles.  Indeed,  Thomas  mentions  a  case,  the  nature  of  which 
was  verified  by  the  previous  occurrence  of  varicella  in  a  sister,  in  which 
erythematous  spots  (roseolse)  persisted  for  thirty-six  hours  and  then 
disappeared  without  the  formation  of  any  vesicles  whatever.  Varicella 
without  the  development  of  vesicles  must,  however,  be  extremely  rare. 

Varicellous  vesicles  may  spring  up  so  rapidly  that  they  appear  to 
arise  directly  from  the  normal  skin.  We  were  enabled  to  determine 
in  one  instance  that  vesicles  developed  in  less  than  four  hours.  A 
trained  nurse  bathed  a  child  at  11  a.m.  and  carefully  examined  the 
skin  for  an  eruption  v/ithout  discovering  any.  At  3  p.m.,  four  hours 
later,  we  examined  the  child  and  found  several  fully  formed,  tense, 
varicellous  vesicles  on  the  trunk. 

The  lesions  often  look  as  if  they  had  been  produced  by  drops  of 
scalding  water  sprinkled  upon  the  skin.  They  are  superficially  situated, 
differing  in  this  respect  from  the  deeper-seated  vesicles  of  smallpox. 
The  epidermal  roof  of  the  vesicle  is  thin  and  readily  ruptured. 

The  vesicles  of  chickenpox  vary  greatly  in  size;  they  may  be  no 
larger  than  a  pinhead,  or  they  may  reach  the  dimensions  of  a  large  pea. 
They  are  commonly  tense,  although  rarely  as  hard  as  the  variolous 
vesicle.  Slight  traumatism,  such  as  is  produced  by  scratching  or  the 
friction  of  clothing,  sufifices  to  rupture  the  vesicle.  The  fluid  from  an 
early  vesicle  is  clear  and  watery  in  appearance;  later  it  becomes  turbid 
or  lactescent.  The  vesicles  are  round  or  oval,  the  shape  being  some- 
what determined  by  the  lines  of  cleavage  of  the  skin.  In  the  axillary 
and  lateral  costal  regions  they  are  commonly  oval,  the  long  axis  corre- 
sponding with  the  direction  of  the  ribs. 

Chickenpox  vesicles  are  commonly  surrounded  by  a  reddish  areola. 
This  may  be  narrow,  measuring  but  an  eighth  of  an  inch;  in  other  cases, 
however,  it  may  have  a  breadth  of  a  half -inch  or  more. 

Much  diagnostic  value  has  been  attributed  by  some  observers  to 
the  comparative  degree  of  evacuation   of  chickenpox  and   smallpox 


PLATE  XL. 


A  Severe  Attack  of  Chiekenpox,  showing  Lesions  in  Various 
Stages  of  Development  (fourth  day).  Relative  sparsity  of  lesions 
on  the  face  as  coin  pared  with  the  trunk. 


HYMI'TOMA  TOI/XiY  ;i2o 

vesicles  effected  by  })uncturin^  llicin  willi  ii  nccHlc.  While-  il  is  tnie 
tliat  the  varicella  vesicle  is  often  coiiiplclctly  crnpficd,  aiul  the  variolous 
vesicle,  owiiif^  to  its  more  niultilociilar  striicliire,  less  cotripletely  evao 
uated,  hut  little  value  should  be  phu-ed  upon  this  test.  There  is  too 
much  latitude  j)ossibIe  in  the  iiiterprcliilion  of  the  deforce  of  evacuation 
effected.  s 

The  eru|)tion  of  chickcii])ox  ii,j)pcafs  in  crops-.  'J'he  first  outbreak 
couiinonly  consists  of  a  do/en  to  fifteen  lesions.  After  an  interval  of 
some  hours,  usually  a  day  or  so,  a  second  crop  appears  which  often 
numerically  exceeds  the  first.  Twenty-four  hours  later  a  third  out- 
break may  occur  and  new  lesions  may  thus  continue  to  appear  for  four 
or  five  days  or  even  a  week.  Owinfi^  to  the  fact  that  the  lesions  are 
of  ditt'erent  age,  they  are  seen  in  varying  stages  of  evolution  and  invo- 
lution. There  may  be  present  at  the  same  time  small,  new,  tense  vesicles ; 
older,  drying  vesicopustules,  and,  in  addition,  dark-colored  cni.sts 
which  represent  the  remains  of  the  first  vesicles.  This  multifoi-mity 
is  one  of  the  most  distinguishing  features  of  the  eruption  of  chickenpox. 

The  duration  of  the  individual  lesions  of  chickenpox  is  brief.  The 
vesicles,  after  reaching  the  acme  of  their  development,  become  flaccid, 
and  in  from  one  to  three  days  dry  into  crusts.  The  unruptured  vesicle 
desiccates  first  at  its  central  summit.  Lesions  which  are  ruptured  by 
mechanical  force  give  exit  to  a  fluid  which  forms  an  irregularly  shaped 
crust. 

The  fluid  contained  in  the  vesicle  is  at  first  as  clear  as  w-ater;  it  later 
becomes  turbid  and  finally,  if  unruptured,  quite  purulent.  During  these 
changes  the  vesicle  which  has  in  the  beginning  a  "dewdrop-like" 
appearance  acquires  a  grayish  or  yellowish  color. 

True  umbilication,  such  as  is  seen  in  the  early  smallpox  vesicle,  does 
not  occur  in  chickenpox.  There  is  sometimes  seen  a  pinpoint-sized 
invagination  of  the  surface  of  a  vesicle  due  to  the  presence  of  a  hair 
follicle.  Commonly  there  is  observed  a  central  sinking  in  of  some  of 
the  vesicles  or  vesicopustules  due  to  partial  evacuation  and  central 
drying.  This  is  also  seen  in  the  late  pustular  stage  of  smallpox,  and 
might  be  called  a  secondary  umbilication. 

As  the  vesicles  of  chickenpox  begin  to  dry  there  not  infrequently 
develops  a  flat,  vesicular,  spreading  ring  upon  the  border  of  the  crust; 
beneath  the  raised-up  epidermis  is  a  little  puriform  fluid.  The  lesions 
may,  as  a  result  of  this  process,  spread  to  the  size  of  a  silver  quarter 
or  half  dollar.  This  condition  is  extremely  common  in  smallpox  and 
has  been  called  "impetigo  variolosa."  The  process  being  the  same 
in  chickenpox,  the  condition  might  be  appropriately  designated  "impetigo 
varicellosa."  The  cause  of  these  spreading  sores  is  an  infection  of  the 
varicellous  sites  with  streptococci  and  staphylococci  present  upon  the 
surface  of  the  skin.  In  extensive  eruptions  where  there  is  much  of 
this  impetigo,  moderate  elevation  of  temperature  may  develop,  giving 
rise  to  a  secondary  fever. 

The  extent  of  the  varicellous  eruption  is  extremely  variable.  The 
total  number  of  lesions  in  some  cases  mav  amount  to  but  a  half-dozen; 


326  CHICKENPOX 

on  the  other  hand,  they  may  cover  almost  completely  the  entire  cutaneous 
surface  and  number  hundreds  or  even  thousands.  Thomas  says,  "as 
many  as  eight  hundred  have  been  counted  or  estimated."  In  a 
copious  eruption  in  a  young  boy  we  counted  one  thousand  four 
hundred  lesions;  shortly  afterward  in  an  older  lad  convalescent  from 
scarlatina  we  encountered  a  much  more  extensive  eruption. 
A  photograph  of  this  boy  is  shown  in  Plate  XLII.  We  estimated 
that  there  were  in  the  neighborhood  of  three  thousand  lesions  upon 
the  skin. 

While  neighboring  and  closely  set  vesicles  may  occasionally  coalesce, 
one  never  sees  a  confluence  of  the  lesions  such  as  is  observed  in  smallpox. 

Scarring  After  Varicella. — It  is  not  uncommon  for  some  varicella 
lesions  to  be  followed  by  scars.  Indeed,  it  is  rather  the  rule  for  patients 
to  have  one  or  several  cicatrices  which  persist  after  the  disappearance 
of  the  eruption.  These  are  from  pinhead  to  pea  sized,  rounded  or  oval, 
and  excavated  to  a  variable  degree.  In  severe  cases  the  number  may 
reach  a  half-dozen  or  a  dozen  or  more.  They  are  never,  however,  as 
numerous  as  is  seen  in  smallpox.  The  scars  result  from  a  destruction 
of  the  papillary  layer  of  the  true  skin;  this  may  be  due  to  secondary 
infection  as  a  result  of  scratching,  but  it  may  occur  entirely  apart  from 
this  cause.  Chickenpox  vesicles  at  times  break  down  early  and  produce 
a  necrosis  of  the  underlying  corium;  the  ulcer  left  heals  with  the  form- 
ation of  a  depressed  scar.  Occasionally  a  hypertrophic  scar  or  sort  of 
keloid  forms  at  the  site  of  these  losses  of  tissue. 

The  mucous  membranes  are  not  infrequently  the  seat  of  varicellous 
lesions.  It  is  quite  common  to  find  a  few  vesicles  upon  the  soft  and 
hard  palate,  and  these  in  doubtful  cases  are  of  diagnostic  importance. 
Lesions  are  also  occasionally  noted  upon  the  buccal  mucous  membrane, 
tongue,  and  posterior  pharyngeal  wall.  Situated  in  these  regions  the 
flaccid  roof  of  the  vesicle  soon  ruptures,  leaving  at  first  a  grayish  peUicle 
of  epithelial  debris  and  later  a  circumscribed  superficial  abrasion, 
surrounded  by  a  reddish  areola  and  resembling  to  some  extent  the 
sore  of  aphthous  stomatitis.  The  eruption  in  the  mouth  is  usually  scant, 
even  in  cases  characterized  by  an  abundant  cutaneous  outbreak.  The 
exanthem,  as  a  rule,  appears  synchronously  with  the  eruption  on  the 
skin,  but  it  may  precede  it.  We  know  of  a  colleague  who  was  perplexed 
by  the  appearance  of  a  circumscribed  patch  on  the  posterior  pharyngeal 
wall  of  his  daughter,  but  who  later  discovered  that  it  was  an  early 
varicellous  lesion  preceding  the  general  eruption  by  about  twelve  hours. 

Henoch  has  seen  varicellous  vesicles  on  the  gums  and  also  on  the 
conjunctival  mucous  membrane.  Thomas  observed  the  latter  attacked 
only  when  the  contiguous  portion  of  the  eyelid  was  affected.  He 
likewise  under  similar  conditions  noted  involvement  of  the  nasal 
mucous  membrane. 

Marfan  and  Halle  have  recorded  two  cases  of  involvement  of  the  larynx, 
one  necessitating  tracheotomy.  The  other  case  succumbed  to  other 
complications  and  on  autopsy  the  remains  of  a  vesicle  were  found  on 
the  right  vocal  cord. 


PLATE   XLF. 


An    Unusually  Extensive  Eruption  of  Chiekenpox  in  which  the 
Lesions  -were  Estimated  to  Reach  SOOO  in  number. 


,S'  Y  M I 'TO  MA  TOfAXl  V 


327 


Varicelloiis  lesions  arc  occasionally  found  in  flic;  vc;stil)ule  of  the 
va<);ina  Jind  upon  the  prepuce,  in  wliich  regions  the  accompanying 
swelling  mjiy  cause  difficulty  in  micturition. 

As  far  as  is  known,  chickenpox  never  attacks  the  mucous  membrane 
of  the  slonKich  or  intestines.  Partridge,  in  1SS7,  prcscnicd  to  the  New 
York  l*ii,th()logi(;al  Society  specimens  from  a  child  that  ha<l  died  of 
varicella  complicated  by  bronchopneumonia.  In  the  large  intestines 
were  a  number  of  excoriations  which  were  regarded  as  chickenpox 
lesions. "^  This  child  had  diarrhea  during  life,  and  to  our  minds  it  is 
highly  improbal)lc  that  the  intestinal  lesions  were  of  a  varicellous 
nnturc. 

Varicella  in  Adults. — We  have  preferred  to  consider  chickenpox  in 
the  adult  under  special  heading  in  order  to  give  greater  prominence  to 


Cliickeupox  in  an  adult ;  second  day. 

the  opinion  that  the  frequency  of  this  disease  in  adults  has  been  under- 
estimated. The  assertions  of  many  writers  of  prominence  have  caused 
varicella  in  adult  life  to  be  regarded  as  a  rara  avis.  Thomas,  whose 
teachings  are  based  upon  a  large  and  well-digested  experience,  states: 
"Varicella  is  a  disease  of  childhood,  and  attacks  by  preference  young 
children,  and  even  sucklings.  In  children  over  ten  years  of  age  attacks 
are  infrequent,  and  1 7iever  saw  an  adult  suffering  from  varicella."  And 
again,  "the  predisposition  (to  varicella)  is  wont  to  vanish  of  itself  spon- 
taneously about  the  eleventh  year.""  Von  Jilrgensen^  remarks:  "With 
regard  to  the  differences  between  variola  and  varicella,  it  is  important 
to  state  that  the  latter  is,  if  not  wholly,  yet  practically  limited  to  the 
age  of  childhood^ — the  first  ten  years  of  life;"  and,  further  on,  "Varicella 
is  a  disease  which  is  quite  pecuhar  to  the  age  of  childhood." 


1  Quoted  by  Jeunings.    Keating's  Cyclopedia  of  niseases  of  Children,  p.  761. 

-  Thomas.     Ziemsseu's  Cyclopedia  of  Medicine.    American  edition,  1875,  pp  8  and  27 

3  Nothnagel's  System  of  Medicine.    American  edition,  pp.  288-289. 


328 


CHICKENPOX 


Jonathan  Hutchinson/  in  a  wide  experience,  saw  one  or  two  cases 
about  the  age  of  twenty  and  states  that  "a  point  of  great  interest  in 
varicella  is  the  almost  complete  immunity  of  adults." 

Bohn  encountered  chickenpox  but  once  in  an  adult,  in  a  patient 
aged  sixteen  years,  and  J.  Lewis  Smith  likewise  saw  but  one  case.  Corlett^ 
says:  "During  a  period  of  twenty  years  in  which  the  writer  has  been 
occupied  in  studying  eruptive  disorders,  not  a  single  instance  has 
occurred  in  which  varicella  appeared  after  the  fifteenth  year." 

The  statements  of  these  various  observers  would  lead  one  to  regard 
chickenpox  in  adult  life  as  a  great  rarity.  We  grant  that  adult  varicella 
is  not  an  every-day  occurrence,  but  that  it  is  not  of  excessive  rarity  is 
evidenced  by  the  fact  that  within  eighteen  months  we  have  seen  no 
less  than  16  cases  in  the  city  of  Philadelphia.  During  the  past  thirty- 
two  years  (1870  to  1902)  there  have  been  admitted  into  the  Municipal 
Hospital  35  cases  of  adult  variceUa.  Nearly  all  of  these  cases  were 
sent  into  the  hospital  under  the  erroneous  diagnosis  of  smallpox.  We 
were  enabled  to  successfully  vaccinate  all  those  who  were  not  protected 
by  previous  vaccination. 

In  addition  to  these  35  cases  we  have  seen  5  other  cases  within  the 
past  two  years,  (1901-02)  the  particulars  of  which  we  are  able  to 
recall. 

Table  or  Ages  of  Adult  Cases  of  Varicella. 


Two   were 

.    18  years  old. 

One   was 

.    31  years  old. 

Three     " 

.    19      " 

Three  were 

.    32      ' 

Five 

.     20      " 

" 

.    34      ' 

Two       " 

.     21      '• 

Two  were 

.    35      ' 

<< 

.     21       " 

One  was 

.     36      ' 

Three     " 

.    22      "        " 

Two  were 

.    38      ' 

One  was 

.    23      " 

"       " 

.     39      • 

Three  were 

.    24      " 

One  was 

.    40      ' 

Four       " 

.     25      " 

" 

.     42      ' 

One  was 

.    26      "        " 

"       " 

.    43 

Two  were 

.     27      " 

"       " 

.    48      ' 

One  was 

.     28      " 

Four   were 

.     30      " 

Total  51. 

Of  these  patients  32  were  males  and  19  females;  22  were  negroes  and 
29  were  whites.  We  have  also  seen  a  number  of  cases  of  varicella 
between  the  ages  of  ten  and  eighteen  years,  but  these  have  not  been 
included  in  the  above  table. 

The  history  of  a  patient  admitted  into  the  smallpox  wards  some 
few  months  ago  is  of  interest.  An  unvaccinated  man,  aged  thirty-one 
years,  was  sent  into  the  hospital  with  the  diagnosis  of  smallpox;  he  was 
found  to  be  suffering  from  a  curious  papular  and  purpuric  eruption  of 
undetermined  origin.  He  was  immediately  vaccinated  on  both  arms  and 
on  the  leg.  The  vaccinations  were  all  successful,  but  at  the  end  of 
ten  days  he  fell  ill  and  developed  about  a  half-dozen  variolous  lesions. 
He  was  discharged  from  the  hospital  about  ten  days  later.  About  a 
week  afterward,  he  developed  at  home  a  fairly  extensive  eruption  of 


1  Quoted  by  J.  L.  Smith.    Medical  and  Surgical  Diseases  of  Childhood,  1896,  p.  229. 

2  Infectious  Exanthemata,  Philadelphia,  1901,  p.  165. 


aOMPIJdATIONS  AND  HI'Xid I'lhyK  Oh'  CJ//CKKNPOX  329 

chickenpox.  l(,  was  evident,  tlia.i  this  had  hecn  f;oritrac(e(|  in  the  hfjS[)ital 
from  a  man  sndVu'inff  rrom  varicella  who  was  sent  in  as  a  ease  of  small- 
pox, and  who  was  placed  in  a  sc[)araic  ward  with  the  alK)ve-meritioned 
patient  about  a  week  before  the  latter's  discharge.  It  is  interesting  to 
note  that  tliis  patient  successively  passed  through  attacks  of  cowpox, 
smallpox  (varioloid),  an<l  cliickenj)ox. 

The  underestimated  fre((uency  of  c!iickcn[)ox  in  adnlts  is  further 
attested  by  the  figures  which  Wanklyn'  |)resents  of  the  cases  of  varicella 
sent  to  the  diagnosing  station  of  the  Asylums  JJoard  of  London  during 
the  smallpox  epidemic  of  1901-1902.  Of  200  cases  of  chickenpox 
which  were  seen,  10.7  per  cent.,  or  33  cases,  were  over  eighteen  years 
of  age. 

Lys^  reports  a  family  outbreak  of  chickenpox  attacking  three  sisters, 
all  adults.  On  the  ground  that  chickenpox  was  rare  in  adult  life,  the 
two  sisters  were  permitted  to  associate  with  the  one  originally  attackerl, 
with  the  result  that  they  both  contracted  the  disease. 

There  are  certain  features  of  adult  varicella  which  deserve  mention, 
inasmuch  as  they  are  not  common  in  chickenpox  in  children. 

It  is  not  rare  for  adults  to  feel  ill  a  couple  of  days  before  the  appear- 
ance of  the  varicellous  eruption.  There  may  be  malaise,  chilliness, 
headache  and  some  backache,  nausea  and  moderate  rise  of  temperature 
to  101°  or  102°  F.  These  symptoms  are  similar  to  those  observed  in 
smallpox,  but  are  less  severe.  High  fever,  intense  backache,  repeated 
vomiting,  and  prostration  are  absent  in  chickenpox.  Every  now  and 
then  one  will  see  cases  of  varicella  in  adults  in  which  cjuite  indurated 
papules  will  be  observed  on  certain  parts  of  the  body.  It  is  particularly 
on  the  thick  skin  of  the  forehead  that  these  are  seen.  Typical  vari- 
cellous vesicles,  however,  will  be  found  elsewhere  upon  the  cutaneous 
surface.  A  significant  sign  in  many  of  these  cases  is  the  presence  of 
vesicles  here  and  there  which  have  undergone  rapid  rupture  and  crust- 
ing, with  the  production  of  a  blackish  or  bluish-black  scab  and  depressed  ' 
in  the  centre;  the  borders  of  these  lesions  are  still  vesicular.  They 
present  the  appearance  of  having  been  excoriated  by  scratching. 

COMPLICATIONS  AND  SEQUELS  OF  CHICKENPOX. 

Varicella  is  one  of  the  least  dangerous  of  the  various  exanthematous 
diseases,  both  as  regards  mortality  and  liability  to  complications. 
Nevertheless,  a  sufficient  number  of  rare  complications  has  now  been 
recorded  to  show  that  the  affection  is  not  entirely  devoid  of  danger  to 
life.  Most  of  the  complicating  conditions  result  from  infection  of  the 
skin  at  the  site  of  the  varicellous  vesicles. 

It  is  extremely  common  for  the  partially  dried  vesicle  to  spread  upon 
the  border  in  the  form  of  flat  pustules ;  or  blebs  of  considerable  size  may 
be  formed  which  dry  into  yellowish  friable  crusts.  These  spreading 
pustules  may  attain  the  diameter  of  a  silver  half-dollar.    This  peripheral 

I  British  Medical  Journal,  July  5,  1902.  i  Lancet,  Mav  12,  1SS3. 


330  CHICKENPOX 

extension  is  due  to  infection  of  the  lesion  with  the  pyogenic  organisms 
commonly  found  upon  the  skin,  and  might  appropriately  be  designated 
impetigo  varicellosa.  Most  well-marked  cases  of  chickenpox  show  some 
lesions  which  become  the  seat  of  impetigo.  This  secondary  infection 
is  not  nearly  as  pronounced  as  is  seen  in  smallpox;  in  severe  cases  of 
the  'latter  disease,  an  extensive  impetigo  variolosa  almost  invariably 
occurs. 

Trousseau^  states  that  in  an  epidemic  of  chickenpox  which  prevailed 
in  the  Necker  Hospital  the  fever  ceased  when  the  malady  began,  and 
during  from  fifteen  to  forty  days  pemphigoid  blebs  appeared  on  dif- 
ferent parts  of  the  body,  leaving,  on  the  surfaces  which  they  had  occu- 
pied, ulcerations  exactly  like  those  of  pemphigus,  which  ulcerations 
continued  for  six  weeks  or  two  months. 

The  "sores"  so  frequently  seen  in  chickenpox,  particularly  when  the 
lesions  are  scratched,  represent  impetigo  lesions.  When  these  sores  are 
numerous  a  moderate  elevation  of  temperature  (101°  to  102°  F.) 
may  develop  and  persist  for  several  days. 

As  a  result  of  this  same  infection  the  neighboring  glands  may  become 
enlarged  and,  in  rare  cases,  undergo  suppuration.  Boils  and  sub- 
cutaneous abscesses  may  occur  as  a  result  of  pyogenic  infection.  These 
are  not  infrequently  seen  upon  the  scalp,  although  any  portion  of  the 
cutaneous  surface  may  be  attacked. 

Erysipelas. — Erysipelas  has  been  reported  as  occurring  after  chicken- 
pox.  Freyer^  speaks  of  a  case  of  erysipelas  migrans  complicating 
varicella,  and  Holt^  states  that  he  has  known  of  "three  fatal  cases  of 
chickenpox  resulting  from  erysipelas,  beginning  about  the  pocks." 
When  we  remember  that  erysipelas  is  a  not  uncommon  complication  in 
smallpox,  it  is  not  surprising  that  it  should  occasionally  occur  in  vari- 
cella. 

Pysemia. — A  remarkable  case  of  pyaemia  resulting  from  staphylococcic 
infection  through  the  varicella  lesions  is  reported  by  Brunner.*  The 
child  had  a  suppurative  inflammation  around  the  elbow-joint,  followed 
by  a  double  parotitis  and  abscess  of  the  left  middle  ear,  ending  fatally 
on  the  ninth  day.  Autopsy  disclosed  the  presence  of  pus  in  the  anterior 
mediastinum,  the  pericardium,  the  bronchi,  the  spleen,  and  the  kidneys. 
The  staphylococcus  pyogenes  was  recovered  from  the  blood,  pus,  and 
urine  during  life. 

Lohr  also  records  a  death  from  chickenpox  resulting  from  mixed 
infection  with  the  staphylococcus  pyogenes  aureus. 

Disseminated  Gangrene. — Literature  contains  numerous  references 
to  a  serious  complication  of  chickenpox  which  was  called  by  Hutchinson 
varicella  gangruenosa.  We  have  purposely  avoided  this  name  in  the 
head  line,  inasmuch  as  this  gangrenous  condition  is  not  to  be  regarded 
as  a  variety  of  varicella  or  even  as  a  complication  peculiar  to  this  disease. 
It  may  occur  also  in  vaccinia,  variola,  scarlatina,  typhoid  fever,  and  in 

1  Page  137.  2  Deutsche  med.  Wochenschrift,  1878,  iv.  pp.  111-113. 

i  Loc.  cit. 

4  Quoted  by  Brown.    Article  on  "  Varicella."    Twentieth  Century  Practice  of  Medicine,  1898. 


PLATE  XLIII. 


Impetigo  Varieellosa.     A  pyogenic  condition  analogous   to   but 
milder  than  that  which  develops  about  variolous  pocks. 


COMPLICATIONS  AND  SEQUEL/E  OF  CHICKEN  POX  331 

various  pustular  dermatoses;  it  is  trno,  fiowovcr,  that  it  most  ff>inrnonly 
complicates  varicella.' 

In  mild  cases  but  one  or  several  varicellous  lesions  may  undergo 
necrosis;  in  more  extensive  cases  many  of  the  vesicles  become  involved. 
The  vesicle  may  either  become  converted  into  a  bleb,  the  gangrenous 
process  beginning  beneatli  this  epidermal  elevation,  or  the  vesicle  may 
dry  into  a  dark  crust  and  enlarge  uj)on  th(^  j)eriphcry.  I'pori  removal 
of  the  crust  a  sharply  marginated,  punched-ont,  freely  discliarging  ulcer 
is  seen.  A  dusky-red  areola  surrounds  the  ulcer  or  eschar.  In  extensive 
cases  the  temperature  rises  to  104°  or  105°  F.,  and  the  patient  rapidly 
sinks.  ■  Ivung  complications,  particularly  pulmonary  infarction,  are 
common.  Mild  cases  of  gangrene  may  recover.  The  affection  is 
most  common  in  debilitated  infants,  more  especially  those  in  whom 
the  varicella  is  preceded  by  some  other  illness.  In  Griffith's  case  the 
chickenpox  was  preceded  by  measles,  diphtheria,  and  pneumonia. 

Cases  of  gangrenous  varicella  have  been  reported  by  Hutchinson, 
Demme,  Abercrombie,  Andrew,  Crocker,  Biichler,  Jamieson,  Lowen- 
hardt,  Payne,  Stanifooth,  Haward,  Vierordt,  Griffith,  Lockwood,  Silver, 
Woodward,  and  others. 

We  have,  on  several  occasions,  observed  localized  gangrene  occurring 
at  the  site  of  smallpox  pustules;  these  cases  all  terminated  fatally. 
Stokes,^  of  Dublin,  reports  a  case  of  vaccinia  gangrenosa  ending  in 
recovery. 

Synovitis  and  Arthritis. — Synovitis  and  arthritis  have  been  reported 
as  rare  complications.  Laudon^  and  Ferret'  have  both  published 
examples  of  joint  involvement  in  chickenpox.  The  patient  of  the 
former,  a  boy  aged  four  years,  developed  high  fever  early  in  the  course 
of  varicella,  followed  by  marked  swelling  of  the  left  elbow-joint.  Re- 
covery took  place  after  several  weeks. 

Semtschenke,  quoted  by  Rille,  saw  2  cases  of  purulent  pleurisy  and 
purulent  arthritis  in  an  epidemic  of  chickenpox  in  Russia. 

Hogyes  reports  a  case  of  varicella  in  a  seven-year-old  girl  followed 
by  nephritis  and  subsequently  by  an  inflammation  of  several  joints, 
accompanied  by  high  fever  and  ending  in  recovery. 

Braquehaye  saw  a  purulent  arthritis  of  the  knee  and  elbow  develop 
on  the  ninth  day  of  a  varicella  which  w^as  apparently  running  a  normal 
course.  Despite  incision  and  drainage  death  resulted.  On  autopsy  a 
septic  endocarditis  was  also  discovered.^ 

Marfan  and  Halle"  describe  2  cases  of  serous  involvement  of  the  larynx 
through  the  presence  of  varicellous  vesicles.  In  one  case,  in  a  boy  of 
three  years,  tracheotomy  was  performed,  the  patient  recovering.  In  the 
other,  a  child  of  nine  months,  with  a  well-marked  chickenpox,  developed 

1  An  excellent  description  of  this  afiection  is  given  by  Crocker  under  the  title  o."  "Dermatitis 
Gangrsenosa  Infantum."    Text-book  of  Diseases  of  the  Skin.    American  edition,  1903,  p.  535. 
-  Dublin  Journal  of  Medical  Sciences,  June,  ISSO. 
^  Deutsche  med.  Wochenschrift,  Leipzig,  1890,  xvi.  p.  5G7. 
*  Province  mt>d.  Lyon,  1SS9,  iii.  pp.  256-261. 
6  Quoted  by  Brown.    Twentieth  Century  Practice  of  Medicine. 
6  Quoted  by  Brown.    Ibid. 


332  CHICKENPOX 

stridor  and  dyspnoea;  diphtheria  bacilli  were  absent.  Bronchopneu- 
monia and  diarrhoea  supervened  and  death  resulted;  the  post-mortem 
examination  revealed  the  presence  on  the  right  vocal  cord  of  a  round, 
shallow  ulcer,  evidently  the  remains  of  a  varicella  vesicle. 

Nephritis. — Nephritis  is  one  of  the  most  serious  of  the  complications 
and  sequelse  of  varicella.  While  it  occurs  in  only  a  very  minute  per- 
centage of  cases,  there  are  in  the  literature  a  sufficient  number  of  recorded 
instances  to  cause  physicians  to  keep  in  mind  the  possibility  of  its 
development  and  to  watch  the  kidneys  in  the  treatment  of  this  otherwise 
trivial  disease. 

Henoch^  was  one  of  the  first  to  mention  nephritis  as  a  complication 
and  reported  4  cases  following  chickenpox.  Janssen,^  Hogyes,^  Oppen- 
heim,*  Brunner,^  Unger,®  Rille,^  Schwab,  von  Jiirgensen^  and  Dillon 
Brown''  have  all  described  similar  cases. 

The  nephritis  usually  comes  on  during  the  first  or  second  week 
of  the  disease.  It  varies  in  severity  as  does  this  complication  in  other 
infectious  diseases.  In  severe  cases  an  abundance  of  albumin  and 
tube  casts  may  be  present  in  the  urine.  As  a  rule,  the  nephritis  is 
mild,  recovery  taking  place  promptly.  Dillon  Brown,  however,  reports 
a  case  in  which  the  kidney  involvement  after  a  mild  attack  of  varicella 
ran  a  chronic  course,  ending  fatally  some  ten  years  later.  Ildgyes' 
case  terminated  fatally  through  complication  with  pneumonia,  and 
Rille  reports  an  uncomplicated  nephritis  ending  in  death  and  showing 
on  autopsy  parenchymatous  changes  in  the  kidneys. 

Bronchitis  and  Bronchopneumonia. — Bronchitis  and  bronchopneu- 
monia are  mentioned  as  complications  by  Meigs  and  Pepper,  and  Rille 
reports  a  peculiar  form  of  pleuropneumonia  ending  fatally  on  the 
nineteenth  day  after  varicella. 

Association  of  Chickenpox  with  Other  Exanthematous  Diseases. — 
It  is  not  at  all  uncommon  for  varicella  to  develop  during  convalescence 
from  other  acute  exanthematous  diseases,  such  as  measles,  scarlet  fever, 
smallpox,  etc.  On  the  other  hand,  these  diseases  may  develop  in 
patients  suffering  from  varicella.  It  is  rather  rare  for  these  eruptive 
diseases  to  be  synchronously  present  in  their  acutest  stages;  usually  the 
second  disease  appears  as  the  first  is  beginning  to  decline. 

Chickenpox  has  repeatedly  broken  out  in  the  diphtheria  and  scarlet- 
fever  wards  of  the  Municipal  Hospital.  Under  these  circumstances  the 
varicella  would  naturally  appear  not  earlier  than  the  end  of  the  second 
week  of  the  original  disease.  We  have  often  seen  varicella  appear  in 
scarlet-fever  patients  who  were  profusely  desquamating.  We  have  also 
observed  these  two  diseases  present  at  the  same  time  with  vaccinia. 

1  Berliner  klin.  Wochenschrift,  No.  2,  January,  1884.  -  Nedre.  Tijdsch.,  1884,  B.  xx.  p.  223. 

3  Orvosi  hetil.,  Budapest,  1885,  xxix.  pp.  11-16. 
*  Berliner  klin.  Wochenschrift,  December  26,  1887. 

5  Aerztl.  Mitth.  a-Baden,  Karls  nute,  1888,  xlii.  pp.  49-52. 

6  Wien.  med.  Presse,  1888,  xxix.  pp.  1449-1451. 

7  Wien.  klin.  Woch.,  1889  ;  Deutsche  med.  Woch.,  1891. 

8  Nothnagel's  Encyclopedia  of  Medicine.    Article  on  "  Varicella." 

9  Twentieth  Century  Practice  of  Medicine.    Article  on  "  Varicella." 


(]()MI'IJ(!.\TI()NH  AND  Sf'Xjff I'JL.f:  OF  ('II K' K ICS I'OX  ,'},'J.^j 

Chickenpox  may  af)|)ciir  diiiiiif;-  coiivalcsccnfc  from  smjillprjx.  'I'lif 
foll()win<i;  oulhroak  of  cliickciijx^x  nmon^  lliirty-llircc;  cliildr-cii  con- 
valescent from  smallpox  is  of  iiilcrcsl: 

In  November,  1900,  a  child  suffering  from  chickenpox  was  sent 
into  the  Municipal  Hospital  of  Pliiladclpliia,  under  the  erroneous 
dia<i;nosis  of  smallpox.  The  true  character  of  the  disease  was  recoj:(nized 
and  the  child  vaccinated.  This  patient  did  not  cfmtract  smallpox, 
but  succeeded  in  transmitting  varicella  to  a  number  of  other  children 
in  the  ward.  These  in  turn  infected  new  patients  as  they  arrived,  and 
in  this  manner  varicella  i'emained  in  the  children's  ward  for  a  period 
of  three  months.  In  all,  thirty-three  children  suiferinj;^  from  smallpox 
were  attacked.  It  should  be  stated  that  a  much  larger  number  ol 
children  escaped  infection.  Whether  this  was  due  to  temporary  insus- 
ceptibility or  to  their  having  previously  had  chickenpox,  it  is  impossible 
to  say.  The  attacks  were  in  the  main  mild  and  the  accompanying 
eruption  moderate  in  extent.  Inasmuch  as  the  patients  were  exjjosed 
during  the  eruptive  period  of  smallpox,  the  chickenpox  eruption  did  not 
appear  until  after  the  variolous  lesions  had  become  crusted  or  were 
disappearing.  The  earliest  onset  of  varicella  was  in  a  girl,  aged  seven 
years,  who  developed  chickenpox  on  the  seventeenth  day  of  the  variolous 
outbreak.  In  this  patient  the  firm,  compact,  crusted  lesions  of  smallpox 
appeared  in  strange  contrast  with  the  recent  dewdrop-like  vesicles  of 
chickenpox.  The  patient's  temperature  had  not  yet  reached  normal, 
but  was  hovering  about  100°  F.  at  the  time  of  the  appearance  of 
the  chickenpox  eruption.  It  then  rose  to  102°  F.,  subsiding  rapidly  to 
100°  F.,  and  in  a  few  days  again  rising  to  103°  F.  owing  to  the  develop- 
ment of  an  abscess.  In  this  child  the  two  diseases  may  be  said  to 
have  existed  simultaneously. 

The  chickenpox  efflorescence  appeared  in  most  of  the  patients  from 
the  twentieth  to  the  thirty-fifth  days  of  their  smallpox  eruption.  As 
the  majority  of  these  children  entered  the  hospital  on  the  third  or 
fourth  day  of  the  variolous  eruption,  it  is  seen  that  many  of  the  patients 
did  not  contract  chickenpox  for  about  a  month  after  they  were  exposed. 
Inasmuch  as  the  period  of  incubation  of  varicella  is  about  fourteen  to 
eighteen  days,  seldom  longer  than  three  weeks,  this  observation  would 
suggest  that  during  the  early  eruptive  period  of  smallpox  many  of  the 
children  were  not  susceptible  to  the  infection  of  chickenpox.  To 
generalize,  we  should  say  that  most  of  the  little  patients  received  the 
infection  of  varicella  during  the  desiccative  stage  of  smallpox  or  at 
about  the  end  of  two  weeks  of  the  smallpox  eruption. 

Smallpox  and  chickenpox  may  actually  exist  at  the  same  time.  Trous- 
seau states  that  Delpech  published  a  paper  in  1S45  in  which  he  reported 
the  simultaneous  presence  in  a  child  of  the  eruptions  of  chickenpox  and 
smallpox.  We  have  seen  one  such  case  ourselves,  the  attendant  circum- 
stances of  which  leave  no  doubt  as  to  the  correctness  of  the  diagnosis. 

Coincident  Smallpox  and  Chickenpox. — S.  F.,agirl  aged  fiveyears, 
developed  an  eruptive  disease  which  was  regarded  by  a  physician  as 
suspicious;  thereupon  two  other  physicians  independently  visited  the 


334  CHICKENPOX 

patient  and  pronounced  the  disease  to  be  chickenpox.  The  lesions 
dried  up  in  the  usual  time,  but  two  weeks  later  the  girl  became  ill  and 
developed  typical  smallpox.  It  is  undesirable  to  publish  the  circum- 
stances, but  the  fact  is  established  that  the  variolous  infection  was 
carried  to  the  child's  home  at  one  of  the  visits  above  referred  to. 

Thirteen  days  after  the  above  patient  was  first  seen,  a  smaller  sister, 
aged  two  years,  developed  the  eruption  of  chickenpox.  Twenty-four 
hours  later  the  characteristic  lesions  of  smallpox  appeared  upon  her. 
It  is  to  be  noted  that  this  child  was  exposed  to  the  smallpox  infection 
at  the  same  time  as  her  sister.  On  admission  to  the  hospital  the  little 
patient  was  covered  with  firm  variolous  papules.  The  face,  arms,  and 
legs  were  profusely  involved,  the  trunk  to  a  lesser  extent.  Upon  the 
forehead  near  the  border  of  the  hair  were  two  crusted  and  superficially 
ulcerated  varicella  lesions.  A  half-dozen  or  more  varicellous  lesions  were 
also  observed  upon  the  back  and  a  few  on  the  abdomen  and  chest.  Upon 
the  lower  portion  of  the  back  was  a  comparatively  recent  chickenpox 
vesicle  just  beginning  to  dry.  The  subsequent  course  of  the  case  left 
no  doubt  as  to  the  variolous  nature  of  the  second  eruption.  Two  other 
children  of  this  family  who  were  protected  against  smallpox  by  previous 
vaccination  showed  crusted  varicellous  lesions  upon  different  portions 
of  the  body. 

THE   PATHOLOGY  OF  CHICKENPOX. 

The  Skin. — Unna  excised  a  characteristic  "chickenpox"  lesion  from 
an  eight-year-old  boy  on  the  second  day  of  its  existence.  The  following 
description  is  condensed  from  Unna's  detailed  findings; 

In  contrast  with  the  central  depression  in  the  variolous  vesicle  the 
vesicle  of  varicella  is  tent-shaped,  with  the  central  point  at  the  summit. 
The  lateral  walls  rise  obliquely  from  a  broad  base  toward  the  roof, 
which  is  formed  by  a  few  stretched,  horny  scales.  From  these  cellular 
partitions  radiate  downward  as  in  smallpox.  The  chickenpox  lesion 
is  consequently  divided  like  the  smallpox  lesion,  but  the  point  where 
the  septa  join  lies  not  in  the  centre  of  the  base,  but  in  the  covering  or 
roof.  The  cavity  proper  only  occupies  the  upper  part  of  the  much- 
widened  prickle  layer.  It  is  limited  beneath  by  the  deeper  strata  of 
the  prickle  layer,  which  show  pathological  changes.  In  the  centre  the 
cavity  extends  downward  to  the  papillae  of  the  corium,  which  are  swollen 
and  enlarged  and  which  project  into  the  cavity.  The  roof  of  the  vesicle 
is  formed  by  the  original  horny  layer  with  the  addition  of  a  few  layers 
of  flattened  transitional  epithelium. 

The  degenerative  changes  in  the  cells  of  the  rete  mucosum  are  typically 
represented  in  varicella  and  can  be  better  studied  in  this  disease  than 
in  variola,  for  in  the  latter  affection  the  onset  of  suppuration  obscures 
the  process.  The  early  pus  formation  and  the  slowness  of  the  process 
are  the  chief  features  which  distinguish  the  cavity  formation  in  small- 
pox from  that  in  chickenpox.  Extensive  fibrinoid  metamor'phosis  of 
the  epithelium  takes  place  as  in  variola.  The  varicellous  process 
commences  with  the  reticulating  liquefaction  of  a  few  prickle  cells   of 


tup:  DIAO'NOSfS  OF  CfffCK/'JNPOX  337 

of  premonitory  .symptoms  should  always  he  reganled  as  a  matter  of 
great  diiTcreiitial  importance. 

Except  for  occasional  malaise  a  half-day  or  so  before  the  appearance 
of  the  chickenpox  eruption  there  is,  in  the  vast  majority  of  cases,  no 
prodromal  stage.  We  have  recently  had  the  opportunity  in  the  Municipal 
Hospital  of  studying  an  outbreak  of  chickenpox  among  convalescents 
from  scarlet  fever.  The  continuous  temperature  records  show  that  in 
nearly  every  case  the  eruption  appeared  before  any  pyrexial  elevation 
occurred.  Occasionally  in  adults,  chickenpox  may,  however,  be  pre- 
ceded by  a  prodromal  illness  suggestive  of  but  milder  than  that  observed 
in  smallpox.  These  patients  seldom  experience  vomiting  or  prostration, 
and  the  febrile  elevation  is,  as  a  rule,  moderate. 

3.  Constitutional  Symptoms. — The  fever  and  prostration  in  the 
eruptive  stage  are  usually  more  severe  in  smallpox  than  in  chickenpox. 
This  is  not  an  invariable  guide,  however,  as  severe  cases  of  varicella  are 
accompanied  by  higher  temperature  than  very  mild  cases  of  smallpox. 

4.  Distribution  of  the  Eruption. — It  is  a  well-known  and  important 
fact  that  the  smallpox  eruption  attacks  with  predilection  the  face  and 
distal  portions  of  the  extremities.  Upon  the  trunk,  and  especially  the 
abdomen,  the  lesions  are  nearly  always  more  sparse.  In  chickenpox 
the  eruption  is  usually  most  profuse  on  the  trunk,  particularly  the  back, 
and  relatively  sparse  on  the  wrists,  hands,  feet,  and  face.  In  general, 
it  may  be  stated  that  smallpox  prefers  the  exposed  surfaces  and  chicken- 
pox  the  covered. 

It  has  been  stated  that  chickenpox  does  not  attack  the  palmar  and 
plantar  surfaces.  This  statement  is  erroneous,  inasmuch  as  the  palms 
of  the  hands  and  soles  of  the  feet  are  every  now  and  then  attacked  in 
pronounced  cases.  Of  course,  one  never  sees  such  a  profusion  of  lesions 
in  these  regions  as  is  observed  in  smallpox. 

5.  Extent  of  the  Eruption. — The  number  of  lesions  upon  the  skin 
should  not  be  regarded  as  important  evidence.  An  unvaccinated  child 
admitted  some  months  ago  into  the  Municipal  Hospital  had  but  five 
lesions  upon  the  entire  cutaneous  surface.  On  the  other  hand,  a  lad 
with  chickenpox  occupying  a  different  ward  had  about  1400  lesions  and 
another  boy  over  3000. 

6.  Character  of  the  Lesions. — In  smallpox  the  eruption  begins  as 
firm  papules,  which  slowly  increase  in  size  and  develop  into  vesicles 
and  pustules.  Not  all  variolous  papules  are  shotty,  but  they  are  more 
deeply  seated  and  have  a  more  infiltrated  base  than  the  chickenpox 
lesions.  The  variolous  vesicles  are  often  harder  than  the  papules. 
They  are  moderately  uniform  in  size,  and  are  often,  although  by  no 
means  always,  umbilicated.  The  vesicles  are  multilocular  and  difficult 
to  rupture  with  the  finger-nail. 

Chickenpox  lesions  may  begin  as  maculopapules,  but  within  a  few 
hours  some  become  frankly  vesicular.  The  epidermal  roof  is  thin  and 
easily  broken,  permitting  the  exit  of  a  clear,  watery  serum.  "With  the 
collapse  of  the  vesicle  the  infiltration  seems  to  disappear  and  a  super- 
ficial   excoriation   is    often  left.      The  vesicle  is  often  unilocular,  but 


338  ^  CHICKENPOX 

little  diagnostic  value  should  be  placed  upon  the  comparative  degree 
of  evacuation  of  variolous  and  varicellous  vesicles  with  a  needle. 
Chickenpox  lesions  vary  greatly  in  size,  some  being  as  small  as  a  millet 
seed  and  others  as  large  as  a  finger-nail.  They  do  not  become  umbili- 
cated  save  by  central  caving  in  or  desiccation.  The  early  drying,  with 
the  production  of  a  depressed,  blackish  crust  in  the  centre  and  irregular 
puckering  of  the  vesicle  or  pustule  on  the  periphery,  is  highly  character- 
istic of  chickenpox. 

It  is  not  rare  in  an  extensive  eruption  of  varicella  to  find  one  or  several 
vesicles  which  resemble  variolous  vesicles,  and,  on  the  other  hand,  in 
smallpox  to  occasionally  see  a  few  superficial  vesicles  which  resemble 
those  of  chickenpox. 

7.  Manner  of  Eruption. — The  eruption  of  smallpox  comes  out  with- 
out interruption  in  the  course  of  twenty-four  to  forty-eight  hours.  The 
lesions  show,  therefore,  a  quite  uniform  development.  (It  should  be 
remarked,  however,  that  the  eruption  on  the  face  is  always  a  little  in 
advance  of  the  development  elsewhere.)  The  chickenpox  eruption 
comes  out  in  crops  on  successive  or  alternate  days,  and  the  lesions  may 
be  seen  in  varying  stages  of  development.  The  coexistence  of  recent 
tense  vesicles,  older  puckered  vesicopustules,  and  dried  crusts  is  highly 
characteristic  of  the  disease. 

8.  Course  of  the  Eruption. — Smallpox  lesions  undergo  a  gradual  evolu- 
tion from  papule  to  crust  in  the  course  of  ten  to  twelve  days  (in 
modified  cases  five  to  six  days).  Chickenpox  lesions  last  from  two  to 
four  days  and  then  crust.  The  crusts  of  smallpox  are  dense  and  compact, 
while  those  of  chickenpox  are  thin  and  friable.  The  presence  of  numer- 
ous hard,  mahogany-colored  crusts  embedded  in  the  horny  layer  of  the 
palms  and  soles  bespeaks  smallpox. 

There  is  no  one  characteristic  symptom  on  which  a  differential 
diagnosis  between  smallpox  and  chickenpox  can  be  based.  The  case  is 
to  be  viewed  in  all  its  aspects  and  a  diagnosis  made  from  the  history 
and  the  associated  local  and  constitutional  manifestations.  A  due 
sense  of  proportion  should  be  exercised  in  attributing  proper  weight  to 
the  presence  and  absence  of  the  various  symptoms.  Even  when  this  is 
done  there  are  occasional  cases  in  which  twenty-four  hours'  delay  and 
observation  are  desirable  in  order  to  definitely  establish  the  diagnosis. 

Impetigo  Contagiosa.^ — If  chickenpox  is  seen  after  the  desiccation 
of  the  vesicles  the  disease  may  be  confounded  with  impetigo.  Indeed, 
impetigo  is  commonly  engrafted  upon  a  varicella,  in  which  event  the 
lesions  spread  upon  the  borders  in  the  form  of  a  vesicular  ring.  Impetigo 
contagiosa  is  characterized  by  the  formation  of  vesicles  or  blebs  which 
rapidly  become  pustular,  rupture,  and  form  superficial  crusts.  The 
face  is  the  seat  of  predilection  and  is  usually  exclusively  affected,  although 
the  hands,  and  in  rare  cases  the  trunk,  may  present  lesions.  The 
vesicles  are  thin-roofed  and  flaccid,  seldom  exhibiting  the  tenseness  of 
varicella  vesicles.  The  patient,  as  a  rule,  suffers  no  constitutional 
disturbance  at  all.  The  mucous  membrane  of  the  mouth  is  exempted. 
The  lesions  do  not  appear,  as  in  varicella,  in  several  crops,  but  increase 


Till':  riiOdNOHJH  AND  TRI<:ATM MNT  OF  dll [(!K FN I'OX  339 

irregularly  as  a  result  of  finger  inoculation.    The  disease  is  caused  by 
inoculation  of  the  skin  with  certain  pyogenic  organisms. 

Varicella  runs  a  briefer  course  and  tiie  lesions  disappear  in  a  short 
time  without  local  treatment;  the  existen(;e  of  antecerlent  cases  of 
chicken[)ox,  or  the  development  of  later  ones,  after  an  interval  of  two 
weeks  constitutes  strong  corroborative  evidence. 

THE  PROGNOSIS   AND   TREATMENT  OF   CHICKENPOX. 

Prognosis. — Chickenpox  is,  with  the  possible  exception  of  riibella, 
the  mildest  of  the  acute  exanthematous  diseases.  As  Trousseau  remarks, 
patients  never  die  of  varicella  fer  se,  although  deaths  in  rare  instances 
have  occurred  from  complications.  Most  of  the  complications  which 
have  been  recorded  have  been  wound  infections — impetigo,  erysipelas, 
al)scesses,  gangrene,  etc.  With  the  exception  of  the  first-named  con- 
dition, these  are  extremely  rare.  Varicella  may  at  times  induce  an 
anaemia  or  general  failure  of  health  which  may  predispose  to  tuber- 
culosis. 

Treatment.^ — When  chickenpox  appears  in  a  househokl  it  is  scarcely 
necessary  to  isolate  the  patient.  Varicella  is  such  a  mild  disease  that 
it  is  just  a  question  whether  children  in  good  health  should  not  be 
allowed  to  take  it.  Those  who  reach  adult  life  without  passing  through 
the  disease  are  apt  to  contract  it  at  times  under  awkward  and  embarrass- 
ing circumstances.  When  children  are  weakly  or  suffering  from  some 
other  disease,  they  should,  if  possible,  be  protected  against  chickenpox. 
W^hen  isolation  is  carried  out  it  should  be  continued  until  detachment 
of  all  of  the  primary  crusts. 

The  constitutional  symptoms  of  varicella  are  ordinarily  so  m  Id  as 
to  require  no  internal  treatment.  Where  there  is  febrile  disturbance 
children  should  be  kept  in  bed  and  upon  a  bland  diet. 

The  local  treatment  is  of  considerable  importance.  When  the  vesicles 
become  distended  with  pus,  particularly  those  on  the  face,  they  should 
be  evacuated  and  cleansed  with  a  weak  antiseptic  solution.  The 
following  ointment  will  be  found  useful  in  preventing  secondary  infection 
of  the  lesions: 

{V— Acidi  carboliei gr.  x. 

Hydrargyri  chlorid.  mit gr.  xv. 

I'Lilv.  aniyli, 

Pulv.  zinci  osidi ad  5ij. 

Petrolati Sss. 

As  has  already  been  stated,  some  chickenpox  lesions  are  followed  by 
indelible  scars;  these  may  be  due  to  an  early  necrosis  involving  the 
papillary  layer  of  the  skin,  in  which  event  they  cannot  be  prevented. 
In  other  cases  the  scars  are  due  to  a  slow  ulceration  the  result  of  pyogenic 
infection  of  the  lesions.  Scratching  is  liable  to  produce  scars  by  infect- 
ing the  skin.  In  young  children  the  finger-nails  should  be  closely 
trimmed  to  prevent  traumatism  from  scratching;  when  scratching 
cannot  be  otherwise  controlled  the  hands  should  be  enclosed  in  muslin 


340  CHICKENPOX 

bags  attached  firmly  about  the  wrists.  Doubtless  the  rare  cases  of 
varicella  gangraenosa  are  due  to  infection  of  the  skin.  It  is  important 
to  keep  the  hands  and  the  entire  body  scrupulously  clean. 

To  relieve  the  tching  which  is  not  infrequently  present,  the  following 
lotion  will  be  found  efficacious: 

Jfc— Acidi  carbolici gr.  xxx.  to  Sj. 

Glycerini 5j. 

Spts.  vini  recti •       .  fSss. 

Aquee q.  s.  ad  fSvj. — M. 

S. — Use  locally. 

In  severe  cases  it  is  important  to  examine  the  urine  to  be  sure  that 
a  nephritis  be  not  present.  If  the  latter  complication  arises  it  should 
be  treated  upon  the  usual  principles  governing  the  care  of  this  condition. 


CHAPTER    YII. 

SCART.ET  FEVER. 

Synonyms. — Scarlatina:  Gcnnaii,  IScliarlacJi;  French,  la  Scarlatine; 
Italian,  Scarlattina;  Spanish,  escarlatina;  I^atin,  febris  rubra. 

Definition. — Scarlatina  is  an  acute,  specific,  infectious  disease,  char- 
acterized by  a  sudden  onset  with  high  fever,  headache,  vomiting,  and 
sore  throat,  followed  on  the  second  day  by  a  generalized  punctiform 
rash  which  later  gives  rise  to  desquamation. 

There  is  a  tendency  to  the  development  of  cervical  abscess,  otitis 
media,  and  nephritis.  One  attack  usually  confers  immunity  for  a 
life-time. 

History. — The  origin  of  scarlet  fever  is  involved  in  obscurity;  there 
are  many  suggestive  descriptions  in  the  writings  of  the  later  Greek  and 
Roman  physicians,  but  none  are  sufficiently  complete  and  explicit  to 
warrant  the  conclusion  that  they  referred  to  scarlet  fever.^  ]Malfatti^ 
regarded  the  terrible  epidemic  (the  pest  of  Thucydides)  that  swept 
Athens  in  429  e.g.  as  scarlatina,  but  it  is  evident  from  a  study  of  the 
symptoms  of  this  malady  that  there  is  no  adequate  reason  for  such  a 
view;  indeed,  angina  was  the  only  symptom  that  this  pest  had  in 
common  with  scarlatina. 

Some  writers  have  believed  that  certain  passages  in  the  works  of 
Hippocrates  referred  to  scarlatina,  but  inasmuch  as  no  mention  was 
made  by  this  careful  observer  of  the  most  conspicuous  spnptom  of 
this  disease,  namely,  the  exanthem,  it  may  be  accepted  that  the  refer- 
ences in  question  pertained  to  another  malady  (in  all  probability  diph- 
theria). Rhazes^  stated  that  measles  of  vivid  coloration  was  more 
dangerous  than  that  which  was  but  moderately  red.  Rhazes  may 
have  seen  scarlatina,  but  it  is  useless  conjecture  to  construe  such  sentences 
as  the  one  just  mentioned  as  references  to  scarlatina. 

Gregory^  says  that  scarlet  fever  "probably  invaded  the  world  soon 
after  measles  and  smallpox  made  their  debut,  for  the  Arabian  physicians 
describe  a  species  of  measles  which,  from  the  extent  of  the  desquama- 
tion, we  may  be  assured  was  scarlatina." 

Not  until  the  sixteenth  century  is  reached  do  we  find  convincing 
descriptions  of  scarlet  fever.  Ingrassias,  of  Palermo  (1560),  depicted 
this  disease  and  was  the  first  to  properly  differentiate  it  from  measles. 

He  also  called  attention  to  the  fact  that  the  disease  attacked  an 

1  For  much  of  the  history  herein  coutained  we  are  indebted  to  the  painstaking  work  of  Xoirot, 
Histoire  de  la  scarlatine,  Paris,  1847. 
-  Hufeland's  Journal  der  pract.  Heilkunde,  Bd.  xii.,  St.  3,  p.  120. 
3  Cont.  lib.  xviii.,  cap.  8,  f.  328,  d.  383.  ■•  Eruptive  Fevers,  New  York,  1S51,  p.  1-16. 


342  SCARLET  FEVER 

individual  but  once,  and  that  children  were  the  most  frequent  subjects, 
but  that  adults  were  not  invariably  spared. 

In  1574  Baillou  described  under  the  name  of  ruhiolw.  an  epidemic 
malady  which  was  prevailing  in  Paris;  this  disease  he  carefully  differ- 
entiated from  measles  (morhilli). 

Jean  Coyttar,^  of  Poitiers,  in  1578,  described  the  features  of  an 
epidemic  which  differed  both  from  smallpox  and  from  measles,  and 
which  was  strongly  suggestive  of  scarlatina. 

In  1610  an  epidemic  angina  accompanied  by  a  scarlet  eruption  is 
said  to  have  raged  in  Spain,  and  to  have  passed  thence  to  Naples,  which 
was  at  that  time  under  Spanish  control.  Ludovic  Mercatus,  in  1612, 
and  Michael  Heredia,  in  1626,  fully  and  clearly  described  these  anginose 
cases.  Sgambatus,  an  Italian  physician  wrote,  in  1620,  of  "de  pestilente 
faucium  affectu  neapoli  saeviente,"  and  his  fellow-countryman,  Oetius 
Clerus,  described  "de  morbe  strangulatorio"  in  1636. 

Daniel  Sennert,^  of  Wittemberg,  in  the  first  half  of  the  seventeenth 
century  (about  1625),  described  the  disease  scarlet  fever  as  we  see  it 
at  the  present  day.  The  rash,  the  desquamation  from  the  seventh  to 
the  ninth  day,  and  joint  pains  are  all  carefully  and  faithfully  depicted. 
This  is,  perhaps,  the  earliest  reference  in  literature  which  may  be 
credited  as  pointing  unmistakably  to  scarlatina.  Sennert's  son-in-law, 
Doering,  saw  a  similar  epidemic  in  Poland;  he  called  attention  to  the 
occurrence  of  delirium,  anasarca,  and  rheumatoid  pains. 

We  are  indebted  to  Sydenham  (born  1624  and  died  1689)  for  the 
name  scarlatina  or  scarlet  fever,  and  for  the  crystallization  of  the  medical 
comprehension  of  this  morbid  process.  It  is  claimed  by  Corradi  that 
the  designation  "mala  da  scarlatina"  was  employed  in  1527  by  Lance- 
lotti,  but  Hirsh  believes  the  term  was  not  applied  to  the  disease  later 
described  under  the  name  of  scarlet  fever.  Sydenham's  experience  was 
evidently  limited  to  normal  and  mild  forms  of  the  disease;  he  did  not 
encounter  the  severe  anginose  forms  which  were  shortly  afterward 
(in  1698)  referred  to  by  Morton.  The  latter  writer,  however,  obscured 
the  concept  of  the  disease  by  asserting  his  belief  that  scarlatina  was 
a  confluent  form  of  measles.  This  erroneous  conception  has  from  time 
to  time  been  revived  at  different  epochs  of  the  nineteenth  century. 

Diemerbroeck,  the  Dutch  physician,  in  1640,  wrote  of  a  disease  under 
the  title  of  purpura,  which  he  believed  to  be  a  variety  of  measles,  but 
which,  according  to  Gregory,  was  obviously  scarlet  fever. 

In  1665  an  epidemic  of  scarlatina  occurring  in  Poland  was  described 
by  Schultz  under  the  name  of  purpura  epidemica  maligna;  the  title 
suggests  that  the  disease  prevailed  in  virulent  form.^    Toward  the  end 

1  Thaerei  Alsiniensis,  cons,  et  m^d.  regis,  "de  febre  purpura  epidermiale  et  contagiosa,  libri  duo," 
Parisiis,  .1578. 

2  Opera  Omnia,  tome  vi.,  lib.  5,  cap.  12,  p.  183. 

3  Scarlatina  was  first  observed  in  Hungary  by  Rayger  ;  in  Leipzig,  by  Ettmiiller  and  Lange  ;  in 
Modena,  by  Ramazzini,  and  in  Augsburg,  by  Schroeck.  It  appeared  in  Scotland  toward  the  end  of 
the  seventeenth  century,  for  Sir  Robert  Sibbald,  physician  to  the  Court  of  Charles  II.,  said,  in  1694, 
that  the  disease  had  so  recently  appeared  in  the  kingdom  that  he  would  not  hazard  an  opinion 
upon  it. 


scAii/j<;T  i<i<:vh:ii  84.3 

of  the  eighteenth  century  and  in  (Ik;  early  |);irt,  f)f  IIk;  ninc-Uir-ntli,  sr-arla- 
tina  seerneil  to  accjuire  an  augmented  rn;dign;iney.  Tlie  inereased 
frecjueney  and  severity  of  scarlatin.'i,  in  the  hegirming  of  the  nineteenth 
century  was  speciously  attributed  hy  (xrundniann,  P'unk,  and  otiiers 
to  the  introduction  of  vaccination.  Noirot  pertinently  remarks  that 
vaccination  has  influenced  the  occurrence  of  scarlatina  l^y  delivering 
up  to  it  and  to  other  diseases  of  infancy  nniltitudes  of  infants  who 
without  vaccination  would  have  been  destined  to  succumh  to  smallf>ox 
at  an  early  age. 

During  the  eighteenth  century  epidemics  of  scarlatina  were  observed 
in  all  parts  of  Europe. 

A  severe  epidemic  of  scarlatina  prevailed  in  Lon<lon  in  1747-48, 
This  was  described  by  Fothergill  (then  a  young  man  entering  the 
profession)  under  the  title  of  "an  account  of  the  sore  throat  attended 
with  ulcers,  a  disease  which  hath  of  late  years  appeared  in  this  city, 
and  in  several  parts  of  the  nation."  He  had  the  clearness  of  vision  to 
recognize  that  the  disease  was  due  to  "the  reception  into  the  habit  of 
a  putrid  virus  or  miasm,  sui  generis  by  contagion,  and  principally  by 
means  of  the  breath."  The  disease  was  for  a  long  time  referred  to 
as  Fothergill's  sore  throat. 

The  same  epidemic  extended  to  Plymouth,  where,  in  17.5],  it  was 
carefully  studied  and  reported  by  Huxham.  In  1799  Withering  pub- 
Ushed  an  account  of  an  epidemic  which  was  raging  in  Birmingham. 
He  at  first  drew  distinctions  between  the  scarlatina  anginosa  of  the 
older  authors  and  Fothergill's  sore  throat,  but  later  acknowledged  that 
from  an  assiduous  study  of  the  disease  for  fifteen  years  he  was  con- 
vinced that  they  were  one  and  the  same  disease. 

In  France  an  extensive  epidemic  occurred  in  1750.  The  following 
French  physicians  of  the  eighteenth  century  left  important  writings  on 
scarlatina:  Navier  Lorry,  Dupuy  de  la  Porcherie,  Sauvage,  and  De- 
sessarts.  The  disease  was  studied  during  this  era  in  Germany  by 
Storch  and  Plenciz;  in  Holland  by  de  Haen,  Keetell,  and  Bicker;  in 
Italy  by  Parolini,  Targioni,  and  Ghisi,  and  in  Scotland  by  Brodly  and 
Coventry. 

Scarlatina  first  appeared  in  the  United  States,  according  to  Thomas, 
in  1735.  It  is  quite  probable  that  the  disease  prevailed  among  the 
colonists  from  time  to  time  in  the  pre-revolutionary  period,  although 
only  after  the  American  Revolution  of  1776  did  mention  of  scarlatina 
appear  in  medical  literature.  The  first  monograph  on  the  subject 
published  in  this  country  was  by  Dr.  Israel  Allen;  it  was  entitled  A 
Treatise  on  the  Searlatina  Anginosa,  Leominster,  Massachusetts,  1796. 

According  to  Dr.  Joseph  M.  Toner^  scarlatina  appeared  in  Boston 
in  1702  and  again  in  1735;  in  Kingston,  Mass.,  in  1735;  in  Philadelphia 
in  1746,  and  in  Connecticut  in  1751.  The  disease  became  pandemic 
in  1790  and  again  in  1830.  Scarlatina  first  made  its  appearance  in 
Iceland  in  1827,  and  in  Greenland  in  1847. 

>  Quoted  by  Thomas  C.  Minor,  in  a  report  to  the  American  Public  Health  Association,  1875. 


344  SCARLET  FEVER 

ETIOLOGY. 

Despite  the  fact  that  the  causative  agent  of  scarlet  fever  has  not 
yet  been  discovered,  the  statement  may  be  made  that  the  disease  is 
produced  by  a  specific  micro-organism.  Scarlet  fever  is  so  similar 
in  its  behavior  and  manner  of  transmission  to  other  infectious  diseases 
of  proven  parasitic  origin  that,  reasoning  by  analogy,  we  are  irresistibly 
forced  to  this  conclusion.  Not  many  years  ago  it  was  maintained  by 
writers  that  cases  of  scarlet  fever  could  arise  de  novo,  independently 
of  pre-existing  cases.  The  spontaneous  origin  of  infectious  diseases  is 
no  longer  credited  by  medical  scientists  of  the  present  day.  The  channels 
of  infection  are  often  so  devious  and  the  manner  of  transmission  so 
mysterious  as  to  make  the  origin  of  these  diseases  in  individual  instances 
quite  incomprehensible.  But  the  mystery  of  an  infection  is  dispelled 
and  becomes  as  clear  as  the  trick  of  the  magician  when  the  solution  is  at 
hand.  The  proposition  may,  therefore,  be  accepted  that  every  case  of 
scarlet  fever  has  its  origin  in  an  antecedent  attack  in  another  individual. 

Modes  of  Transmission  of  the  Scarlatina  Contagium.— The  germ 
of  scarlet  fever  is  chiefly  if  not  exclusively  conveyed  in  two  ways:  (1) 
directly  from  a  scarlatina  patient  to  the  newly  infected  subject,  and 
(2)  through  the  intermediation  of  infected  objects. 

The  vast  majority  of  cases  of  scarlatina  doubtless  result  from  exposure 
to  persons  suffering  from  the  disease;  this  is  freely  admitted.  A  certain 
school  of  German  writers,  led  by  von  Kerchensteiner,  maintains  that 
the  disease  cannot  be  conveyed  hy  a  third  person.  The  clinical  experience 
of  numerous  careful  observers  is  strongly  opposed  to  such  an  opinion. 
Indeed,  there  are  recorded  instances  of  such  transmission  which  appear 
quite  conclusive. 

Dr.  Loeb,  of  Worms,  mentions  the  case  of  his  three-year-old  daughter 
who  developed  scarlet  fever  at  a  time  when  there  were  no  known  cases 
in  the  city.  The  origin  of  the  infection  was  a  mystery  until  it  was 
discovered  that  a  medical  friend  and  colleague  who  had  been  at  the 
house,  and  upon  whose  lap  the  little  girl  had  sat  for  a  long  time,  had 
some  hours  previously  visited  three  cases  of  severe  scarlatina  in  another 
city  and  had  not  changed  his  clothes.  The  disease  manifested  itself 
at  the  end  of  two  days.  The  circumstances  surrounding  the  case  would 
seem  to  point  in  the  strongest  manner  possible  to  the  conveyance  of 
the  germs  in  the  clothes  of  the  physician. 

Thomas  saw  a  case  "in  which  a  nurse  coming  directly  from  a  scar- 
latinous patient  communicated  the  disease  in  the  short  space  of  three 
hours  to  a  child  who  had  almost  recovered  from  a  tracheotomy."  He 
also  quotes  Zengerle  to  the  effect  that  a  healthy  woman,  after  a  visit 
to  a  scarlatinous  patient,  transmitted  the  disease  to  her  daughter,  who 
was  the  first  patient  affected  in  the  whole  city.  Murchison  was  con- 
vinced, from  the  testimony  he  had  received  from  numerous  physicians, 
that  the  scarlet-fever  infection  was  not  rarely  carried  by  them. 

The  infection  commonly  clings  to  objects  which  have  come  in  contact 
with  the  scarlet-fever  patient,  such  as  bedding,  clothing,  books,  letters, 


ETIOLOGY  345 

toys,  etc.  Numerous  instances  are  recorded  in  which  such  articles 
have  transmitted  the  infection.  IJotli  Tiic-htirdson  and  Peterson  traced 
cases  of  scarlet  fever  to  infection  transjnilled  in  letters.  It  is  an  important 
matter  in  infectious-disease  hospitals  that  all  outgoing  mail  lie  thor- 
oughly disinfected. 

The  scarlet-fever  contagium  may  cling  tenaciously  and  for  a  long  time 
to  the  sick-room  and  to  certain  objects  contained  therein.  Murchison, 
on  the  testimony  of  Richardson,  mentions  an  extremely  sad  illustration 
of  this.  A  child  having  been  seized  with  a  fatal  attack  of  scarlet  fever 
in  a  country  house,  the  three  remaining  children  were  fjuickly  removed. 
After  a  lapse  of  several  weeks  one  child  that  was  brought  home  con- 
tracted in  twenty-four  hours  an  attack  of  scarlet  fever  to  which  he 
rapidly  succumbed.  The  house  was  then  thoroughly  cleaned  and  the 
walls  whitewashed,  but  the  infection  was  not  removed,  for  a  third  child 
that  returned  after  four  months  took  the  disease  and  died  in  the  same 
manner  as  the  others.  It  is  believed  that  the  infection  was  retained 
in  a  thick  layer  of  straw  covering  on  the  children's  beds. 

Von  Hildebrand  claims  to  have  contracted  the  disease  from  a  black 
coat  which  he  had  worn  a  year  and  a  half  before  while  attending  a  case 
of  scarlet  fever  in  Vienna. 

The  most  remarkable  claim  of  longevity  of  the  scarlet- fever  infection 
is  mentioned  by  Boeck  (quoted  by  Johannessen,  loc.  cif.),  who  relates  the 
circumstance  as  follows: 

"The  children  of  a  colleague  of  mine  had  obtained  permission  to  play 
with  some  things  in  an  old  writing  desk.  In  a  drawer  lay  some  hair  that 
had  been  cut  from  two  children  that  had  died  of  scarlet  fever  tiventy 
years  before;  since  that  time  the  drawer  had  not  been  touched.  Now 
it  was  opened  and  the  children  took  scarlatina.  These  cases  were  the 
first  in  the  city,  so  that  the  probability  is  evident  that  the  infection 
was  transmitted  in  this  way." 

Immunity  and  Susceptibility.— There  is  no  such  universal  suscept- 
ibility of  persons  to  scarlet  fever  as  is  known  to  exist  toward  measles 
and  smallpox.  Experience  teaches  that  but  few  people  enjoy  a  natural 
immunity  against  these  latter  diseases.  Many  persons,  however,  escape 
contracting  scarlet  fever  even  though  freely  exposed  to  its  infection. 

The  contagion  of  scarlet  fever  is  a  most  ca'pricious  one;  it  may  repeat- 
edly spare  an  exposed  individual  and  lead  him  to  believe  that  he  is 
immune  against  it,  only  to  smite  him  at  some  subsequent  period. 

This  temporary  immunity  against  scarlet  fever  has  been  repeatedly 
noted  by  various  observers.  Nurses  have  frequently  been  observed 
during  the  closest  attendance  upon  patients  suffering  from  scarlet  fever 
to  remain  free  from  infection,  and  yet  later  contract  the  disease.  Such 
a  case  has  recently  come  under  our  observation: 

Mrs.  X.,  aged  thirty  years,  a  private  trained  nurse,  was  brought  into 
the  Municipal  Hospital  on  January  9,  1903,  suffering  from  a  well- 
pronounced  attack  of  scarlet  fever.  She  had  never  had  the  disease  in 
childhood.  During  the  past  few  years  she  estimated  that  she  had  nursed 
about  fifteen  cases  of  the  disease.     On  November  17,  1902,  she  com- 


346  SCARLET  FEVER 

pleted  her  service  in  connection  with  a  severe  case  of  scarlet  fever  in  the 
suburbs  of  Philadelphia.  A  little  over  six  weeks  later  she  began  to 
nurse  a  patient  with  puerperal  scarlet  fever.  After  being  on  duty  four 
days  she  herself  was  taken  with  a  scarlatina  of  average  severity,  which 
ran  a  typical  course  and  was  followed  by  profuse  desquamation. 

We  recall  the  case  of  an  ambulance  driver  at  the  Municipal  Hospital 
who  came  in  almost  daily  contact  with  cases  of  scarlet  fever,  and  who 
finally  at  the  end  of  several  years  contracted  a  well  pronounced  attack 
of  the  disease. 

On  another  occasion  one  of  the  nurses  at  the  Municipal  Hospital 
contracted  a  well  marked  attack  of  scarlatina  on  returning  to  duty  in 
the  scarlet-fever  wards  after  a  year's  absence.  Prior  to  her  departure 
she  had  nursed  mixed  cases  of  diphtheria  and  scarlatina  for  a  period  of 
three  months. 

It  would  appear  in  these  cases  that  for  some  reason  or  other  the 
resisting  power  of  the  subject  is  lowered  at  the  time  of  infection;  this 
explanation  seems  to  us  to  be  more  plausible  than  the  assumption  that 
the  attack  is  determined  by  an  unusually  intense  infective  agent. 

In  some  instances  it  would  appear  that  the  temporary  immunity 
against  scarlet  fever  is  overcome  by  infection  through  unusual  channels. 
The  puerperal  state  and  surgical  operations  are  said  to  favor  the  develop- 
ment of  the  disease. 

Von  Leube^  gives  an  interesting  account  of  an  attack  of  scarlatina  in 
his  own  person  following  a  wound  received  in  making  an  autopsy  upon 
a  patient  who  had  died  of  an  unusually  severe  case  of  scarlet  fever. 
He  states  that  he  had  considered  himself  perfectly  immune,  having  been 
exposed  as  a  child,  and  having  attended  any  number  of  cases  under  all 
sorts  of  circumstances.  Ten  days  after  the  post-mortem  wound  upon  his 
finger  he  developed  sore  throat,  and  on  the  following  day  he  vomited, 
had  a  "decided  fever,"  and  the  scarlatina  rash.  The  course  of  the  disease 
was  one  of  medium  severity. 

The  susceptibility  to  scarlatina  commonly  disappears  in  adult  life; 
at  any  rate,  many  adults  who  have  never  had  the  disease  escape  infection, 
although  freely  exposed.  Patients  suffering  from  scarlet  fever  have  on 
numerous  occasions  been  placed  in  the  wards  of  general  hospitals 
without  appearing  to  disseminate  the  disease  among  other  occupants 
of  the  ward.  Such  experiences  illustrate  the  very  limited  suscepti- 
bility of  persons  who  have  passed  the  age  of  puberty. 

During  the  past  few  years  the  students  of  the  various  medical  colleges 
in  Philadelphia  have  been  conducted  through  the  wards  of  the  Municipal 
Hospital  in  order  to  study  the  various  infectious  diseases  therein  treated. 
About  700  students  in  all  have  taken  advantage  of  this  bedside  instruc- 
tion. They  were  taken  into  the  scarlet-fever  wards  in  which  there  were 
100  or  more  cases  of  this  disease,  and  remained  from  one  to  two  hours 
in  this  intensely  infected  atmosphere.  About  one-half  of  these  students, 
according  to  their  statements,  had  never  had  scarlet  fever,  and  yet  not  a 

1  Specielle  Diagnose  der  inneren  Krankheiten,  Bd.  ii.  p.  364.    Leipzig,  1893. 


ETIOLOGY  347 

single  one  contracted  the  disease.  Tliis  is  strong  proof  of  (lir;  frequent 
ahrf)gation  of  the  siisc<>|)lil)iliiy  of  adults  to  scarlet  f(!ver. 

Epidemics  Among  Adults. — VogI,'  of  the  (j(;rieral  Medical  Staff  of 
Bavaria,  reports  two  epidemics  of  scarlet  fever  among  the  Bavarian 
troops  at  Munich.  In  1884-S5,  during  a  garrison  epidemic  covering  a 
period  of  ITSdays,  125  out  of  7442  soldiers,  or  1.07  per  cent.,  contracted 
the  disease.  The  mortality  rate  was  4  per  cent.  In  1804-95,  during  a 
similar  epidemic  lasting  155  days,  311  out  of  OfiOS  troops,  or  3.23  per 
cent.,  took  scarlatina,  of  whom  1.2  per  cent,  dierl.  The  attack  rate 
among  exposed  adults  is  thus  seen  to  be  very  small. 

Murchison  estimated  that  the  number  of  persons  attacked  with 
scarlet  fever  in  England  and  Wales  was  considerably  less  than  one-half 
of  the  number  of  l)irths.  It  is  evident,  therefore,  that  the  lessened 
susceptibility  to  scarlatina  exhibited  in  adult  life  is  not  entirely  due  to 
protection  granted  by  an  attack  in  childhood. 

This  is  also  shown  by  the  figures  of  scarlatina  in  virgin  countries. 
From  1873  to  1875  an  extensive  epidemic^  of  scarlatina  raged  in  the 
Faroe  Islands.  The  disease  had  not  been  known  in  this  locality  for 
fifty-seven  years  and  possibly  had  never  occurred  at  all.  From  the 
carefully  collected  data  of  Hoff  concerning  the  town  of  Thorshavn,  the 
chief  city  of  the  islands,  it  is  seen  that  of  a  population  of  930  persons, 
237  contracted  the  disease.  Among  the  entire  inhabitants  of  the  islands, 
of  whom  none  had  ever  had  scarlatina,  but  38.3  per  cent,  contracted 
the  disease  during  this  protracted  epidemic. 

Age. — Age  is  a  most  pronounced  factor  in  the  determination  of 
susceptibility  to  scarlet  fever.  It  is  a  general  experience  that  infants 
under  one  year  of  age  exhibit  a  lessened  disposition  to  contract  the 
disease;  this  is  still  more  true  of  nurselings  under  six  months,  and  in 
infants  under  three  months  of  age  scarlatina  is  excessively  rare.  The 
infrequency  of  the  disease  at  this  tender  age  may  be  judged  by  the 
statements  of  experienced  observers  in  reference  thereto. 

Fleischmann^  saw  no  cases  under  six  months  of  age;  Eulenberg,  none 
under  eight;  Thomas,  none  under  five;  Boning  saw  no  cases  under  one 
year;  Senfft  saw  but  one  patient  under  one  year,  and  Gaupp  only  two. 
Haller  observed  a  case  at  five  months;  Voit,  one  at  two  and  a  half 
months;  Kiipfer,  one  at  two  months;  and  Veit,  one  at  two  weeks. 

This  represents  an  extremely  scant  number  w^hen  the  large  number 
of  cases  of  scarlatina  observed  by  these  men  is  taken  into  consideration. 
In  Johannesen's  statistics  of  scarlet  fever  deaths  in  Norway  from  1862 
to  1878,  the  number  of  infantile  attacks  is  considerably  greater.  He 
reports  15  deaths  from  scarlatina  under  six  months,  and  93  under  one 
year.  In  our  own  experience  at  the  Muincipal  Hospital  we  have  found 
that  among  5000  cases  of  scarlet  fever  admitted  into  the  hospital,  about 
1  per  cent,  consisted  of  infants  under  one  year  of  age.  We  have  on  a 
number  of   occasions  had  infants  a  few  months  old  brought  into  the 

1  Miinchener  med.  Wocli.,  1895,  p.  949. 

-  Mentioned  by  von  Jurgensen  in  Nothnagel's  Encyclopedia  of  Practical  Medicine. 

3  Mentioned  by  Thomas  in  Ziemssen's  Encyclopedia  of  Practice  of  Medicine,  p.  180. 


348  ^  SCARLET  FEVER 

hospital  with  mothers  suffering  from  scarlatina,  but  we  have  seldom 
observed  them  to  contract  the  disease.  We  have  seen  them  suckle  at 
breasts  covered  with  the  scarlatinal  rash,  draw  a  febrile  milk,  and  yet 
remain  perfectly  well. 

The  question  whether  there  is  a  congenital  scarlatina  is  most  difficult 
to  answer.  Children  are  so  commonly  ushered  into  the  world  with  a 
red  rash  that  but  little  reliance  can  be  placed  upon  the  existence  of  an 
exanthem.  Furthermore,  it  is  not  uncommon  for  the  tender  epidermis 
of  the  infant  to  peel  off  after  some  days  and  thus  cause  a  desquamation. 
Baillou,  Ferrario,  Stiebel,  Hiiter,  and  others  saw  infants  that  were 
alleged  to  have  scarlatina  at  birth  (most  of  them  being  born  of  mothers 
suffering  from  scarlet  fever  at  the  time),  but  the  facts  do  not  appear  to 
us  to  warrant  the  unreserved  acceptance  of  the  diagnosis.  Murchison 
saw  two  pregnant  women  with  scarlet  fever,  and  in  each  case  the  child 
born  at  the  time  was  free  of  the  disease.  Elsasser  also  saw  a  healthy 
babe  born  of  a  mother  with  scarlatina. 

Children  from  two  to  five  years  of  age  appear  to  be  most  susceptible 
to  the  contagium  of  scarlatina.  From  five  to  ten  years  the  attack  rate 
is  somewhat  less,  and  after  the  period  of  puberty  is  reached  the  suscept- 
ibility to  the  disease  is  greatly  lessened.  No  age,  however,  appears  to 
guarantee  absolute  immunity  against  scarlatina  inasmuch  as  persons 
even  over  the  age  of  ninety-five  have  been  known  to  contract  the  dis- 
ease. 

Murchison's  valuable  statistics  of  scarlet-fever  deaths  in  England  and 
Wales,  covering  the  enormous  number  of  148,829,  will  give  a  fairly 
accurate  idea  of  the  incidence  of  the  disease  in  the  different  age  periods : 

Under    1  year 9,999  or  6.7  per  ct. 

From      1  to   2  years 20,975  "  14.1 

2  "     3  " .  23,842  "  16.0 

3  "    4  " 22,528  "  15.1 

4  "     6  " 17,726  "  11.9 

5  "  10  " 38,591  "  25.9 

"        10  "  15  " 8,676  "  5.8 

Total  under    5  years 95,070   or    63.8  per  ct. 

From  5  to  15  years 47,267 

15  "  25  " ,  .  3,871 

"        25  "  35  " 1,306 

35  "  45  "        .        . 671 

"        45  "  55  " 331 

55  "  65  " 185 

"        65  "  75  " 88 

"        75  "  85  " 30 

"        85  "  95  " 4 

Over  95  "        .        ; 6 


Total 148,829 

It  will  be  seen  from  the  above  tables  that  considerably  over  one-half 
of  the  deaths  of  scarlatina  occurred  in  children  under  five  years  of  age. 
Almost  90  per  cent,  occurred  in  those  under  ten  years,  and  over  95  per 
cent,  under  fifteen  years  of  age. 

These  figures  correspond  very  closely  with  statistics  of  scarlet-fever 
deaths  in  Berlin  from  1875  to  1891,  and  with  Johannesen's  statistics  for 


ETIOLOGY  :W.) 

Norway.     As  showing  the  fatal  cases  in  cliildrcii.iKKler  ouc  yrar,  the 
latter  statistics  are  of  particular  interest : 

Fatal  Cases  of  Scarlatina  in  CuRisTrANA  (Jndkk  Onk  Ykarch    Af;K, 

(JOHANNESEN.) 

iBt  month 0 

2(1     to       3d  month .'{ 

4th    "      f)th        " 12 

7th    "    12th        " 78 

The  above  deaths  were  out  of  a  total  of  1040  fatal  cases. 

Family  Predisposition. — Some  families,  at  times,  exhibit  an  unusual 
susceptibility  to  scarlatina;  this  is  manifested  not  only  by  several  mem- 
bers of  the  family  contracting  the  disease,  but  likewise  by  the  severity 
of  the  attack.  Thomas^  recognizes  "an  intense  family  predisposition, 
showing  itself  by  numerous  and  severe  attacks  in  the  family  as  soon  as 
one  infection  has  taken  place  in  it."  Trousseau  says:  "Scarlatina 
epidemics  may  be  full  of  danger  for  an  entire  population,  or  they  may 
assume  this  character  only  for  a  single  family.  The  malignancy  limits 
itself  in  a  measure  to  a  single  hearth,  and  in  such  cases  the  disease  is 
malignant  for  all  persons  that  live  within  its  circle."  Henoch^  expresses 
much  the  same  idea;  he  says:  "Striking  to  me  appeared  the  fact  that  if 
scarlatina  breaks  out  in  a  family,  very  frequently  also  a  second  and  third 
child  are  taken  off  under  similar  conditions,  and  in  this  way  whole 
families  can  die  out." 

Copeman,^  during  a  severe  epidemic  of  scarlet  fever  in  1844,  saw  four 
children  in  a  family  die  so  suddenly  that  poisoning  was  suspected ;  a  fifth 
child  went  through  an  ordinary  attack  of  scarlet  fever. 

A  somewhat  similar  instance  has  recently  come  under  our  observation. 
In  the  winter  of  1902  we  saw  a  family  in  which  four  children  were 
smitten  with  scarlet  fever.  All  fell  suddenly  ill  with  vomiting,  which 
was  attributed  by  the  mother  to  free  indulgence  in  candy.  Soon  the 
scarlatinal  rash  manifested  itself.  The  eldest  daughter,  a  girl  of  seven- 
teen, died  in  five  days;  a  second  one  had  a  temperature  of  105°  F., 
with  intense  prostration,  and  recovered,  as  did  a  third  child,  only  after 
a  most  desperate  illness.  The  infection  in  these  cases  was  most  viru- 
lent, and  yet  the  prevailing  type  of  scarlatina  in  the  city  at  that  time 
was  quite  mild. 

These  severe  family  epidemics  are  difiicult  to  account  for.  Henoch 
presupposes  a  mixed  infection  in  such  cases.  Thomas  does  not  seek 
an  explanation  in  an  unusually  intense  infection,  for  he  says  "the 
infecting  cases  are  frequently  of  a  mild  character." 

Epidemics  of  this  character  are  happily  uncommon.  In  some  instances 
there  is  a  tendency  to  family  immunity,  the  members  thereof  exliibiting 
an  almost  complete  insusceptibility  to  the  disease. 

Climate. — Accordingto  INIinor,^  who  has  in  a  most  painstaking  manner 
studied  the  prevalence  of  scarlatina  in  the  United  States,  climatic  con- 
ditions influence  the  spread  of  the  disease.    He  says: 

1  Loc.  cit,  p.  175.  -  Vorlesungen  iiber  Kinderkrankheiten,  p.  654.  third  edition. 

3  Jahresbericht,  etc.,  der  Gesammteu  Medicin.     E.  Virchow  and  A\\%.  Hirsch,  vi.  Jahrgang,  1S71, 
vol.  ii.  p.  247.  4  Loc.  cit.,  p.  13. 


350  <  SCARLET  FEVER 

1.  "The  zone  of  comparative  immunity  in  the  Eastern  Hemisphere 
extends  from  10°  south  latitude  to  20°  north  latitude."  (In  this  zone 
are  found  Sumatra,  Borneo,  India,  and  most  of  Africa.) 

2.  "A  zone  of  comparative  immunity  in  the  Western  Hemisphere 
extends  from  the  equator  to  10°  north  latitude."  (In  this  zone  are 
found  Venezuela-  and  the  States  of  Colombia.) 

3.  "Another  zone  of  comparative  immunity  in  the  Western  Hemisphere 
extends  from  30°  to  35°  north  latitude."  (In  this  zone  are  found  South 
Carolina,  Georgia,  Alabama,  Mississippi,  Louisiana,  Texas,  and  the 
northern  part  of  Florida.)  According  to  the  vital  statistics  of  the  United 
States  for  the  year  1900  these  States,  with  the  exception  of  Texas,  had  a 
remarkably  small  scarlatina  mortality  compared  with  other  sections  of 
the  country. 

4.  "In  times  of  pandemics,  occasional  epidemics  occur  at  points 
within  the  zones  of  comparative  immunity."  The  disease  in  these 
regions,  however,  attacks  by  preference  the  Caucasian  race. 

Minor  furthermore  says  that  in  these  countries,  "lying  for  the  most 
part  in  the  tropics  and  near  the  equator,  exposed  to  the  direct  rays  of 
the  sun,  a  high  mean  annual  temperature  is  of  course  noticeable." 
This  author,  after  discussing  the  climatic  influences,  concludes  that 
"a  very  high  temperature,  combined  with  periodical  humid  atmos- 
phere, is  unfavorable  to  the  development  of  any  scarlatinous  ten- 
dency." 

Season. — Hirsch  has  studied  the  seasonal  incidence  of  435  epidemics 
of  scarlet  fever  occurring  in  Norway,  Sweden,  Russia,  Germany, 
Holland,  France,  Italy,  Spain,  and  North  America.  Most  of  the  epi- 
demics occurred  in  autumn,  as  will  be  seen  from  the  following  figures: 
autumn,  29.5  per  cent.;  winter,  24.7  per  cent.;  summer,  24  percent., 
and  spring,  21.8  per  cent. 

In  England,  since  the  days  of  Sydenham,  it  has  been  recognized  that 
scarlatina  prevails  most  in  the  fall;  55,956  deaths  in  London  from 
scarlatina  during  a  period  of  twenty-four  years  gave  the  following 
percentages:  autumn,  35.54  per  cent.;  winter,  23.85  per  cent.;  summer, 
22.75  per  cent.;  spring,  17.87  per  cent. 

In  the  United  States  scarlatina  is  most  prevalent  during  the  latter 
part  of  winter  and  during  the  ea^'ly  spring  months.  The  vital  statistics 
for  1870  show  the  largest  number  of  deaths  in  March.  The  first  five 
months  of  the  year  exhibit  a  considerably  greater  mortality  than  the 
rest  of  the  year: 

Scarlatina  Deaths  by  Months  in  the  United  States  in  1870. 


January 

.     2205 

February 

.    2393 

March 

.    2726 

April  . 

.     2294 

May    . 
June   . 
July    . 

.     2146 
.    1826 
.     1216 

August 

.    1096 

September 

.      927 

October     . . 

.    1000 

November 

.     1281 

December  . 

.     1705 

Unknown  . 

5 

Total    .        .        .  20,320 


I'lTIOUXlY 


351 


Arranged  according  to  seasons,  (Ik^  figures  read  as  follows: 


Spring 
Summor 


710(1 
3038 


Aiilnrnii 
Winder 


.",208 
0303 


Tlie- vital  statisfics  of  the  United  States  for  the  year  1000,  although 
somewliat  ditrerently  j)resented  with  reference  to  scarlet-fever  mortality, 
give  similar  results: 

Scarlatina   Deatuk   by  Months  i-ek  1000  of   Deaths   from  Ali,  (Jaijsrs 
IN  THE  United  States  in  1900. 


January    . 

.    118.3 

AugUHt 

50.3 

February  . 

.    112.8 

September 

52.5 

March 

.    1008 

October     . 

69.4 

April 

.    105.7 

November 

84.8 

May    . 

.      98.4 

December . 

98.7 

June  . 

.      50.0 



July  .        .       . 

.      40.3 

Total  actual  deaths 

6333 

Here  again  it  is  seen  that  the  greatest  mortality  from  scarlet  fever 
is  in  the  late  winter  and  early  spring  months. 

According  to  Murchison,  epidemics  of  scarlet  fever  in  France  occur 
more  frequently  in  the  spring  and  summer  months. 

Johannesen  classifies  as  follows  65,785  cases  of  scarlet  fever  occurring 
in  Sweden  from  LSGT  to  1878: 


January 

February 

March     . 

April 

May 

June 


11.3  per  ct. 
9.2 
9.1 


6.9 


July    . 

August 

September 

October 

November 

December 


6.6  per  ct. 

0.3 

5.7 

8.0 
10.4 
10.7 


It  is  seen  that  the  greatest  number  of  cases  occurred  in  November, 
December,  and  January. 

In  Berlin,  from  1877  to  1883,  there  were  5428  deaths  from  scarlatina, 
with  the  following  monthly  mortality: 


January   . 

.    6.7 

per  ct. 

July    . 

.      8.0  per  ct 

February 

.    5.3 

August 

.      8.5 

March 

.     .5.8 

September 

.    10.7 

April 

.     6.1 

October      . 

.    13.8 

May  .        .        . 

.     7.0 

November 

.     10.9 

June 

.     8.1 

December 

.      8.5        " 

The  greatest  number  of  deaths  occurred  in  autumn — September, 
October,  and  November,  the  maximum  being  reached  in  October. 

From  the  various  statistics  presented  it  is  seen  that  season  apparently 
has  some  influence  on  scarlatina  prevalence.  The  same  months  in 
different  countries  show,  however,  Avidely  divergent  figures. 

The  different  character  of  the  climate  in  the  countries  mentioned  may 
account  for  the  discrepancies  in  the  monthly  morbidity  incidence.  It 
will  be  necessary  to  carefully  compare  the  climatic  and  meteorological 
conditions  by  month  in  the  various  countries  before  an^-thing  can  be 
definitely  said  as  to  the  influence  of  season  upon  the  spread  of  scarlatina. 

Minor^  studied  the  influence  of  temperature  on  the  prevalence  of 


1  Loc.  cit..  p.  51. 


352  SCARLET  FEVER 

scarlatina  and  came  to  the  conclusion  that  the  colder  weather  seemed 
to  favor  the  scarlatinous  tendency.     He  states  that: 

1.  The  scarlatinous  tendency  is  but  slightly,  if  at  all,  modified  by  a 
temperature  ranging  from  zero  to  65°  F. 

2.  The  scarlatinous  tendency  is  decidedly  modified  and  lessened 
by  a  temperature  ranging  from  75°  to  80  °  F. 

3.  The  scarlatinous  tendency  is  almost  entirely  destroyed  where  there 
is  a  prolonged  high  temperature  ranging  from  80°  to  85°  F. 

Influence  of  Urban  and  Rural  Localities. — As  would  be  naturally 
expected,  the  prevalence  of  scarlatina  is  greater  in  city  than  in  country 
districts.  This  is  to  be  accounted  for  by  the  more  extensive  intercourse 
between  cities  and  by  the  greater  crowding  and  more  intimate  contact 
of  the  people.  The  vital  statistics  of  the  United  States  for  the  year 
1900  show  a  very  distinct  difference  between  the  city  and  rural  death  rate 
by  months: 

Death  Rate  from  Scarlatina  by  Months  in  Cities  and  Rural  Districts, 
PER  1000  OF  All  Deaths. 

Cities.  Rural. 

January 1.6  0.8 

February 1.8  0.9 

March 1.5  0.9 

April 1.4  0.8 

May 1.4  0.7 

June 1.0  0.4 

July 0.6  0.3 

August 0.5  0.3 

September 0.4  0.3 

October 0.8  0.4 

November 0.8  0.8 

December 1.2  0.8 

Scarlet  fever  is  practically  endemic  in  the  great  centres  of  civilization ; 
the  disease  in  the  large  cities  of  the  world  increases  and  decreases  from 
time  to  time,  but  never  dies  out  completely. 

Altitude. — Minor^  says  in  regard  to  altitude  that  "  scarlatina  prevails 
at  all  altitudes,  epidemics  occurring  at  New  York,  Providence,  and  Bos- 
ton, on  the  Atlantic  coast;  at  Pittsburg,  Cincinnati,  Chicago,  Detroit,  and 
St.  Louis,  in  the  interior  of  the  continent;  finally,  among  the  mountains 
of  Nevada,  and  at  San  Francisco  on  the  Pacific  slope.  In  order  to 
determine  whether  altitude  seems  to  modify  or  lessen  the  tendency  to 
scarlatina,  we  shall  group  the  States  as  follows:  First  group.  States 
having  average  altitudes  ranging  from  150  to  600  feet,  are  Tennessee, 
Vermont,  Kentucky,  Georgia,  North  Carolina,  Texas,  Massachusetts, 
Maine,  Maryland,  Alabama,  South  Carolina,  Arkansas,  Connecticut, 
Mississippi,  New  Jersey,  Rhode  Island,  Delaware,  Louisiana,  and 
Florida.  Total  population  of  this  group,  in  1870,  was  14,597,384. 
Second  group,  States  having  average  altitudes  ranging  from  600  to  1000 
feet:  Iowa,  Wisconsin,  Missouri,  Michigan,  New  York,  Pennsylvania, 
Ohio,  Virginia,  Indiana,  Illinois,  and  New  Hampshire.    Total  population 

1  Loc.  cit.,  p.  54. 


i<'/ri()[/)GY  353 

of  this  grou|),  In  IS70,  was  21,500,509.  Thirrl  group,  States  having 
average  altitudes  ranging  from  1000  to  5400  feet:  Nevada,  California, 
Oregon,  Nebraska,  Kansas,  Minnesota,  and  West  Virginia.  'J'otal 
population  of  this  group,  in  1.S70,  was  2,i:i3,:j]6.  In  these  three  groups 
of  States,  20,15!)  deaths  from  scarlatina  occurred — i.  e.,  3833  in  th(!  first, 
15,351  in  the  second,  and  1475  in  the  third.  If  we  analyze  these 
figures,  the  following  is  the  result: 

Altitude.  JJcaths. 

150    to     600  feet 1  death  to  every  4380  of  population. 

600      "     1000    " 1      ..       »      u      1401  "  " 

1000      "     5400     " 1      ' 1447  "  " 

"  NoviT,  taking  into  consideration  the  density  of  population  in  the 
second  group  as  compared  with  the  third,  together  with  the  fact  that 
scarlatina,  being  a  contagious  disease,  should  be  more  prevalent  where 
it  has  the  largest  and  densest  population  to  prey  upon,  we  conclude 
that  altitude  rather  favors  an  increase  of  the  scarlatinous  tendency." 

A  striking  difference  in  the  prevalence  of  scarlatina  in  certain  of  the 
European  capitals  has  been  observed.  In  London,^  from  1868  to  1872, 
there  were  nearly  115,000  cases  of  scarlet  fever.  In  Berlin,  from  1877 
to  1883,  scarlatina  caused  5428  deaths.  On  the  other  hand,  during  a 
period  of  five  years  in  Paris,  the  total  deaths  from  scarlet  fever  were 
only  67. 

It  is  quite  inexplicable  why  London  and  Berlin  should  suffer  so 
severely  from  this  disease  while  Paris  possesses  a  comparative  immunity. 

Race. — There  is  strong  evidence  that  negroes  are  less  susceptible  to 
scarlet  fever  than  the  whites,  and,  furthermore,  that  the  mortahty  rate 
among  the  former  is  very  considerably  lower  than  in  the  Caucasian  race. 
Minor,-  writing  in  1875,  says:  "The  total  number  of  blacks  d\4ng  of 
scarlet  fever  in  the  Southern  States  was  107  out  of  a  total  black  popu- 
lation of  3,713,327;  so  that  1  out  of  every  34,704  of  the  aggregate 
black  population  died  of  scarlatina.  The  total  number  of  whites  d>ang 
of  scarlet  fever  was  446  out  of  a  total  white  population  of  4,811,962; 
so  that  1  out  of  every  10,790  of  aggregate  white  population  died  of 
scarlet  fever.  It  will  be  at  once  noticed  that  the  disease  is  much  more 
frequent  among  the  whites  than  among  the  colored  population.  During 
epidemics  the  whites  have  seemed  to  be  the  sufferers,  and  there  is 
reason  to  believe  that  there  is  a  certain  immunity  from  epidemic  scar- 
latina existing  among  the  negroes  of  the  South." 

During  the  Civil  War^  378  whites  took  scarlet  fever,  of  whom  70 
died,  and  118  negroes  contracted  the  disease,  of  whom  but  2  died. 
Comparing  the  number  of  the  white  and  black  troops  it  is  seen  that  the 
attack  rate  was  54  in  the  black  race  to  26  in  the  white;  on  the  other 
hand  70  deaths  occurred  among  the  whites  and  only  2  among  the 
negro  soldiers. 

The  United  States  census  of  1870  demonstrated  the  fact  that  the 

1  Meutioned  by  Forchlieimer.    Article  in  Twentieth  Century  Practice  of  Medicine. 

2  Loc.  cit.  3  Medical  and  Surgical  History  of  the  Kebellion,  vol.  iii..  part  i. 

23 


354  SCARLET  FEVER 

foreign-born  population  of  the  country  was  5,567,229,  and  that  1 
out  of  every  6105  died  of  scarlet  fever.  The  population  of  the  native- 
born  whites  was  28,120,788,  of  whom  1  out  of  every  1473  died  of 
scarlet  fever.  The  negro  population  was  4,880,009,  of  whom  1  out  of 
every  16,886  died  of  the  disease. 

It  is  thus  seen  that  scarlet  fever  destroyed,  relative  to  the  population, 
over  ten  times  more  whites  than  negroes.  The  census  statistics  of  1850 
give  somewhat  similar  results. 

The  United  States  census  report  of  1890  shows  a  scarlatina  death  rate 
among  the  whites  of  14.2  per  1000  deaths  from  all  causes  to  2.7  among 
negroes.  The  figures  of  the  1900  census  are  almost  identical — 12.0 
death  rate  among  the  whites  as  compared  with  2.6  among  the  blacks. 
These  statistics  would  indicate  that  the  Caucasian  race  in  the  United 
States  is  six  times  more  susceptible  to  scarlatina  than  the  negroes. 

Inoculability  of  Scarlatinal  Virus. — Attempts,  doubtless  based  upon 
the  success  achieved  by  inoculation  of  smallpox,  have  been  made  to 
induce  a  mild  form  of  scarlet  fever  by  this  process.  These  experiments, 
though  often  contradictory,  have  thrown  some  light  upon  the  etiology 
of  scarlet  fever. 

In  1834  Miquel  reported  to  the  French  Academy  that  he  had  inocu- 
lated a  number  of  children  with  the  fluid  of  scarlatina  vesicles.  The 
rash  was  localized  to  the  region  of  inoculation.  Miquel  alleges  that 
complete  immunity  against  scarlet  fever  was  conferred.  The  reported 
facts  made  it  very  doubtful  that  scarlatina  was  actually  transmitted. 
In  two  cases  inoculated  by  Rostan  the  rash  appeared  seven  days  after 
inoculation.  According  to  the  statement  of  Guersant,^  Petit-Radel  made 
unsuccessfid  attempts  to  produce  scarlatina  by  the  introduction  of 
epidermal  scales  beneath  the  skin  of  previously  unattacked  persons. 

On  the  other  hand,  Stoll  is  reported  to  have  produced  the  disease  by 
rubbing  into  the  skin  scales  from  a  case  of  scarlet  fever.  These  experi- 
ments are  seen  to  be  contradictory  and  permit  no  conclusions  to  be  drawn. 

A  much  more  convincing  case  is  the  accidental  inoculation  of  Dr. 
Rupprecht^  with  mucus  from  the  trachea.  This  physician  had  per- 
formed a  tracheotomy  on  a  mixed  case  of  scarlatina  and  diphtheria. 
In  insufflating  the  lungs  through  an  elastic  catheter,  he  received  some 
mucus  into  the  mouth.  Sixty  hours  later  an  angina  developed  and  in 
seventy-eight  hours  a  chill.  The  eruption  Avas  irregular,  but  the  diag- 
nosis was  said  to  be  certain. 

Recently  some  rather  conclusive  inoculation  experiments  were  carried 
out  by  Stickler^  in  an  effort  to  induce  a  mild  attack  of  scarlet  fever. 
Mucus  from  the  mouth  and  throat  of  scarlatinal  patients  was  mixed 
with  a  1 :  600  solution  of  carbolic  acid  and  injected  subcutaneously 
into  ten  children.  Scarlet  fever  occurred  in  each  child.  The  period  of 
incubation  varied  between  twelve  and  seventy-two  hours,  and  averaged 
thirty-two  hours.     The  author  found  that  the  attacks  were  too  severe  to 

1  Quoted  by  Thomas.    Loc.  cit. 

■■'  Ein  Fall  von  Scharlach.    Wiener  med.  Woch.,  1862.    Hauptblatt,  p.  435. 

3  Medical  Record,  September  9, 1899. 


F/nomciY  355 

warrant  I'nrtlicr  inoculations,  and,  therefore,  (lesisted.  Incidentally  the 
fact  was  proven  that  the  mn(;us  of  the  upper  ;iir  passaj^es  contains  the 
causa  caiuv/n.s  of  the  disease. 

From  the  experiments  (juoted  we  are  not  justified  in  drawing  any 
conclusions  as  to  the  presence  in  the  skin  of  tlif;  infectious  principle. 
A  possibility  of  error,  always  to  be  kept  in  mind,  is  that  persons  inocu- 
lated with  scarlatinal  virus  may  have  contracti^d  the  disease  throuf^li 
exposure  in  the  ordinary  mamier. 

Mode  of  Reception  of  the  Scarlatinal  Infection. — 'J'he  scarlatinal 
poison  is  ordinarily  received  into  the  system  through  the  upper  air 
passages.  It  would  seem  that  the  genital  tract  in  puerperal  women  and 
cutaneous  wounds  may  also  offer  a  point  of  ingress  for  the  infection. 
IJut  in  the  vast  majority  of  cases  the  poison  is  "breathed  in"  just  as 
in  the  other  acute  eruptive  fevers.  Whether  the  virus  effects  its  entrance 
into  the  blood  in  the  lungs,  or  at  some  point  along  the  respiratory 
avenue,  is  a  difficult  question  to  answer.  l)owson,  in  1893,  endeavored 
to  prove  that  the  first  and  essential  localization  of  the  scarlatinal  poison 
was  in  the  throat.  Berge,^  following  this  view,  maintains  that  scarlatina 
is  primarily  a  local  tonsillar  infection,  and  that  the  eruption  both  upon 
the  cutaneous  and  mucous  surfaces  is  the  result  of  the  action  of  an 
erythemogenic  toxin  generated  in  the  tonsils.  The  streptococcus  in  one 
of  its  virulent  forms  is  regarded  as  the  causative  agent  of  the  disease. 
The  view  is  advanced  that  the  infection  may  exceptionally  gain  entrance 
into  the  system  through  other  channels,  as  in  the  case  of  surgical  and 
puerperal  scarlatina.  The  author  cites  a  number  of  cases  to  show  that 
in  puerperal  and  surgical  scarlatina  the  primary  tonsillitis  is  absent, 
although  the  buccopharyngeal  enanthem  may  be  present. 

The  theory  and  facts  presented  by  Berge  are  of  interest,  but  until 
the  cause  of  scarlatina  is  satisfactorily  demonstrated,  we  will  doubtless 
remain  in  ignorance  of  the  site  of  invasion  of  the  scarlatinal  virus. 

Period  of  Infectivity  of  Scarlatina. — In  discussing  this  subject  we 
wish  to  draw  a  distinction  between  the  duration  of  infectiousness  of  the 
scarlatinal  virus  within  and  without  the  patient.  Reference  has  already 
been  made  to  the  longevity  of  the  virus  outside  of  the  human  subject. 
The  contraction  of  the  disease  from  contact  wdth  infected  objects  may 
constitute  a  source  of  error  and  obscure  the  proper  estimation  of  the 
infectious  period. 

There  can  be  no  question  that  at  the  very  beginning  of  scarlatina 
the  contagiousness  is  limited.  We  have  frequently  known  children, 
exposed  to  the  disease  at  the  very  outset,  escape  infection  only  to  contract 
it  when  re-exposed  a  number  of  weeks  later.  Children  wlio  are  im- 
mediately separated  from  a  case  of  scarlet  fever  as  soon  as  it  is  dis- 
covered will  frequently  remain  well;  in  this  respect  scarlet  fever  differs 
strikingly  from  measles,  in  which  disease  the  contagion  is  extremely 
active  even  before  the  appearance  of  the  rash. 

Scarlet  fever  is  highly  contagious  during  the  period  of  eruption  and 

1  Pathogonie  de  la  scarlatiue.    Paris,  1S95,  p.  126. 


356  SCARLET  FEVER 

usually  for  some  time  following  the  disappearance  of  the  rash.  The 
view  has  been  generally  held  that  contagiousness  persists  throughout 
the  entire  stage  of  desquamation,  and  that  the  infectious  principle  is 
resident  in  the  epidermal  scales.  There  have  always  been  some  dissenters 
from  this  view  and  the  doubt  as  to  the  contagiousness  of  desquamating 
epithelium  is  becoming  more  generally  entertained. 

Scarlet  fever  is  not  only  contagious  before  desquamation  begins,  but 
not  infrequently  after  it  has  completely  terminated.  It  is  obvious, 
therefore,  that  the  infection  must  reside  somewhere  in  the  body  apart 
from  the  cutaneous  surface.  Experimental  and  clinical  evidence  both 
point  to  the  throat  and  adjacent  cavities  as  the  probable  lurking  places 
of  the  infectious  organisms.  It  is,  therefore,  of  importance  to  continue 
the  isolation  of  patients  until  discharges  from  the  nose  and  ears  have 
ceased. 

It  is  probable  that  the  prolonged  infectivity  manifested  by  certain 
cases  of  scarlatina  is  due  to  the  presence  of  the  scarlatinal  contagium  in 
the  secretions  of  the  throat  or  in  the  nasal  and  aural  discharges. 

It  is  practically  impossible  to  state  just  at  what  period  a  case  of  scarlet 
fever  ceases  to  be  infectious.  The  more  remote  the  time  from  the  onset 
of  the  disease,  the  greater  is  the  likelihood  of  the  infection  having  been 
extinguished.  Probably  for  this  reason  the  isolating  of  the  patient  for 
the  full  period  of  desquamation  has  been  found  to  be  a  good  working 
rule. 

Physicians  connected  with  scarlet -fever  hospitals  not  infrequently  see 
patients  who  have  remained  in  the  hospital  from  eight  to  twelve  weeks, 
give  rise,  upon  their  return  home,  to  other  cases  in  the  same  household. 
And  this  occurs  despite  the  most  careful  disinfection  of  the  body  and 
the  clothing. 

These  return  cases  occur  in  the  experience  of  many  hospitals  in  from  2 
to  4  per  cent,  of  the  patients.  We  have  seen  patients  at  the  end  of  eight, 
nine,  ten,  and  eleven  weeks,  after  every  vestige  of  desquamation  had 
disappeared,  give  rise  to  the  disease  in  others.  In  a  case  recently 
observed  by  us  we  learned  that,  after  the  dismissal  of  the  child  from  the 
hospital,  the  ear  began  to  discharge  again;  shortly  afterward  a  second 
case  developed  in  the  family. 

Some  years  ago  the  following  sad  case  came  under  observation  at  the 
Municipal  Hospital:  A  child  with  a  well-marked  scarlet  fever  came  to 
the  hospital  at  an  early  stage  of  the  disease,  the  eruption  just  appearing. 
The  patient  remained  in  the  hospital  nine  weeks.  Desquamation  had 
completely  ceased.  An  antiseptic  bath  was  given  in  a  room  disconnected 
from  the  hospital  building,  and  the  child  was  dressed  in  clean  clothing. 
The  patient  had  had  a  discharging  ear  which  had  gotten  well,  but  during 
the  last  bath  slight  moisture  in  the  ear  was  noticed.  A  few  days  after 
the  child's  return,  the  mother  and  two  other  children  were  brought  to 
the  hospital  with  scarlet  fever.  The  attack  in  the  mother  was  severe, 
the  disease  terminating  fatally  in  a  short  time.  The  mother  had  been 
exposed  to  the  child  before  the  latter  was  first  admitted  to  the  hos- 
pital. 


The  Contagiousness  of  Desquamating  Epithelium. — Almost  thirty 

years  af^o  Thomas  wrote:  "'J'lie  eonta^ioiisiiess  oi"  the;  postexanthernatic 
period  is  usually  ascril)e(l  to  th(;  scales  of  e})i(h^ririis  wliieh  separate 
during  the  process  of  desfjuamation;  hut  it  seems  to  me  that  there  is 
not  the  shadow  of  evidence  to  prove  that  the  contagion  is  contained  n 
them  either  exclusive'y  or  even  chiefly;  for  it  may  be  presumed  that  the 
contag  on  enters  from  the  l)lood  into  all  secretions  and  excretions  of  the 
patient.  Volz,  in  fact,  totally  denies  the  contagiousness  of  the  epidermal 
desquamation." 

Von  Kerchnsteiner  states  that  "the  most  favorable  conditions  for 
contagion  exist  during  the  stage  of  eruption  and  acme  of  the  exanthem ; 
the  most  unfavorable  dui'ing  desquamation." 

(This  subject  is  more  fully  discussed  in  the  chapter  on  treatment.) 

There  is  no  evidence  to  indicate  that  the  scarlet  fever  contagium  is 
disseminated  by  aerial  transmission.  The  immediate  vicinity  of  scarlet- 
fever  hospitals  appears  to  be  as  free  of  the  disease  as  other  .sections  of 
the  city.  In  this  respect  scarlet  fever  differs  from  smallpox,  in  which 
disease  the  territory  immediately  surrounding  the  hospital  is  apt  to 
show  a  disproportionately  large  number  of  smallpox  cases. 

The  following  figures  are  taken  from  the  Medical  and  Surgical  Reports 
of  the  Boston  C a y  Hospital,  1897: 

Radius  of  one-eighth      of  a  mile  from  scarlet-fever  hospital  .  .       0  cases. 

"       "    one  quarter       "  "    "        "           "       "           "         .  .  6h 

"      "    one-half            "  "    "       "           ■'        "           "         .  .  71      " 

"       "    three-quarters "   "    "        "           "        "            "         .  .  75      " 

"       "    one                              "       "           "        "           "         .  .  72      " 

Within  one  mile  of  the  hospital 2^6      " 

Beyond  the  one-mile  limit 756      " 

It  is  seen  from  the  above  figures  that  no  cases  developed  within  the 
one-eighth  mile  limit  about  the  hospital. 

Our  experience  at  the  Municipal  Hospital  would  lead  us  to  believe 
that  the  striking  distance  of  scarlet  fever  is  extremely  limited. 

It  has  been  exceedingly  rare  for  families  in  the  immediate  vicinity  of 
the  hospital  to  become  attacked  with  scarlet  fever,  although  they  have 
not  escaped  smallpox. 

The  fact  that  scarlet  fever  is  not  carried  beyond  the  confines  of  the 
hospital  walls  rather  militates  against  the  view  of  the  infectivity  of 
scales,  for  in  a  scarlet-fever  ward  the  air  contains  myriads  of  minute 
particles  of  desquamating  epithelium. 

Scarlet-fever  Infection  in  Milk. — The  transmission  of  the  infection 
of  scarlet  fever  in  milk  has  attracted  the  attention  of  physicians  for 
some  years. 

Thomas,  wa-iting  in  1875,  referred  to  two  epidemics  reported  by 
Bell  and  Taylor  in  which  the  dissemination  of  the  disease  was  ascribed 
to  infected  milk.  In  the  latter  epidemic  one  of  the  first  cases  of  scarlatina 
occurred  in  the  family  of  a  milkman  whose  wife  milked  the  cows.  The 
milk  was  supplied  to  twelve  families,  in  six  of  which  scarlatina  appeared 
in  rapid  succession,  without  contact  with  the  milk  server,  and  at  a  time 


358  SCARLET  FEVER 

when  the  disease  was  not  epidemic.  The  milk  had  been  kept  in  a 
kitchen  in  which  scarlatinous  patients  had  been  treated. 

In  1886  Power^  observed  in  London  a  severe  epidemic  of  scarlet  fever 
which  appeared  to  attack  in  particular  the  patrons  of  Hendon  Farm, 
whose  cows  were,  suffering  from  a  peculiar  malady.  This  disease  was 
studied  by  Klein/  who  came  to  the  conclusion  that  the  animals  were 
suffering  from  scarlet  fever,  and  that  the  infection  was  conveyed  in  the 
milk  to  human  subjects.  The  malady  was  introduced  among  the  cows 
by  an  animal  which  had  elevation  of  temperature,  cough,  faucial  and 
oculonasal  catarrh,  a  red  rash  about  the  eyes  and  on  the  inside  of  the 
thighs,  followed  two  weeks  later  by  desquamation  and  loss  of  hair. 
Vesicopustules  were  present  upon  the  udders,  which  later  gave  rise  to 
ulcers.  The  animal  had  recently  given  birth  to  a  calf.  Klein  found 
streptococci  in  the  serum  from  the  vesicles  which  he  inoculated  into 
animals.  He  likewise  found  streptococci  in  the  blood  of  some  scarlatina 
patients.  This  organism  he  regarded  as  the  specific  cause  of  scarlet 
fever. 

In  the  same  year  Crookshank  and  Brown^  noted  an  epidemic  among 
cows  analogous  to  that  observed  by  Klein.  After  carefully  studying 
the  same  and  making  further  inoculations  from  an  accidentally  received 
sore  on  the  hand  of  a  dairyman,  they  proved  that  the  disease  was  cowpox. 
The  same  streptococcus  was  obtained  by  culture.  i 

In  1885  an  epidemic  of  scarlet  fever  occurred  in  Rostock,  Germany, 
apparently  from  milk  infection.*  A  very  striking  increase  in  scarlet  fever 
occurred  in  June,  in  which  month  36  cases  developed.  It  was  dis- 
covered that  the  families  (with  two  or  three  exceptions)  were  supplied 
with  milk  from  a  farm  in  the  village  of  Gehlsdorf,  where  6  cases  of 
scarlet  fever  and  a  number  of  cases  of  sore  throat  existed  among  the 
farmers'  families  and  employes.  Some  of  those  who  were  taken  ill  had 
milked  the  cows  and  had  handled  the  milk.  According  to  the  investiga- 
tions of  the  Rostock  physicians,  8  of  the  36  cases  could  with  certainty 
be  attributed  to  infection  from  the  milk.  As  indicating  the  presence 
of  the  infecting  agent  in  the  milk,  it  was  noted  that  those  who  drank 
boiled  milk  escaped;  this  was  the  case  in  two  children,  two  and  four 
years  of  age,  who  remained  free,  although  other  children  in  the  same 
household  who  drank  raw  milk  contracted  the  disease. 

Freeman^  has  made  a  careful  study  of  the  transmission  of  various 
diseases  through  infected  milk.  He  states  there  is  conclusive  evidence 
that  contaminated  milk  has  caused  certain  epidemics.  In  26  recent  epi- 
demics of  scarlet  fever  in  England  traceable  to  milk,  15  were  found  to 
be  due  to  the  disease  in  man. 

Epidemics  due  to  infected  milk  have  within  recent  years  been  reported 

1  Milk  Scarlatina,  London.  Report  of  the  Medical  GfiBcer  of  the  Loral  Government  Board,  Feb- 
ruary, 1885  and  1886,  No.  8,  p.  73. 

-  The  Etiology  of  Scarlet  Fever.    Proceedings  of  the  Royal  Society  of  London,  1887,  xlii. 

3  Communication  to  the  Pathological  Society  of  London,  1887. 

<  Quoted  by  von  Jiirgensen.    Loc.  cit.,  p.  413. 

5  Medical  Record,  March  28,  1896.  Quoted  by  Northrup  in  von  Jiirgensen's  article  on  "Scarlet 
Fever."    Loc.  cit.,  p.  414. 


i<:ti()L()(1  y  359 

in  this  country.  In  Plainficld,  New  Jersey,  an  epidemic  wastra  eed  to  a 
farm  hand  who  had  a  mild  attack  of  ,s(;arlet  fever  ntifl  who  liandled  the 
milk  (hirinfij  this  tinu^ 

More  rec(Mitly  iin  ontl)r(>a,k  of  scarlet  fever  occurred  ainf)n^  .'>o  students 
of  Purdue  University,  Lafayette,  Indiana.  The  i^o  cases  wen;  fed  at 
eleven  different  boanhng  houses,  all  of  which  were  supplied  with  milk 
by  the  same  dairyman.  Five  private  families  supplied  with  the  same 
milk  had  one  or  more  cases  of  the  disease  in  their  househftids.  The 
infec'tion  was  attributed  to  winter  c-jothin^  which  had  just  been  f)ut  on, 
and  which  had  been  laid  away  the  March  before,  at  which  time  the 
"dairyman's  family  ran  through  a  course  of  scarlet  fever." 

From  the  now  extensive  literature  upon  the  subject,  we  may  conchule 
that  scarlatina  may  be  conveyed  through  a  contaminated  milk  supply. 
The  proposition  is  not  proven  beyond  the  peradventure  of  a  douljt,  but 
the  chain  of  circumstantial  evidence  is  so  strong  as  to  render  this  con- 
clusion almost  irresistible.  It  would,  furthermore,  appear  that  the 
milk  is  contaminated  through  contact  with  an  individual  suffering  or 
convalescent  from  the  disease.  The  view  advanced  by  Klein  that  the 
cows  themselves  suffer  from  scarlatina  remains  unproven  and  is  not 
generally  credited. 

Hall,^  in  reviewing  the  subject  of  milk  infection,  makes  the  following 
interesting  statement:  "While  scarlet  fever  occurs  in  epidemic  form  in 
those  countries  where  cows'  milk  forms  a  staple  article  of  food,  espe- 
cially among  children,  it  does  not  occur  in  countries  where  cows'  milk 
is  not  used  as  a  food,  or  where  children  are  raised  upon  mothers'  milk 
only."  In  Japan  cows'  milk  is  not  used,  and  scarlet  fever  is  practically 
an  unknown  disease  there.  In  India,  cows'  milk  is  used,  but  children 
are  kept  at  the  maternal  breast  until  they  are  three  or  four  years  of  age. 
Scarlet  fever  is  a  rare  disease  in  India,  seldom  occurring  in  epidemic 
form. 

Pregnancy  and  the  Puerperium, — It  cannot  be  said  that  pregnancy 
increases  the  predisposition  to  scarlet  fever,  for,  according  to  Senn, 
Tourtual,  and  Trousseau,  no  case  of  scarlet  fever  in  pregnant  women 
was  observed  by  them  during  extensive  epidemics  of  the  disease.  That 
scarlet  fever  is  an  excessively  rare  occurrence  during  pregnancy  is 
evidenced  also  by  the  statement  of  Olshausen  that  he  was  able  to 
find  only  seven  cases  in  medical  literature.  When  scarlet  fever  does 
complicate  gestation  it  is  prone  to  lead  to  abortion  or  premature  delivery. 

Great  diversity  of  opinion  is  expressed,  in  the  extensive  literature^ 
on  the  so-called  'puerperal  scarlatina,  as  to  the  real  nature  of  this  affection. 

Malfatti^  in  1801  published  an  account  of  a  malignant  scarlet  fever 
epidemic  which  prevailed  among  puerperal  women  in  confinement  in 
Vienna.  The  symptoms  were:  offensive  lochial  discharge,  abdominal 
tenderness,  with  later   (between  the  second  and  seventh  days  after 

1  New  York  Nfedical  Record,  November  11,  1S99. 

"  An  admirable  collation  of  the  literaiure  on  this  subject  is  presented  by  Marcel  Durand  in  a 

Paris  thesis  entitled  "  Etude  hislorique  et  critiqne  sur  la  scarlatina  pnerperale."    Pp.  3J5.   Paris,  1S91. 

'■>  Journal  der  prakt.  Heilkunde,  by  C.  \V.  Uufeland,  Bd.  xii.,  part  iii.  p.  VJO.    Berlin,  Ungar,  ISOl. 


360  SCARLET  FEVER 

delivery)  chills,  headache,  ringing  in  the  ears,  hot  skin,  nervousness, 
and  moderately  rapid  pulse;  then  a  diffuse  reddish  exanthem,  which 
on  the  third,  fourth,  or  fifth  day  became  bluish,  accompanied  by  marked 
nervous  symptoms,  failure  of  the  vital  powers,  and  death. 

In  1875  Braxton  Hicks  read  before  the  London  Obstetrical  Society  a 
paper  in  which  he'  stated  that  of  89  puerperal  cases  under  his  care  that 
had  febrile  symptoms,  he  regarded  37  as  suffering  from  scarlet  fever. 
Very  few  of  these  patients  had  an  angina  of  any  severity  and  17  did  not 
have  an  eruption.  In  2  instances  scarlet  fever  developed  in  children 
who  were  exposed  to  the  puerperal  women.  In  the  discussion  that 
followed,  some  endorsed  but  many  repudiated  the  diagnosis  of  scarla- 
tina in  these  puerperal  fevers. 

Olshausen^  combats  the  contention  of  Hicks  and  mentions  the  argu- 
ments which  led  Helm  and  subsequent  writers  in  Germany  to  regard 
puerperal  fever  with  scarlatiniform  rash  as  puerperal  septicaemia:  (1) 
these  epidemics  occur  in  maternities  and  not  synchronously  with 
outside  epidemics;  (2)  the  malady  has  a  malignity  more  in  accord  with 
puerperal  septicaemia;  (3)  it  is  often  complicated  with  peritonitis  and 
other  manifestations  analogous  to  those  seen  in  puerperal  fever;  (4) 
origin  in  the  early  days  of  the  post-partuvi  as  is  observed  in  septicaemia; 
(5)  in  the  majority  of  cases  it  has  been  impossible  to  establish  contagion. 

Olshausen  collected  141  cases  of  scarlatiniform  rash  occurring  during 
pregnancy  and  the  puerperium;  these  were  reported  by  Koch  (3), 
Schneider  (5),  Clemens  (2),  Simpson  (2),  Hardy  (2),  MacClintock  (34), 
Brown  (9),  Johnston  and  Sinclair  (2),  Winkel,  Halahan  (25),  Hicks  (18), 
Lange,  Denham  (8),  Senn  (7),  Dance  (1),  Trousseau  (1),  Gueinot  (4), 
Hervieux  (7),  and  Olshausen  (5).  Of  this  number  only  six  occurred 
during  pregnancy.  Eight  developed  immediately  after  confinement,  62 
from  the  first  to  the  second  day  after  confinement,  27  the  third  day,  and 
22  from  the  third  to  the  eighth  day  afterward. 

Winckel,^  in  expressing  his  incredulity  concerning  the  scarlatinal 
nature  of  Hicks'  cases,  mentions  the  fact  that  lying-in  women  in  England 
more  frequently  exhibit  an  erythema  upon  the  cutaneous  surface  than 
in  Germany. 

Martin^  is  of  the  same  opinion  and  regards  true  puerperal  scarlatina 
as  a  rare  occurrence.  Indeed,  in  38,000  accouchements  he  observed  this 
complication  but  three  times. 

Von  Jiirgensen,  after  a  careful  study  of  Malfatti's  cases,  does  not 
regard  them  as  true  scarlatina,  but  as  puerperal  septicaemia.  He 
believes  that  scarlatina,  in  the  strict  meaning  of  the  term,  is  of  slight 
significance  as  a  factor  in  the  mortality  of  the  puerperium. 

The  fact  is  recognized  that  puerperal  septicaemia  may  be  attended 
with  a  rash  which  cannot  be  distinguished  from  that  of  scarlet  fever. 
The  lying-in  woman  may  develop  after  confinement  either  a  true  scarlet 
fever  or  a  puerperal  fever  with  a  septic  scarlatiniform  rash.    There  can 

1  Archiv  llir  Gyntikol.  und  Obstet.  de  Cred(§,  1876. 

2  Die  Pathologie  und  Therapie  des  Wochenbettes,  third  edition,  p.  350.    Berlin,  Hirschwald,  1875. 

3  Zeitschr.  fiir  Geburtsh.  und  Gynitkol.,  1876,  vol.  ii. 


ETIOI/XIY  301 

be  no  doubt  that  in  the  past  many  instances  of  the  IjiUcr  ffjitflition  have 
been  regarded  as  puerperal  srarlatina.  Tlie  fliflereiilial  diaj^nosis  is 
often  extremely  difliciilt.  The  following  points  would  indicate  a  puer- 
peral infection  rather  tiian  scarlet  fever: 

1.  The  absence  of  an  epi<lemic  of  scarlatina  and  c)f  any  history  of 
scarlatinal  infection. 

2.  The  presence  of  lesions  of  the  genital  tract,  such  as  inflammation 
in  and  around  the  uterus.  In  puerj)eral  infection  metritis  and  peri- 
tonitis are  more  (-ommonly  found  than  in  scarlatina  after  confinement. 

3.  In  puerperal  septica?mia  the  rash  is  often  irregular.  It  may  be 
circumscribed  to  the  lower  portion  of  the  abdomen;  in  some  cases  it  is 
morbilliform.  When  it  is  diffuse  and  scarlatiniform  in  character,  the 
spread  over  the  body  is  usually  more  rapid  than  in  true  scarlatina. 
Occasionally  the  rash  may  reappear  even  as  often  as  seven  times,  as 
reported  by  Lucas-Championniere. 

4.  The  associated  symptoms  seen  in  scarlatina  are  only  imperfectly 
present.  Angina  is,  as  a  rule,  slight  or  absent;  the  straw-berry  tongue  is 
not  seen;  renal  complications  are  rare  and  desquamation  is  usually 
branny  instead  of  lamellar. 

5.  The  mortality  is  lov^er  in  true  scarlatina  than  in  puerperal  fever 
v^ith  septic  rash.  Among  the  141  cases  collected  by  Olshausen,  of  fever 
and  scarlatiniform  rash  occurring  in  puerperal  women,  the  mortality 
v^^as  over  50  per  cent. 

In  doubtful  cases  the  history  of  a  previous  attack  of  scarlatina  in  the 
patient  vi^ould  constitute  presumptive  evidence  against  the  existence  of 
this  disease. 

It  is  important  to  bear  in  mind  that  in  certain  subjects  the  employment 
of  intrauterine  or  even  vaginal  irrigations  of  bichloride  of  mercury  may 
provoke  the  appearance  of  scarlatiniform  rashes  v^hich  may  be  regarded 
as  septic  or  may  be  confounded  with  scarlatina. 

Surgical  Operations. — It  would  appear,  from  the  rather  convincing 
case  of  Prof,  von  Leube  (mentioned  on  page  346),  and  from  occasional 
epidemics  in  surgical  wards  of  hospitals  (such  as  that  reported  by 
Howse^  occurring  in  Guy's  Hospital),  that  the  scarlet -fever  poison  may 
at  times  gain  entrance  into  the  system  through  wounds. 

Furthermore,  it  is  probably  true  that  persons  who  have  undergone  a 
surgical  operation  have  less  resisting  power  to  the  scarlatinal  infection 
than  healthy  persons.  This  view  is  held  by  Thomas,  who  says:  'Tt  really 
seems  as  if  such  persons,  in  consequence  of  their  general  condition, 
possessed  a  greater  susceptibility  to  the  disease." 

The  total  number  of  cases  of  scarlet  fever  which  developed  during 
the  course  of  twenty  years  among  surgical  cases  in  the  great  St.  Ormond 
Street  Hospital  in  London  was  163.  Sir  James  Paget  in  1S63,  in  a 
lecture  given  at  St.  Bartholomew's  Hospital,  referred  to  10  cases  of 
scarlatina  which  he  had  observed  after  operation. 

In  a  boy  upon  whom  a  lithotomy  had  been  performed,  the  rash  of 

1  Some  account  of  an  epidemic  of  surgical  scarlatina  occurring  in  Astley  Cooper  Ward  in  1S7S, 
with  remarks.    Guy's  Hospital  Reports,  London,  1S79,  xxiv.  pp.  44-462. 


362  SCARLET  FEVER 

scarlet  fever  appeared  upon  the  day  after  the  operation.  Paget  noted 
the  brevity  of  the  period  of  incubation  in  these  cases,  8  of  them  being 
under  three  days.  He  thought  it  probable  that  the  patients  had  received 
the  infection  before  the  operation  and  that  the  manifestation  of  the 
disease  would  not  have  appeared  so  soon,  or  possibly  not  at  all,  if  the 
health  had  not  been  disturbed  by  operative  interference. 

Gerasimovitch  states  that  out  of  2000  patients  operated  on  in  the 
Children's  Hospital  at  St.  Petersburg  between  1897  and  1902,  44 
developed  so-called  surgical  scarlatina.  In  8  of  the  cases  the  period 
of  incubation  was  less  than  twenty-four  hours. 

Stirling,^  in  an  exhaustive  article  on  surgical  scarlatina,  reports  7 
cases  of  scarlet  fever  occurring  after  circumcision. 

Hoffa,^  of  Wiirzburg,  discusses  the  subject  of  rashes  following  surgical 
procedures.  Many  of  these  are  regarded  by  him  as  scarlatinoid  ery- 
thema simulating  scarlet  fever.  He  believes,  however,  that  he  has  seen 
several  cases  of  genuine  scarlet  fever  develop  after  surgical  operations. 

Operations  upon  the  throat  have  not  infrequently  been  followed  by 
attacks  of  scarlet  fever  and  by  rashes  simulating  it.  Lennox  Browne 
states  that  "after  removal  of  chronically  enlarged  tonsils,  symptoms  of 
pyrexia,  rash,  and  desquamation,  which  are  practically  identical  with 
scarlatina  are  exhibited  occasionally." 

Wingrave^  reports  thirty-four  rashes  in  patients  operated  upon  for 
removal  of  tonsils  and  adenoids,  during  a  period  of  seven  years. 

Fisher*  saw  3  cases  of  scarlet  fever  following  the  removal  of  the 
tonsils  and  adenoids.  In  1  case  the  early  symptoms  were  severe  and 
were  followed  later  by  double  otitis  media  and  nephritis. 

We  have  within  the  past  few  years  observed  4  cases  of  scarlet  fever 
after  surgical  operations.  One  followed  circumcision,  1  an  operation 
for  deviation  of  the  nasal  septum,  1  an  excision  of  cervical  glands,  and 
1  after  an  operation  for  pyosalpinx. 

We  have  also  observed  an  attack  of  scarlatina  following  rapidly  upon 
a  hum.  A  colored  child  was  admitted  to  the  Pqlyclinic  Hospital  suffering 
from  a  deep  burn  of  the  face  and  arm.  About  twenty-four  hours  after 
admission  the  temperature  rose  to  105°  F.  and  a  scarlatiniform  rash 
appeared  upon  the  body.  Nothing  characteristic  was  observed  in  the 
throat  or  upon  the  tongue.  The  diagnosis  was  reserved,  inasmuch  as 
the  symptoms  might  well  have  been  attributed  to  an  intoxication  due 
to  the  burn.  The  child  was  isolated  and  a  special  nlirse  assigned  to 
look  after  it.  In  about  four  days  this  nurse  contracted  a  well-pronounCed 
attack  of  scarlet  fever. 

Two  distinct  and  separable  conditions  have  doubtless  been  included 
in  the  term  "surgical  scarlatina."  There  can  be  no  question  that  some 
of  the  rashes  developing  after  operations  represent  the  exanthem  of 
genuine  scarlet  fever.    On  the  other  hand,  a  certain  proportion,  doubt- 

1  St.  George's  Hospital  Reports,  1879,  vol.  x. 

'  Volkmann's  Sammlungklin.  Vortrilge,  1686  and  1887,  No.  29. 

2  Tonsillotomy  Rash.    The  Laryngoscope,  1901. 
<  The  Laryngoscope,  May,  1904. 


77//';  HYMPT()MAT()[/)(IY  OF  SCAKLF/r  FFVFIi  363 

less,  are  loxir  or  S('[)(ic  scaHaliiioid  cryflicinas  wliirh  are  iiiirclaffd  io 
true  scarlalirui,. 

The  diagnosis  should  ncv(M-  ]h\  iiKuh-  upon  (he  cmijlion  iilone,  iV>r  a 
septic  rash  may  he  (jiiite  indisliiif^iiishiihle  from  that,  of  s(;arlet  fever. 
The  general  symptoms  must  he  considered  and  the  condition  of  the 
throat,  tongue,  glands,  ears,  and  kidneys  determined  in  order  to  throw 
the  full(\st  light  n])on  these  diriicult  cases. 

The  diiignosis  of  scarlatina  is  sometimes  indnhitahly  confirmed  hy 
the  unfortunate  transmission  of  the  (hsease  to  another  subject. 

THE   SYMPTOMATOLOGY  OF   SCARLET  FEVER. 

Period  of  Incubation. — By  the  period  of  incubation  is  meant  the  time 
elapsing  between  the  reception  of  the  scarlatinal  poison  into  the  .sy.stem 
and  the  first  manifestation  of  symptoms  of  the  disease.  It  is  well  to 
bear  the  fact  in  mind  that  the  reception  of  the  contagion  is  not  invariably 
coincident  with  the  exposure  to  the  disease. 

The  breeding  stage  of  scarlatina  is  briefer  and  at  the  same  time  more 
variable  than  that  of  the  other  acute  exanthemata.  Within  its  com- 
paratively narrow  hmits,  a  considerable  degree  of  variation  occurs. 
The  incubation  stage  of  smallpox,  although  extending  over  a  longer 
period,  is  strikingly  uniform  and  reliable;  to  be  sure,  there  are  some 
variations,  but  these  constitute  exceptions.  Measles,  too,  has  a  com- 
paratively constant  period  of  incubation. 

The  various  writers  on  scarlet  fever,  in  giving  expression  to  their 
views  as  to  the  duration  of  the  incubation  stage,  are  guided  largely  l)y 
their  individual  experiences.  Apart  from  actual  differences  in  the 
clinical  experiences  of  physicians,  some  of  the  widely  divergent  incubation 
periods  may  possibly  be  attributed  to  differences  in  the  discriminating 
judgment  of  the  observers.  The  more  conservative  writers  are  in 
general  agreed  that  the  most  common  period  of  incubation  of  scarlet 
fever  is  between  three  and  seven  days;  the  narrower  these  limits  are  con- 
tracted as  a  general  proposition,  the  greater  is  the  liability  to  error. 
Thomas  regards  "four  to  seven  days  as  the  most  frequent  interval," 
and  looks  upon  shorter  or  longer  periods  as  exceptions  to  the  rule. 
Von  Leube  and  Forchheimer  both  subscribe  to  this  estimate.  Vogl 
believes  that  the  exanthem  appears  three  or  at  most  five  days  after 
infection. 

While  these  intervals  cover  the  vast  majority  of  cases,  there  have  been 
recorded  occasional  authentic  instances  of  much  shorter  and  longer 
periods  of  incubation.  Trousseau's  case  of  not  more  than  twenty-four 
hours'  incubation  is  of  interest.  He  writes:  "A  London  merchant  had 
taken  one  of  his  daughters  to  the  Eaux  Bonnes  in  the  Pyrenees,  and  had 
passed  the  winter  with  her  at  Pau.  On  his  way  back  to  London  he 
stopped  at  Paris,  where  he  wished  to  remain  some  days.  His  eldest 
daughter  was  keeping  house  for  him  in  London.  Impatient  to  embrace 
her  father  and  sister,  she  started  for  Paris.  When  crossing  the  channel, 
she  was  seized  with  fever  and  sore  throat,  and  seven  or  eight  hours  later 


364  ■  SCARLET  FEVER 

arrived  at  Paris  in  the  middle  of  a  very  serious  attack  of  scarlet  fever. 
She  alighted  at  the  hotel,  almost  at  the  very  moment  when  her  father 
and  sister  arrived  from  Pan.  The  two  sisters  remained  together  in  the 
same  room,  and  in  twenty-four  hours  the  sister  who  had  come  from  Pau 
showed  the  first  symptoms  of  a  mild  attack  of  scarlatina.  In  London 
the  disease  was  then  epidemic,  but  there  were  no  cases  at  Pau." 

Trojanowsky,  Forster,  Sorensen,  Murchison,  Alonzo  Clark,  Raven, 
Hagenbach-Burkhardt,  and  others  have  recorded  periods  of  incubation 
of  twenty-four  hours  or  even  less;  so  that  it  may  be  accepted  that  in 
rare  cases  the  infection  may  give  rise  to  symptoms  almost  immediately 
after  entrance  into  the  system. 

As  to  long  periods  of  incubation,  there  is  much  divergence  of  opinion. 
Veit  claims  it  may  be  twelve  to  fourteen  days;  Paasch  published  a  case 
in  which  it  was  twelve  days;  Gerhardt  and  Reinhold  credited  periods 
of  eleven  to  thirteen  days.  Bawy  records  an  instance  of  twenty-one 
days  and  Trojanowsky  one  of  twenty-eight  days. 

Murchison,  in  his  wide  experience,  has  only  been  able  to  collect  a 
series  of  13  cases  in  which  he  could  be  sure  of  the  incubation  period; 
in  not  a  single  one  of  these  cases  was  the  period  longer  than  six  days. 

On  the  other  hand,  Hagenbach-Burkhardt^  reports  57  cases  in  which 
he  has  been  able  to  study  the  incubation  period.  Of  this  group  the 
remarkable  number  of  35  had  incubation  stages  of  over  seven  days. 
Under  eight  days  there  were  4  cases;  nine  days,  2  cases;  ten  days,  1  case; 
eleven  days,  5  cases;  twelve  days,  1  case;  thirteen  days,  4  cases;  fourteen 
days,  2  cases;  fifteen  days,  5  cases;  seventeen  days,  2  cases;  eighteen 
days,  1  case;  nineteen  days,  2  cases;  and  over  twenty  days,  6  cases. 
This  is  certainly  a  most  remarkable  array  of  long  incubation  periods  to 
come  within  the  experience  of  any  one  observer. 

Some  of  these  instances  and  others  exhibiting  long  periods  of  incu- 
bation may  possibly  be  explained  upon  the  grounds  of  a  temporary 
immunity  retarding  the  susceptibility  to  the  scarlet-fever  poison.  While 
unprotected  individuals  are  almost  invariably  susceptible  to  the  con- 
tagion of  smallpox  and  measles,  the  same  is  not  true  of  scarlet  fever. 
Certain  individual  conditions  about  which  little  is  known  seem  to  make 
some  persons  immune  at  one  time  and  susceptible  at  another  to  the 
infection  of  scarlet  fever. 

We  have  recently  had  the  opportunity  of  watching  a  protracted 
epidemic  of  scarlet  fever  in  a  home  for  children  in  this  city.  For  a 
period  of  over  three  months,  children  contracted  the  disease  two  or . 
three  at  a  time  and  were  sent  to  the  Municipal  Hospital.  About  40 
out  of  100  were  thus  gradually  attacked.  It  would  seem  that  in  many 
of  the  children  the  individual  susceptibility  was  temporarily  in  abeyance 
or  that  the  infection  was  not  received  by  them  in  the  beginning  in 
suflflciently  intense  or  concentrated  form. 

It  is  alleged  by  some  writers  that  a  virulent  contagium  may  shorten 
the  period  of  incubation,  and  that  a  similar  abbreviation  of  this  stage 
may  result  when  the  scarlatina  occurs  in  a  surgical  or  puerperal  subject. 

1  Ueber  Spital  iafectiouea,  Jahrbuch  fiir  Kiaderheilk.,  Bd.  xxiv.  p.  105. 


Tim  SYMPTOM  A  TOLOflY  OF  liCAHLF/r  FKVRH 


365 


Holt/  has  tabulated  records  of  the  incubation  periorj  in  113  cases, 
some  of  which  were  ol).served  by  him,  but  most  of  which  have  been 
abstracted  from  the  literature  of  the  subject: 


iNfJur.ATioN  Pkrioo. 


24  hours  or 

lesK  . 

.     6  cases. 

7  flays     . 

8  cajeR 

2  days 

.    15     " 

8    "         .        . 

.      2     " 

3    " 

.    28      " 

9    "         .        . 

.      5      " 

4    " 

.     2.')       " 

11    " 

1  case. 

5    " 

.       6      " 

14    " 

.     1    " 

6    " 

.     15      " 

21     " 

.     1    " 

It  is  seen  that  in  87  per  cent,  of  these  cases  the  incubation  period  was 
between  two  and  six  days. 

Simple,  Usual,  or  Normal  Scarlatina  (Scarlatina  Simplex). 

Period  of  Invasion. — During  the  stage  of  incubation  no  symptoms, 
as  a  rule,  are  present,  the  morbid  process  being  entirely  latent.    The 


Fic 

.  59 

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Temperature  and  pulse  record  of  scarlatina  simplex.    J.  B.,  aged  six  years ;  mild  case  of  scarlet 
fever  terminating  in  recovery. 

onset  of  the  disease  is  sudden.  The  earliest  symptoms  are :  indisposition, 
fever,  headache,  vomiting,  and  sore  throat.     Chills  are  usually  absent 

1  Piseases  of  Infancy  and  Childhood,  Xew  York,  1896,  p.  889, 


366  SCARLET  FEVER 

except  in  severe  cases.  In  children  vomiting  is  the  earhest  as  wel  as 
the  commonest  of  the  invasive  symptoms,  and  is,  therefore,  of  suggestive 
diagnostic  import.  Not  infrequently  children  in  the  full  bloom  of 
health  are  quite  suddenly  seized  with  vomiting  rapidly  followed  by 
the  other  symptoms  of  scarlatina.  Billington  observed  this  symptom  in 
about  80  per  cent,  of  his  cases.  We  have  obtained  a  history  of  the 
occurrence  of  emesis  in  76  out  of  155  cases,  or  about  50  per  cent.  We 
believe  that  the  average  frequency  of  this  symptom  is  greater  than 
would  be  indicated  by  these  figures.  The  evacuation  of  the  contents 
of  the  stomach  may  be  accompanied  by  diarrhoea,  although  usually  the 
bowels  are  constipated.  In  severe  cases  in  infants  convulsions  are  not 
uncommon.  There  is  loss  of  appetite  and  the  tongue  is  furred.  Adults 
and  older  children  who  are  able  to  appreciate  the  sequence  of  the 
symptoms  often  indicate  sore  throat  as  the  first. 

Temperature. — The  temperature  rises  rapidly,  often  reaching  102°  to 
104°  F.  or  more  in  the  course  of  a  few  hours.  The  pulse  increases  in 
frequency  and,  compared  with  the  temperature,  is  often  disproportion- 
ately rapid.  The  radial  pulsations  may  number  in  children  140  to  160 
per  minute,  and  in  adults  120  to  140. 

Headache  and  vertigo  are  common,  and  the  patient  may  be  alternately 
somnolent  and  restless.  The  thirst  is  often  intense.  The  patient  is 
greatly  prostrated  and  presents  the  facies  of  a  very  sick  person.  The 
skin  is  hot  and  dry,  the  eyes  dull  and  listless,  and  the  face  flushed. 

The  fever  in  scarlatina  is  subject  to  great  variations,  being  influ- 
enced by  the  severity  of  the  epidemic  and  the  nature  of  the  accom- 
panying complications.  The  pyrexial  curve  is  by  no  means  as  constant 
as  is  seen  in  the  other  two  important  exanthematous  diseases — smallpox 
and  measles. 

Wunderlich^  gives  the  following  as  the  average  febrile  course:  The 
temperature  at  the  onset  of  the  disease  rises  rapidly,  and  after  a  few 
hours  reaches  104°  to  105°  F.  or  higher.  With  slight  morning  remissions 
the  fever  still  increases  from  the  appearance  of  the  eruption  until  its 
complete  diffusion  over  the  surface.  When  the  eruption  has  reached 
its  height,  the  temperature  begins  to  decline  by  gradual  steps,  with 
slight  evening  exacerbations. 

It  is  thus  seen  that  the  fever  is  a  continued  one  during  the  invasive 
and  early  eruptive  period,  and  that  the  pyrexia  subsides  by  lysis  con- 
currently with  the  fading  of  the  exanthem. 

In  well-pronounced  cases  of  what  might  be  called  the  normal  form 
of  scarlet  fever  the  early  rise  of  temperature  is  seldom  below  104°,  and 
it  not  infrequently  reaches  105°  or  106°  F.  The  high  temperature 
persists  ordinarily  for  four  or  five  days  and  then  a  decline  sets  in. 

The  intensity  and  the  duration  of  the  fever  depend  much  upon  the 
type  of  the  prevailing  epidemic.  We  have  determined  the  duration  of 
the  fever  in  265  cases  of  scarlatina  which  we  treated  in  the  winter  of 
1902-03,  at  which  time  the  type  of  the  disease  was  distinctly  mild. 

1  Eigenwarme  in  Krankheiten, 


77//';  H^YMPTOMATOLOCY  OF  SCAULh'/r  /''/'JVh'ii 


Wl 


Tetn[)()riuy   ri.ses   of   tern[)eratiire   occurring   late   and    resulting    fio 
recognized  c()iiif)li("itioii,s  or  .s('f|U(!lir'  were  not  consifjcrefj. 


Ki(..  00 


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R.  B.,  aged  seven  years  ;  case  of  scarlet  fever  with  an  intense  rash  and  severe  early  symptoms, 
terminating  rather  unusually  by  crisis. 


DuEATiox  OF  Fever  in  265  Cases  of  Scarlet  Fevfr  Treated 
Municipal  Hospital  in  the  Winter  of  1902-03. 


AT   THE 


Lasting 


1  day 

.      2 

2  days 

.       3 

3    " 

.    17 

4    " 

.    19 

5    " 

.    32 

6    " 

.    40 

7     " 

.     35 

8     " 

.     29 

9    " 

.     22 

10    " 

.     14 

11     •' 

.     14 

12     "           .        . 

.     10 

13     "           .        . 

.      4 

14     "           .        . 

4 

Lasting  15  days 

16  " 

17  " 

18  " 

19  " 

20  " 

21  " 

22  " 

23  " 

24  " 

25  " 

26  " 

Total  . 


5  cas 

4  ' 

3  ' 
1 

2  ' 

3  ' 
0  ' 

0  ' 

1  ' 
0  * 


2t5 


It  will  be  seen  from  the  above  table  that  in  the  largest  number  of 
cases  the  fever  terminated  upon  the  sixih  day  of  the  disease.  In  15S 
cases,  or  60  per  cent.,  the  fever  lasted  from  five  to  nine  days.  It  must 
be  remembered  that  the  prevailing  form  of  the  disease  was  mild  and 
the  mortality  low. 

Jamieson  states  that  of  200  cases  observed  by  him  the  maximum 
temperature  was  reached— in  11  cases  on   the  first  day,  in  76  on  the 


368  SCARLET  FEVER 

second  day,  in  75  on  the  third  day,  in  36  on  the  fourth  day,  and  in  2 
cases  on  the  fifth  day/ 

Deviations  from  the  pyrexial  curve  above  mentioned  not  infrequently 
take  place.  Instead  of  declining  by  lysis  the  temperature  may  fall  by 
crisis.  On  the  third  or  fourth  day  a  sudden  decline  of  the  fever  to 
normal  or  subnormal  may  take  place.  The  temperature  may  then 
continue  for  some  days  at  or  slightly  above  normal.  Henoch,  Fiirbringer, 
and  Jiirgensen  have  described  such  cases  and  Litten  has  reported 
instances  of  high  initial  fever  followed  by  an  apyretic  course.  Henoch 
noted  4  cases  out  of  175  with  normal  morning  temperature  and  evening 
elevation.    Litten  observed  similar  cases. 

Ordinarily,  high  fever  accompanies  severe  cases  with  well-marked 
eruptions,  but  there  are  numerous  exceptions  to  this  rule.  Leichtenstein 
mentions  a  case  with  marked  delirium  and  intense  eruption  running  an 
almost  afebrile  course.  Cases  of  a  malignant  type  may  be  entirely 
unaccompanied  by  elevation  of  temperature,  and,  indeed,  the  temper- 
ature may  even  be  below  the  normal  line. 

It  is  not  rare  for  very  mild  cases  to  be  unaccompanied  by  pyrexia. 
We  recall  an  afebrile  case  developing  in  the  hospital  whose  temperature 
record  we  were  enabled  to  observe  for  several  days  before  the  attack. 

Fiirbringer^  describes  a  secondary  fever  in  scarlatina  that  is  inde- 
pendent of  and  unaccompanied  by  any  discoverable  complication. 

Wunderlich,  quoted  by  Trousseau,  observed  a  considerable  elevation 
of  temperature  during  the  stage  of  desquamation.  Gumprecht  and 
Jiirgensen  have  also  recognized  this  secondary  fever.  Thomas^  describes 
irregular  cases  of  scarlatina  with  protracted  fever.  He  writes:  "When 
the  fever  is  irregular  it  fails  to  defervesce  after  the  normal  progress  and 
disappearance  of  the  eruption  and  angina,  but  continues  for  weeks, 
sometimes  with  the  same  intensity  and  a  typhoid  character  like  that  of 
a  variety  of  scarlet  fever  presently  to  be  described;  sometimes  with 
increasing  intensity,  especially  if  it  is  to  prove  fatal,  and  at  other  times 
it  declines  gradually  as  in  protracted  defervescence.  In  such  cases  the 
pulse  is  often  very  rapid,  the  heart's  action  violent,  and  the  first  sound 
of  the  heart  diffuse  or  even  replaced  by  a  distinct  murmur."  And, 
again,  "Not  infrequently  there  occurs  still  another  form  of  the  disease 
in  which  there  are  not  only  local  affections  of  moderate,  perhaps  even 
trifling  importance,  but  also  disproportionately  severe  fever  of  long 
duration  which  characterizes  this  variety  as  a  typhoid  scarlatina." 
Thomas  remarks  that  in  these  cases  the  fev,er  is  the  chief  symptom  and 
that  it  may  be  protracted  for  weeks. 

Hyperpyrexia  is  more  frequently  observed  in  scarlet  fever  than  in  the 
other  exanthematous  diseases.  It  is  not  so  rare  for  107°  F.  to  be  reached ; 
such  cases  usually  terminate  fatally,  although  when  the  hyperpyrexia 
is  not  protracted  recovery  may  take  place.  In  rare  cases  the  fever  may 
mount  to  an  extraordinary  height.    Wunderlich  records  a  temperature 

1  Quoted  by  Forchheimer,  loc.  cit. 

2  Realeacyklopadie,  Bd.  x.,  5,  p.  472.    Quoted  by  Jiirgensen,  loc.  cit. 

3  Loc.  cit.,  pp.  254  and  269, 


THE  SYMPTOM  A  rOLOav  OF  SCA  RfJ':!'  FEVER  369 

of  110.8°  K.;  Thomas,  111.2°  F.;  I>oiclit(;ii.sl(;in,  100° and  100.0°  F.,  and 
Dr.  Currie,  according  to  (ircgory,  112°F\  These  rises  of  temperature 
were,  as  might  be  expecte(],  shortly  followed  by  death. 

Throat  S'i/mpf<)7ns. — Throat  symptoms  are,  as  has  been  stater),  early 
complained  of  by  adidts.  On  ins})(;ction,  general  fancial  redness  is 
observed,  involving  pjirticnlarly  the  uvnhi,  tonsils,  and  soft  j)ahit(;.  ^^'hen 
the  cutaneous  eruj)tion  begins  to  manifest  itself  the  redness  increases 
and  there  develops  oedema  and  swelling  of  the  mucous  tis.sues.  At  times  a 
thin,  grayish  or  yellowish  film  of  exudate  may  be  seen  on  the  swollen 
tonsils.  Often  the  soft  palate,  uvula,  and  buccal  mucous  membrane 
show  a  punctated  redness  similar  to  that  later  ol^served  ujjoji  the 
skin. 

The  stage  of  invasion  is  brief,  not  lasting  ordinarily  more  than  twenty- 
four  hours.  In  some  cases  the  eruption  appears  before  twelve  hours 
have  elapsed. 

In  a  series  of  84  cases  of  scarlatina,  Barthez  and  Rilliet  observed  the 
eruption  appear  as  the  first  symptom  in  4;  in  the  majority  of  the  cases, 
however,  the  eruption  manifested  itself  at  the  end  of  twenty-four  hours. 
Trousseau  saw  a  severe  case  of  scarlatina  with  marked  brain  symptoms 
in  which  the  rash  was  delayed  until  the  eighth  day.  It  is,  however, 
distinctly  exceptional  for  the  stage  of  invasion  to  last  much  longer  than 
twenty-four  hours. 

Stage  of  Eruption. — The  exanthem  of  scarlet  fever  usually  begins 
upon  the  neck  and  subclavicular  regions,  then  spreading  rapidly  to  the 
chest,  face,  abdomen,  arms,  and  legs.  A  variable  time  elapses  in  different 
cases  before  the  acme  of  the  eruption  is  reached.  The  milder  efflor- 
escences reach  their  height  earlier  than  those  of  greater  intensity.  In 
severe  cases  the  rash  may  take  until  the  third  or  fourth  day  before  its 
greatest  intensity  is  attained. 

The  color  of  the  scarlatina  exanthem  varies  in  different  individuals 
and  is  extremely  difficult  to  depict  in  words.  It  has  been  variously 
designated  by  writers  as  scarlet,  bright  red,  boiled-lobster  tint,  raspberry- 
juice  color,  rose  colored,  wine  colored,  etc.  These  terms  are  permissible 
because  they  convey  a  definite  impression  to  the  mind,  but  when  these 
tints  are  compared  with  the  exanthem  at  the  bedside  the  terms  are  seen 
to  be  inaccurate.  The  color  of  any  inflammatory  eruption  is  due  to  the 
blood  appearing  through  the  texture  of  the  skin.  The  amount  of  blood 
in  the  skin  as  determined  by  the  calibre  of  the  cutaneous  bloodvessels, 
the  character  of  the  blood,  and  the  complexion  of  the  individual  all 
influence  the  coloration.  It  is  a  matter  of  daily  observation  that  the 
rash  in  fair-skinned  persons  is  brighter  than  in  those  of  swarthy  com- 
plexion, whose  skin  contains  a  greater  amount  of  epidermal  pigment. 
In  general,  the  scarlatinal  rash  is  reddish,  sometimes  bright,  but  more 
often  dull  or  dusky  red.  Sometimes  the  eruption  is  so  brownish-red, 
particularly  in  dark-complexioned  individuals,  as  to  almost  approach 
a  bright  terra- cotta  color.  IMore  rarely  the  element  of  blue  is  so  well 
marked,  particularly  in  dependent  areas  of  skin,  as  to  be  quite  purplish 
owing  to  the  venous  congestion.    The  color  varies  not  only  in  different 

24 


370  SCARLET  FEVER 

persons,  but  at  different  periods  in  the  same  individual.  A  bright 
eruption  commonly  becomes  dusky  before  it  fades. 

When  the  scarlatinal  exanthem  is  viewed  at  a  little  distance  it  gives 
the  impression  of  a  uniform  reddish  blush.  When,  however,  the  skin 
is  closely  scrutinized  it  is  seen  that  it  is  made  up  of  innumerable  reddish 
points  or  puncta.  These  are  of  a  deeper  tint  than  the  skin  intervening 
between  them. 

At  tunes  eruptions  are  seen  in  which  the  skin  between  the  puncta  is 
of  normal  coloration.  This  appearance  may  occasionally  be  noted 
during  the  coming  out  or  evolution  of  the  exanthem.  Ordinarily  the 
points  of  greatest  color  intensity  are  surrounded  by  areolae  of  somewhat 
brighter  hue.  When  these  coalesce,  as  is  usually  the  case,  a  diffuse 
eruption  is  presented,  the  puncta  being  scarcely  distinguishable  through 
the  obliteration  of  contrast.  At  times  the  areolae  are  narrower,  exhibiting 
a  little  intervening  normal  skin  and  giving  the  eruption  a  more  or  less 
speckled  appearance.  In  other  cases  with  larger  pale  areas  a  mottled 
appearance  is  noted.  Finally,  there  may  exist  large,  irregular  patches 
of  healthy  skin,  particularly  on  the  arms,  legs,  and  buttocks,  producing 
so  marked  a  blotchiness  of  the  exanthem  as  to  suggest  a  strong  resem- 
blance to  measles. 

The  scarlatinal  eruption  frequently  exhibits  small  pinpo"nt  to  pin- 
head-sized,  reddish  elevations,  which  occur  most  commonly  at  the  sites 
of  hair  follicles.  These  are  frequently  seen  upon  the  extremilies, 
particularly  the  lower,  but  may  also  appear  upon  the  trunk.  This 
condit  on  was  called  by  the  older  writers  scarlatina  papulosa. 

In  addition  to  these  elevations  a  general  goose-flesh  condition  of  the 
sk  n  is  not  infrequently  observed.  This  is  best  marked  upon  the  abdo- 
men and  chest,  and  is  characterized  by  immerous  pinhead-sized  papules 
bearing  a  close  resemblance  to  the  "cutis  anserina"  evoked  in  the 
normal  skin  by  exposure  to  either  extreme  of  temperature.  These 
papules  may  be  faintly  red  or  of  the  normal  skin  hue.  They  differ  from 
ordinary  goose-flesh  in  that  they  persist  usually  for  some  days.  At 
times  this  condition  is  so  pronounced  as  to  impart  to  the  skin  a  "nutmeg- 
grater"  feel  and  appearance. 

In  the  older  descriptions  of  scarlet  fever  one  reads  of  the  occurrence 
of  sudamina  at  the  height  of  the  efflorescence.  Inasmuch  as  during  this 
stage  the  skin  is  hot  and  dry  with  no  tendency  to  sweating,  one  would 
not  expect  to  find  sudaminous  sweat  vesicles.  It  is  extremely  common, 
however,  to  find  in  well  developed  rashes  innumerable  miliary  vesicles. 
To  this  condition  the  term  scarlatina  miliaris  or  scarlatina  vesicularis 
has  been  given.  The  vesicles  are  conical,  epidermal  elevations,  pin- 
point to  pinhead  sized  (size  of  millet-seed),  with  turbid  or  lactescent 
contents,  and  usually  disseminated,  although  occasionally  occurring  in 
groups.  They  are  commonly  situated  on  the  abdomen  and  chest  and 
to  a  lesser  extent  on  the  extremities.  The  region  in  which  they  are 
frequently  most  copiously  present  is  the  mons  veneris,  for  here  the  ery- 
thema is  often  intense.  In  this  region  they  are  prone  to  develop  into 
minute  but  well-marked,  yellowish  pustules. 


Till':  HYMI'TOMATOLOdV  ( )!''  SCA  ItLICT  i'lCVI'lit  ."J] 

Rarely,  f()iiii'i;iioiis  vcisielcs  iiuiy  coalesce,  fonninjj;  hlc^fts  of  the  size  of 
a  ])ea  or  larger,  ccni.stitutiiig  tli(!  .scarlatina  jHnri/ph'Kjoidca  f>f  the  older 
writers. 

Miliary  vesicles  may  be  seen  in  nearly  all  well-pronounced  scarlet- 
fever  eruptions.  They  are  much  more  fref|uent  than  is  generally 
sup])()sed,  l)eing  often  overlooked  on  account  of  their  minute  proportions. 
A  niagiu'fyiiig  glass  will  often  ))riiig  them  into  view  wh(;n  they  are  not 
clearly  perceived  by  the  unaided  eye.  In  perhaps  20  per  cent,  of  all 
cases  and  50  per  cent,  of  well  j)ronounced  eru|)fioiis,  vesicles  are  readily 


Miliary  vesicles  with  lactescent  contents  appearing  about  the  axilla  with  the  rash  of  scarlet  fever. 


visible  if  looked  for;  lesions  of  this  size,  however,  do  not  intrude  them- 
selves upon  one's  vision  upon  cursory  inspection  of  the  rash.  The 
vesicles  are  more  conspicuous  in  severe  eruptions  than  in  mild  rashes. 
In  decidedly  exceptional  instances  they  may  be  so  pronounced  as  to 
overshadow  the  general  scarlatinal  exanthem  and  puzzle  the  physician 
in  the  diagnosis.  Dr.  J.  P.  C.  Griffith,  of  this  city,  has  reported  several 
such  cases. 

Gee,  Squire,  Bohn,  Rilliet  and  Barthez,  D'Espine  and  Picot,  Moizard, 
Baginsky,  Vogel,  and  others  believe  that  miliary  vesicles  are  determined 
by  an  excessive  degree  of  inflammatory  action  of  the  skin.    Thomas,  on 


372  SCARLET  FEVER 

the  other  hand,  thinks  that  the  miHary  vesicles  are  produced  by  a 
pecuhar  disposition  of  the  skin  of  patients.  He  states  that  in  some 
epidemics  this  condition  has  been  noticed  so  often  and  in  such  abundance 
that  the  normal  eruption  was  observed  only  in  a  minority  of  cases. 
Griffith^  fully  coincides  with  the  latter  view.  He  cites  cases  in  which 
extensive  miliary  eruptions  accompanied  mild  scarlatinal  rashes.  He 
feels  that  it  is  perfectly  possible  in  occasional  cases  to  have  the  presence 
of  an  abundant  miliarial  eruption  cause  decided  difficulty  in  the  diagnosis 
and  even  lead  to  error. 

In  a  large  experience  with  scarlet,  fever  we  have  found  miliary  vesicles 
to  be  much  more  frequently  associated  with  intense  rashes  than  with 
mild  eruptions,  although  they  may  occasionally  be  seen  in  the  latter. 

The  older  writers  seemed  to  think  that  this  miliary  eruption  accom- 
panied certain  epidemics  of  scarlatina,  and  they  fancied  that  these 
"miliary  epidemics"  represented  a  peculiar  infection  rather  different 
from  ordinary  scarlet  fever. 

During  the  period  of  the  fading  and  decline  of  the  eruption,  pea-sized 
or  larger,  flat,  epidermal  elevations  are  often  noted.  These  are  whitish 
and  suggest  sudamina  the  contents  of  which  have  been  absorbed,  for 
one  seldom,  if  ever,  discovers  fluid  in  them.  They  may  be  readily 
opened  with  a  needle,  and  resemble  empty  pea-pods.  The  exfoliation 
of  the  summits  of  these  lesions  and  of  the  miliary  vesicles  constitutes 
the  beginning  desquamation  on  the  trunk,  but  this  will  be  later  referred  to. 

The  character  of  the  eruftion  on  the  face  varies  somewhat.  In  some 
cases  this  region  remains  entirely  free.  More  commonly  the  temples  and 
cheeks  are  the  seat  of  a  deep -red  flush;  it  is  probably  that  this  flushing 
is  often  associated  with  the  true  rash,  for  it  is  not  rare  to  see  the  face 
desquamate  profusely.  The  forehead  often  shows  redness,  but  this  is 
usually  less  intense  than  on  the  lateral  aspects  of  the  face.  The  tip  and 
alse  of  the  nose,  and  the  upper  and  lower  lips  and  the  chin,  commonly 
appear  preternaturally  pale.  This  circumoral  pallor  defined  by  the 
marked  flushing  of  the  cheeks  gives  the  patient  a  most  curious  appear- 
ance, which,  if  not  peculiar  to,  is  always  strongly  suggestive  of  scarlet 
fever. 

On  the  arms  and  legs  the  rash  exhibits  no  peculiarities  save  its  likeli- 
hood to  early  involve  the  flexures  of  the  joints  (groins,  popliteal  spaces, 
and  elbow  flexures),  and  its  greater  tendency  to  be  blotchy.  Upon  the 
palms  and  soles  the  eruption  is  usually  diffusely  red  without  any  puncta. 

When  pressure  is  made  upon  the  scarlatinal  rash  a  momentary  pallor 
is  produced,  then  a  return  of  redness  and  flnally  a  gradual  paling  again 
which  persists  for  some  minutes.  We  have  seen  on  the  legs  pale  bands 
persist  where  garters  had  previously  been  worn. 

Indeed,  one  may  inscribe  a  name  upon  the  efllorescence  with  a  blunt 
instrument  and  in  a  few  moments  note  the  white  letters  stand  out  upon 
the  red  background.  This  is  the  reverse  of  the  ordinary  dermographism 
and  might  be  termed  ancemic  dermographism.     This  is  a  vasomotor 

1  Scarlatina  Miliaris,  Jacobi's  Festschrift,  1900,  pp.  182-186. 


77//';  HYMI'TOMATOl/XlY  OF  SnAUL/'/r  /''HVER 


873 


peculiarity,  biii  it  is  douhtful  whether  it  possesses  any  reliable  diagnostic 
value. 

Itching  is  not  infr(H|ij(',ntly  cxpcricnccrl  by  scarlet-fever  patients. 
While  in  most  cases  it  is  insi^nii(i(  ant  or  entirely  absent,  it  is  occasionally 
quite  severe.  It  may  be  noted  during  the  early  evolution  of  the  eruption, 
at  its  height,  or  during  the  decline  just  before  desquamation  sets  in. 

In  intense  eruptions  there  is  often  some  adema  and  swelli7if/  of  the 
skin  accompanied  by  an  exaggeration  of  the  lines  of  cleavage.  The 
skin  under  such  circumstances  is  thickened  and  shows  wrinkling  of  the 
epidermis. 

On  the  other  hand,  the  eruption  may  be  so  mild  as  to  make  the 
diagnosis  difficult  and  even  impossible.  Indeed,  in  rare  cases  the 
eruption  may  l)e  absent  altogether. 


Fig.  fi2 


Ansemic  bands  at  the  sites  of  the  garters  during  the  height  of  a  scarlet-ltx  t-i  ti  upi  i^n,     li.i^  is 
vasomotor  phenomenon  similar  to  the  white  bands  following  digital  stroking. 


The  eruption  persists  at  its  maximum  intensity  but  for  a  brief  period 
— from  a  few  hours  to  a  day  or  two,  and  then  gradually  fades.  ]\Iuch 
variation  is  shown  as  to  the  entire  duration  of  the  exantbem;  ordinarily 
the  eruption  lasts  from  three  to  seven  days,  but  its  life  may  be  shorter  or 
longer  than  this  period.  Cases  doubtless  occur  in  which  the  eruption 
is  of  such  brief  duration  as  to  escape  notice  entirely;  instances  of  scarlet 
fever  without  eruption,  but  followed  by  desquamation,  are  probably  to 
be  accounted  for  by  evanescent  undiscovered  eruptions. 

In  some  cases  a  temporary  fading  or  recession  of  the  rash  occurs.  It  is 
not  rare  for  the  exanthem  to  be  more  vivid  in  color  at  certain  times. 
The  rash  is  not  infrequently  brighter  in  the  evening  than  during  the 
day.  It  is  more  rare  for  the  eruption  to  recede  completely  and  later 
reappear. 

The  Enanthem,  or  Mucous -membrane  Eruption. — As  has  already  been 
stated,  sore  throat  is  not  infrequently  among  the  earliest  of  the  s\Tap- 


374  SCARLET  FEVER 

toms  ushering  in  an  attack  of  scarlet  fever.  In  the  very  beginning 
there  are  commonly  seen  congestion  and  swelling  of  the  tonsils,  uvula, 
and  soft  palate.  A  punctated  redness  is  often  visible  on  the  soft  and 
hard  palate.  During  the  eruptive  stage  the  gums  and  buccal  mucous 
membrane  usually  exhibit  some  redness  and  swelling. 

If  the  gums  are  inspected  from  the  second  to  the  fifth  day  there  will 
oftentimes  be  seen  milk  white  'patches  which  look  much  as  if  they  had 
been  produced  by  the  application  of  pure  carbolic  acid.  These  represent 
a  desquamation  of  the  epithelial  covering  of  the  gingival  mucous  mem- 
brane, and  can  readily  be  peeled  off  by  slight  friction.  This  process 
occurs  at  times  in  measles  and  perhaps  also  in  other  affections  in  which 
there  is  congestion  of  the  oral  mucous  membrane. 

The  tongue  is,  as  a  rule,  heavily  covered  with  a  grayish  fur  at  the 
onset  of  an  attack  of  scarlatina.  Soon  the  tip  and  edges  assume  an 
angry,  reddish  coloration,  and  a  roughened  or  granular  appearance. 

At  this  time  also  the  fungiform  papillae  on  the  dorsal  surface  of  the 
tongue  become  swollen  and  prominent  and  peep  through  the  surface 
coating.  Usually  by  the  fourth  day  or  thereabouts  lingual  desquamation 
takes  place  and  the  coating  is  cast  off,  disclosing  to  view  a  red,  raw- 
looking,  often  glazed  surface  studded  with  enlarged  papillae. 

At  times  the  papillary  elevations  are  numerous  and  small,  looking 
like  the  granulations  in  a  wound.  At  other  times  they  are  scattered  and 
more  prominent.  This  condition  of  the  tongue  is  of  considerable 
diagnostic  importance  and  has  been  variously  described  as  the  "rasp- 
berry," "strawberry,"  or  "cat's  tongue."  It  should  be  remembered, 
however,  that  mild  cases  of  scarlatina  occasionally  exhibit  no  abnor- 
mality of  the  tongue  whatsoever. 

During  the  eruptive  stage  the  condition  of  the  throat  undergoes 
aggravation.  The  tonsils  are  usually  enlarged,  reddened,  and  covered 
with  a  layer  of  mucopus  or  actual  pseudomembrane.  The  uvula, 
anterior  pillars,  and  soft  palate  are  intensely  reddened  and  oedematous. 
The  patient  complains  of  much  pain  in  the  throat,  particularly  on 
swallowing. 

Desquamation. — Exfoliation  of  horny  epithelium  begins  during  the 
decline  of  the  eruptive  stage.  Desquamation  occurs  first  upon  those 
parts  of  the  cutaneous  surface  which  were  first  the  seat  of  the  exanthem. 
(Fig.  63.)  Where  the  face  has  presented  much  eruption  or  even 
intense  flushing  a  branny  desquamation  will  often  be  noted  as  early 
as  the  fourth  day.  Almost  simultaneously  a  similar  epidermal  exfolia- 
tion occurs  upon  the  neck  and  the  upper  portion  of  the  chest.  This 
process  is  commonly  inaugurated  about  the  sixth  or  seventh  day  of  the 
disease. 

If  one  watches  for  the  first  evidence  of  desquamation  on  the  trunk, 
it  will  be  noticed  as  a  number  of  discrete,  pinpoint-sized,  powdery  scales. 
These  represent  the  desiccated  summits  of  the  miliary  vesicles.  In  a 
day  or  two  these  small  scales  are  cast  off,  leaving  minute,  jagged  rings 
of  desquamation.  The  horny  layer  is  now  lifted  off  by  centrifugal 
extension  of  these  rings,  which  grow  progressively  larger.     On  meeting 


Till':  SVMI'TOMATfJLor/Y  OF  HCAULKT  VKVKii 


370 


intestines,  etc.  On  iliis  iiccoiinl  HawU^y  lias  suggested  \\v,\\.  flif;  terin 
lymy)h;i,ti(;  fever  he  siihslitiitefl  I'or  searlet  fever. 

(^iiil(^  early  in  the  conrse  of  searl(;t  ff'ver  do  we  w^Av.  ;in  iif)j)rcfiahle 
ttunefaclion  of  tlu;  suJHMitaneous  lyni[)h  "[hinds,  more  j)!irlinij;irly  those 
sitiuitoul  ahoiit  the  angles  of  the  jaws. 

The  following  presentation  of  the  eondition  of  the  glands  in  100  eases' 
will  give  an  adecpiate  idea  of  tin;  cxicnl  of  (he  lyniphiiOf  iii\olvement 
in  searlet  fever. 

Fk;.  G7 


Pronounced  desquamation  in  large  lamellEe. 

The  various  lymphatic  glands  were  enlarged  in  the  following  pro- 
portion of  cases: 

Inguinal  glands 100  per  ct. 

(a)  pea-sized  ' 23  per  ct. 

(6}  beau-sized 77       " 

Axillary 96 

Maxillary 95 

Posterior  cervical 77 

Anterior  cervical 44 

Submaxillary 36 

Epitrochlear     .        .        .       ' 26 

Sublingual 25 

The  inguinal  glands  were  in  the  main  enlarged  to  the  size  of  a  pea 
or  bean,  although  occasionally  they  would  reach  the  dimensions  of  an 
almond. 

The  epitrochlear  glands  vary  from  the  size  o"  a  lentil  to  a  pea.  Not 
infrequently  the  enlargement  occurred  but  upon  one  side.  Occasionally 
there  is  a  second  enlarged  gland  just  above  the  epitrochlear  gland. 


1  A  Clinical  Study  of  the  Lymphatic  Glands  in  One  Hundred  Cases  of  Scarlet  Fever,  by  J.  F. 
Schamberg,  Annals  of  Gynecology  and  Pediatry,  December,  1899. 


380  SCARLET  FEVER 

The  axillary  glands  vary  in  size  from  a  pea  to  an  almond.  They  are 
usually  enlarged  in  clusters  rather  than  singly. 

The  sublingual  gland  is  scarcely  ever  larger  than  a  lentil  seed.  The 
submaxillary  lymphatic  glands  were  found  to  vary  in  size  from  a  pea 
to  an  almond.  In  one  case  a  gland  reached  the  dimensions  of  an  orange, 
broke  down,  and  suppurated. 

The  maxillary  glands,  or  those  just  behind  the  angle  of  the  jaw,  reach 
the  largest  size  of  any  of  the  lymphatic  glands  and  are  the  commonest 
to  undergo  suppuration.  In  the  above  cases  they  varied  from  the  size 
of  a  bean  to  that  of  an  orange.  The  average  was  perhaps  represented 
by  the  dimensions  of  an  almond  or  hickory  nut. 

The  anterior  cervical  glands,  or  those  lying  in  front  of  the  sternocleido- 
mastoid muscle,  were  usually  pea  to  bean  sized,  as  were  also  those 
posterior  to  the  muscle. 

The  glands  were  examined  at  various  stages  of  the  disease,  as  early 
as  the  second  day,  and  as  late  as  the  fifteenth.  In  the  cases  studied 
upon  the  second  and  third  days  the  glandular  enlargement  was  so  well 
marked  as  to  suggest  the  probability  that  the  glands  are  already  some- 
what tumefied  on  the  first  day  of  the  illness. 

The  duration  of  the  enlargement  doubtless  varies  in  different  patients. 
In  several  cases,  examined  at  intervals  of  a  few  days  for  three  weeks, 
the  glands  were  found  to  gradually  diminish  in  size,  but  at  the  end  of 
this  time  they  were  still  slightly  enlarged. 

Statistics  are  frequently  misleading,  and  those  presented  above  are, 
perhaps,  no  exception  to  the  rule.  While  it  is  true  that  the  inguinal 
glands  were  enlarged  in  every  one  of  the  100  cases  of  scarlet  fever 
examined,  it  is  more  than  probable  that  in  some  of  them  the  enlarge- 
ment antedated  the  attack  of  scarlet  fever.  The  percentage  of  appar- 
ently healthy  children  with  pea-sized  or  larger  inguinal  glands  must  be 
very  considerable.  Still  the  effort  was  made  to  eliminate  this  error  as 
far  as  possible.  It  is  in  most  cases  not  difficult  to  distinguish  between 
an  old  and  a  recently  enlarged  gland.  The  former  has  a  decidedly 
sclerotic  feel,  with  the  resistance,  say,  of  cartilage.  The  latter  presents 
a  peculiar  resiliency  with  the  consistency  of  liver. 

The  enlargement  of  the  glands  about  the  jaw  and  neck  is  ordinarily 
proportionate  to  the  amount  and  intensity  of  throat  involvement.  There 
are,  however,  occasional  exceptions  to  this  rule,  and  it  should  be  recog- 
nized that  extensive  lymphatic  swelling  may  occur  with  but  slight 
throat  symptoms. 

When  the  glandular  swelling  is  of  moderate  extent  and  of  early 
occurrence,  it  usually  undergoes  gradual  subsidence.  When  the  swelling 
is  very  great,  and  particularly  when  it  develops  late,  from  the  second 
to  the  fourth  week  of  the  disease,  it  is  extremely  prone  to  suppurate  and 
form  a  glandular  abscess.  This  will  be  further  referred  to  under  the 
subject  of  complications. 

Respiratory  Symptoms.  Laryngitis. — Despite  the  intense  inflam- 
mation of  the  pharynx  in  scarlatina  there  is  but  little  tendency  to  involve- 
ment of  the  laryngeal  structures.     Trousseau's  epigrammatic  saying, 


77//';  HYMPTOMATOI/XIY  OF  SCARLI'/r  FKVER  381 

"Scarlatiriii  has  no  likitifi;  for  tlic,  hirynx,"  is  hornc  out,  hy  (•x})f'ri('r)ce. 
He  fiiHlier  r(Miiarks:  '"rriio  scarliilinou.s  sorf^  tfiroat,  tlicri,  is  pJiaryn- 
geal,  (lillV'i-iii^f  in  this  respect  from  tlic;  sore  thrfnit  of  measles,  whieh  is 
laryiin-eiti,  and  from  that  of  smallpox,  whieh  is  hofh  [)haryngeal  and 
laryn^ciil." 

It  is  only  when  the  inflammation  of  the  throat  in  scarlatina  is  severe, 
with  tendency  to  f>;}ui/Trenoiis  ehan<i;(;,  and  is  accompanied  by  swelling 
of  the  snrrounding  connective  tissue,  that  tlie  larynx  may  become  com- 
promised. In  such  cases  both  the  mucous  membrane  and  the  connective 
tissue  of  the  larynx  may  undergo  inflammation. 

True,  the  larynx  may  become  involved  later  in  the  course  of  the 
disease  by  the  formation  of  ulcerations  or  the  develo])ment  of  a  pseudo- 
membrane,  which  may  or  may  not  be  due  to  the  diphtheria  bacillus. 

Bronchial  Catarrh.— In  severe  cases  of  scarlet  fever  a  catarrhal  con- 
dition of  the  bronchial  tubes  may  be  present  even  in  the  early  stages  of 
the  disease.  In  malignant  cases,  that  have  proven  fatal  after  an  illness 
only  of  a  few  days,  it  has  not  been  uncommon  on  autopsy  to  find  an 
inflamed  condition  of  the  bronchial  mucous  membrane,  with  the  presence 
of  a  mucopurulent  exudate.  Henoch,^  Jiirgensen,  and  others  have 
recorded  such  cases.  The  former  says:  "The  mucous  membrane  of  the 
bronchi  and  the  parenchyma  of  the  lungs  are  excited  by  inflammatory 
influences  far  more  frequently  than  we  usually  suppose.  Not  only 
catarrh,  but  more  or  less  extensive  bronchopneumonia,  occurs  in  the 
first  and  second  weeks  of  the  disease.  These  conditions  are  frequently 
overlooked,  however,  because  a  whole  series  of  synchronous,  severe 
typhoid  symptoms  disguise  them  and  divert  the  attention  of  the  physician. 
We  found  bronchitis  and  bronchopneumonia  in  nearly  all  the  severe 
cases,  and  also  repeatedly  during  life." 

Pneumonia  either  of  the  catarrhal  or  croupous  variety  is  an  un- 
common occurrence  in  scarlatina;  when  it  does  occur  it  is  usually  in 
connection  with  severe  cases  of  the  disease. 

Leichtenstern  is  authority  for  the  statement  that  "in  children  acute 
lobar  pneumonia,  sometimes  bilateral,  and  mostly  involving  the  upper 
lobes,  appears  as  well  in  the  height  of  the  disease  as  in  the  nephritic 
stage.  These  are  pneumonias  such  as  in  the  shortest  space  of  time  lead 
to  a  complete  infiltration  of  a  whole  upper  lobe,  or  more  rarelv  a  lower 
lobe." 

Gastrointestinal  Symptoms. — Vomiting  occurs  at  the  beginning  of 
the  disease  in  a  large  percentage  of  cases  of  scarlatina.  In  some  severe 
cases  the  vomiting  may  continue  for  some  days  or  may  return  after  it 
has  ceased.  This  may  be  accompanied  by  pains  in  the  epigastrium. 
The  boivels  at  the  onset  of  scarlatina  may  be  normal  or  constipated. 
In  some  cases,  however,  diarrhoea  is  present  and  in  some  instances  it 
may  be  quite  severe.  In  bad  cases  a  persistent  diarrhoea  with  greenish 
or  bloody  stools  is  often  observed.  This  serves  to  increase  the  already 
existing  weakness  and  prostration,  and  therefore  adds  to  the  gravity  of 
the  disease. 

1  Vorlesungen  iiber  Kinderkrankheiten,  p.  642,  third  edition. 


382  SCARLET  FEVER 

The  nasal  mucous  membrane  usually  remains  normal  in  scarlet  fever. 
When  the  nose  is  involved  it  is  usually  the  result  of  extension  of  a 
secondary  infection  from  the  throat.  In  scarlet  fever  of  the  anginose 
form,  the  mucous  membrane  of  the  nose  may  become  reddened,  swollen, 
and  secrete  a  foul,  mucopurulent,  or  bloody  discharge,  which  excoriates 
the  nostrils  and  adjacent  portions  of  the  skin.  Ulceration  of  the  mucous 
membrane  may  occur,  occasioning  the  loss  of  considerable  tissue. 

Severe  involvement  of  the  nose  is  rare  in  simple  scarlatina ;  it  is  much 
more  common  in  the  anginose  variety. 

Roger^  mentions  a  severe  purulent  rhinitis  which  develops  early  in 
some  cases  of  scarlet  fever.  The  profuse  discharge  from  the  nose  is 
accompanied  by  tremendous  swelling  of  the  cervical  glands  and  suppu- 
rative otitis.  Occasionally  extension  of  inflammation  to  the  antrum  or 
the  frontal  sinus  occurs,  as  in  a  fatal  Case  quoted  by  Roger.  The  strepto- 
coccus is  looked  upon  as  the  cause  of  the  purulent  inflammation.  We 
have  not  infrequently  observed  purulent  rhinitis  in  anginose  scarlet  fever. 

The  mucous  membrane  oj  the  lips  is  commonly  swollen  and  reddened. 
The  epithelial  covering  is  often  lost,  leading  to  superficial  ulcerations 
which  are  prone  to  bleed  and  beconie  covered  with  crusts.  The  com- 
missures of  the  mouth  may  be  fissured,  the  rhagades  extending  into  the 
true  skin  and  causing  considerable  pain. 

Scarlatina  Anginosa — Severe  or  Septic  Scarlet  Fever. 

This  form  of  the  disease  is  characterized  by  an  excessive  development 
of  all  of  the  symptoms,  but  with  particular  severity  of  the  throat  man- 
ifestations. The  aggravated  nature  of  the  attack  is  usually  manifest 
from  the  outset.  The  incubative  and  invasive  periods  are  usually 
short;  with  headache,  chilliness  and  vomiting,  the  temperature  rises 
suddenly  to  104°  or  105°  F. ;  with  the  appearance  of  the  eruption,  which 
develops  commonly  within  a  few'  hours  of  the  initial  symptoms,  the 
pyrexia  may  still  increase  until  a  burning  fever  of  106°  or  107°  F.  is 
reached.  The  temperature  in  this  form  is  not  only  higher  than  in 
simple  scarlatina,  but  it  is  also  of  longer  duration.  The  temperature 
during  the  first  five  or  six  days  commonly  fluctuates  between  104°  and 
105°  F.,  and  then  in  cases  that  end  in  recovery  declines  by  slow  gradation 
in  the  course  of  two,  three,  or  four  weeks  to  the  normal  line. 

The  nervous  symptoms  are  pronounced ;  delirium  is  commonly  present, 
alternating  with  periods  of  somnolence  or  semicoma.  At  times  jactita- 
tion with  extreme  restlessness  and  wakefulness  are  noted.  With  children 
there  is  persistent  disposition  to  sleep,  great  irritability  when  awakened, 
and  stubborn  resistance  against  taking  nourishment.  There  is  not 
only  complete  anorexia,  but  also  painful  deglutition  which  prompts  the 
patient  to  reject  the  proffered  food. 

The  rash  is  usually  intense,  covering  the  entire  body,  not  excluding 
the  face.  Indeed,  in  bad  cases  the  face  often  shows  an  intense  deep- 
red,  sharply  marginated,  eruptive  flush  on  the  cheeks,  which  persists 

1  Les  maladies  infectieuses,  p.  346. 


Till':  HYMI'TOMATOLOdY  OF  SCMfLI'/r  FHVIilt 


'JOO 


for  some  days.  'J'lio  eruption  is  of  vivid  fine,  at  times  acfjuiring  even  an 
erysipelatous  a})})earance.  In  other  cases  the  distribution  may  be 
irregular,  the  eruption  occurring  in  patches  upon  the  hands  and  feet, 
flexures  of  joints,  l)uttocks,  legs,  etc. 

In  a  fatal  case  in  a  child  of  eight  months  recently  under  our  care, 
there  Were  fiery-red  patches  on  both  cheeks,  an  intense  erysipelatoid 
rash  on  the  legs,  and  a  faint  punctate  eruption  on  the  trunk. 

The  pulse  is  rapid,  frecjuently  running  between  120  and  150  per 
minute;  it  is  likewise  weak  and  compressible  and  often  arrhytliMiifiil. 


Fig.  08 


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0.  S.,  aged  twenty-five  years.    Woman  with  the  anginose  form  of  scarlet  fever,  treated  at  the 
Municipal  Hospital.    Subsidence  of  temperature  on  the  fifteenth  day.    Recovery. 

The  glands  at  the  angles  of  the  jaw  become  rapidly  swollen;  they 
commonly  attain  the  size  of  a  walnut  or  even  a  small  apple.  The 
surrounding  cellular  tissue  participates  in  the  general  inflammatory- 
process,  producing  great  cervical  intumescence  and  often  causing  the 
child's  head  to  be  bent  backward. 

Upon  inspection  of  the  throat  the  tonsils,  arches,  uvula,  and  soft 
palate  are,  during  the  first  couple  of  days,  seen  to  be  intensely  reddened 
and  oedematous.  Even  at  an  early  date  there  is  a  hypersecretion  of  a 
viscid,  stringy  mucus,  which  adheres  to  the  tonsils  and  soft  palate,  and, 
becoming  dry  as  a  result  of  the  mouth  breathing,  occasions  much 
annoyance  to  the  patient.  Commonly  by  the  third  or  fourth  day  a 
membranous  exudate  appears  upon  the  tonsils,  uvula,  and  soft  palate, 


384  SCARLET  FEVER 

extending  often  to  the  pharynx  and  posterior  nares.  The  occlusion  of 
the  nasal  channels  further  obstructs  the  ingress  of  air  and  distresses  the 
already  harassed  patient.  The  buccal  and  alveolar  mucous  membrane 
is  greatly  congested,  and  often  the  seat  of  ulcerations  from  which  blood 
oozes.  The  teeth,  gums,  and  lips  are  covered  with  sordes,  and  an 
offensive,  at  times  fetid  odor  is  emitted  from  the  mouth.  The  tongue 
is  of  an  angry-red  color  and  occasionally  ulcerations,  covered  with  a 
grayish  exudate,  are  seen  upon  the  edges.  As  has  been  stated,  the  nose 
discharges  a  purulent  material  and  commonly  shows  ulcerations  of  the 
mucous  lining.  The  eyelids  may  also  become  inflamed,  the  conjunctiva 
congested,  and  a  purulent  discharge  issue  from  the  palpebral  cleft. 

The  child  is  often  unable  to  swallow,  water  or  milk  being  ejected 
through  the  nose.  The  nasal  and  faucial  respirations  are  of  a  rattling 
character  and  painful  to  behold. 

The  extension  of  the  morbid  process  along  the  Eustachian  tubes  leads 
to  a  purulent  inflammation  of  the  middle  ear  on  one  or  both  sides. 
Rupture  of  the  tympanic  membrane  occurs  with  the  evacuation  of  the 
purulent  accumulation.  The  external  auditory  canals  become  infected 
by  this  discharge,  and  often  develop  ulcerations  which  may  eat  quite 
deeply  into  the  tissues. 

The  child  with  a  bad  anginose  scarlatina  is  a  pitiable  object — it  lies 
with  the  head  back  to  prevent  the  pressure  of  the  swollen  glands  from 
compromising  the  breathing;  the  neck  is  greatly  tumefied,  the  overlying 
skin  stretched  and  glazed,  the  commissures  of  the  mouth  fissured  and 
covered  with  blood  crusts,  the  nose  discharging  a  sanguinopurulent 
matter,  the  eyelids  swollen,  and  the  ears  expelling  a  thin,  ichorous  pus. 
Indeed,  every  orifice  of  the  face  gives  issue  to  a  putrid  and  foul-smelling 
discharge,  which  contaminates  the  atmosphere  about  the  patient  with 
the  stench.    The  general  symptoms  are  those  of  a  profound  septicaemia. 

In  extremely  bad  cases,  and  in  our  experiences  more  particularly  in 
mixed  cases  of  scarlet  fever  and  diphtheria,  extensive  ulceration  and 
sloughing  of  the  tonsils  or  soft  palate  may  take  place.  The  necrosis  in 
such  instances  involves  the  entire  thickness  of  the  tissues,  and  leads 
commonly  to  perforation  of  the  soft  palate.  We  have  in  a  number  of 
cases  seen  these  perforating  ulcers  of  the  soft  palate;  they  may  be  bilateral, 
or  occur  only  upon  the  one  side.  The  accompanying  symptoms  are  pf 
a  septic  character,  and  the  prognosis  is  unqualifiedly  bad;  death  takes 
place  in  almost  every  case. 

In  fatal  cases  of  anginose  scarlatina  death  may  occur  as  a  result  of 
the  severe  primary  blood  poisoning,  or  through  the  development  of  the 
later  complications,  such  as  nephritis,  pneumonia,  endocarditis,  etc. 

Bronchopneumonia  is  more  frequent  than  is  commonly  believed,  the 
symptoms  being  masked  by  the  severe  angina  and  the  grave  toxaemia. 

The  urine  is  diminished  in  quantity  and  nearly  always  contains 
albumin.  The  microscope  will  often  discover  the  presence  of  tube 
casts  and  also  red  blood  corpuscles. 

A  fatal  termination  is  preceded  by  rise  in  the  temperature  to  106° 
or  107°  F.,  an  increasing  prostration  and  stupor,  and  a  progressive 


77//'.'  HYMPTOMATOI/XIY  OF  SCARfJ'/r  FHVHIt  385 

weakening  and  augmented  frc(|ii(iicy  i)\  I  he  juilsc.  Fatal  cases  usually 
succumb  during  the  first  or  scscond  wc(;k  of  the  illness. 

In  severe  cases  of  angiiiose  scarlatina  the  lym})halic  glands  and 
adjacent  tissues,  under  the  influence  of  intense  inflanimatif)n  or,  y>erfiaps, 
a  special  infection,  may  inulergo  f/anr/rene,  leading  to  gr(;at  sloughing 
and  even  alarming  or  fatal  hemorrhage  from  the  erosion  of  some  large 
bloodvessel.  Trousseau  speaks  of  a  case  in  a  boy  of  fourteen  "  in  whom 
the  gangrene  condition  was  so  extensive  that  tlie  muscles  of  the  neck 
were  dissected,  as  occurs  in  diffuse  phlegmonous  inflammations,  showing 
the  carotids  pulsating  at  the  bottom  of  a  horrible  wound." 

In  cases  that  end  in  recovery  the  temperature  at  about  the  end  of  a 
week  or  ten  days  begins  to  decline,  the  pulse  slows  and  acquires  Ijetter 
volume,  the  marked  nervous  symptoms  gradually  disappear,  and  the 
throat  and  adjacent  cavities  show  a  lessening  in  the  intensity  of  the 
inflammatory  process.  The  decline  in  the  temperature  is  slower  and 
lesS  regular  than  in  the  usual  type  of  the  disease,  and  the  normal  is 
seldom  reached  before  the  end  of  the  third  or  fourth  week.  Con- 
valescence is  apt  to  be  complicated  by  nephritis  and  in  some  cases  by 
rheumatism  and  endocarditis. 

Scarlatina  Maligna. 

Malignant  scarlatina,  a  fortunately  rare  form  nowadays,  is  char- 
acterized by  such  a  sudden  overwhelming  of  the  vital  forces  as  to  cause 
death  in  a  few  days,  or,  indeed,  within  twenty-four  hours.  The  symp- 
toms, consisting  of  extremely  high  fever,  severe  brain  symptoms,  and 
profound  prostration,  with  or  without  hemorrhages  into  the  skin  and 
from  the  mucous  membranes,  develop  with  fearful  rapidity,  and  the 
patient  sinks  under  the  dread  influence  of  the  poison. 

The  abruptness  of  the  onset  of  the  disease  in  these  cases  is  remark- 
able. Children  in  the  enjoyment  of  apparent  perfect  health  may  be 
smitten  while  at  play.  The  child  has  a  severe  attack  of  vomiting,  which 
may  be  accompanied  by  purging,  and  is  followed  by  convulsions  or 
stupor.  The  temperature  rises  rapidly  to  107°  or  108°  F.,  the  pulse  to 
140  or  150.  Great  restlessness  and  delirium  may  alternate  with  stupor. 
Excruciating  headache  and  violent  pains  in  the  extremities  are  some- 
times present. 

The  eruption  is  usually  irregular,  appearing  often  on  the  hands  and 
feet  before  it  is  seen  on  the  body.  At  times  it  appears  only  about  the 
flexures  of  the  joints.  The  rash  may  recede  after  a  brief  presence,  only 
to  appear  a  few  days  later.  It  is  sometimes  partial,  assuming  an  er\'sipe- 
latous  aspect  on  the  face  or  legs.  It  has  commonly  a  h\dd  hue,  being 
beset  with  petechise  and  vibices. 

The  local  symptoms  in  malignant  scarlatina  are  severe.  The  throat 
is  so  intensely  swollen  that  swallowing  is  often  impossible.  The  glands 
are  greatly  enlarged,  and,  if  the  patient  hves  long  enough,  the  nose  and 
middle  ear  become  involved. 

Prostration  and  collapse  may  occur  so  suddenly  that  no  eruption 

25 


386 


SCARLET  FEVER 


appears.  The  skin  is  pale  or  livid,  the  lips  blanched,  the  eyes  glassy 
and  sunken  with  partial  closure  of  the  lids,  the  surface  cold,  the  pulse 
weak  and  fluttering,  and  death  imminent  and  inevitable.  This  choleraic 
type  at  times  cannot  be  diagnosed  without  the  presence  of  other  cases 
of  scarlet  fever  in  the  same  household. 

These  rapidly  fatal  cases  are  rare,  but  well-authenticated  instances 
are  recorded.  Morris^  speaks  of  a  child  that  was  taken  out  apparently 
in  perfect  health  for  its  morning  airing  and  brought  back  within  an  hour 
with  stupor  and  general  muscular  relaxation,  cold  surface,  feeble  pulse, 
and  total  insensibility;  death  occurred  in  twelve  hours.  Within  a  few 
days  two  other  children  in  the  same  family  were  seized  with  scarlet 
fever  which  ran  a  regular  course.  Dr.  Rush  reported  "a  few  instances 
of  adults,  who  walked  about,  and  even  transacted  business,  until  a  few 
hours  before  they  died."    Such  a  case  is  mentioned  by  Morris;  "A  judge 


Fig. 

69 

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W.  R.,  aged  three  years.    Case  of  malignant  scarlet  fever  with  high  temperature,  dying  upon 
the  fifth  day  of  the  disease. 


of  one  of  the  courts  was  seized  with  nausea  while  on  the  bench  and 
retired  to  his  home,  where  for  two  days  he  remained,  scarcely  willing 
to  admit  himself  to  be  sick,  and  reluctant  to  confine  himself  to  his 
chamber,  though  the  rapid,  feeble  pulse  and  an  imperfect  eruption  too 
plainly  indicated  the  nature  of  the  affection;  on  the  third  day  he  died 
while  in  the  act  of  shaving  himself."  A  near  relative  stood  beside  the 
corpse  and  contracted  a  similar  fatal  illness. 

Gregory^  in  referring  to  malignant  cases  says:  "In  some  extreme 
cases  ...  all  the  ordinary  appearances  of  scarlet  fever  are  masked; 
petechise,  coma,  and  a  sloughy  state  of  the  throat  alone  appear."  And 
further  he  remarks  there  are  cases  "where  no  affection  of  the  skin 
takes  place  at  all."  As  an  instance  thereof  he  attended  a  woman  and 
two  grown-up  daughters,  in  all  of  whom  "the  nervous  system  was  utterly 
prostrated,  or  in  the  state  of  collapse.  There  was  no  violence,  no 
delirium,  no  struggling  for  breath,  no  rash;  but  the  pulse  was  small, 


1  Pathology  and  Therapeutics  of  Scarlet  Fever.  Philadelphia,  1858. 


2  Loc.  cit. 


77//';  HVMI'TOMATOLOdY  OF  SCMfLhri'  [''KYHIi.  387 

the  skill  cold,  iuxl  (Ik;  whole;  syslcm  depressed  hy  llu;  inlcnsily  r<f  the 
poison.  .  .  .  'l'li<^-.y  sank  one  iil'icr  t,h(;  other,  withonf,  any  attempt 
to  rally.  It  was  diffieult  to  Relieve  the  disease;  searlatina,  l^nt  the  eldest 
son  took  it  in  tlic  nsnal  form,  recovered,  ;itid  j)iit  (he  matter  beyond 
donht." 

Hemorrhagic  Scarlatina. — Anotiier  form  of  malignant  scarlet  fever 
remains  to  he  described,  namely,  hemorrhagic  s(;arlatina.  This  tyyje  of 
the  disease  is  nshered  in  by  high  fever,  severe  [)rostrati(jn,  and  marked 
brain  symptoms.  A  dusky-red  erythema,  usually  imperfectly  developed, 
is  seen  upon  the  skin  and  is  soon  followed  by  the  appearance  of  scattered 
wine-colored  or  purplish,  ])inhea(l  and  larger  sized  petechia;,  and  later 
ecchymoses.  As  in  hemorrhagic  smallpox,  bleeding  occurs  also  from 
the  various  mucous  membranes,  the  nose,  mouth,  intestines,  kidneys, 
etc.  Epistaxis  and  intestinal  hemorrhages  are  the  most  frequent  and  serve 
to  exhaust  tlie  vitality  of  the  patient.  Vomited  matter  may  show  the 
presence  of  blood  and  thus  early  indicate  the  malignant  character  of  the 
attack.  The  presence  of  blood  in  the  urine  may  result  from  renal 
hemorrhage  or  oozing  lower  down  in  the  urinary  system.  Women  may 
bleed  profusely  from  the  uterus.  If  the  patient  escapes  the  blighting 
influence  of  the  high  fever  and  intense  toxaemia  he  is  pretty  sure  to  be 
prostrated  by  the  hemorrhages  from  the  mucous  membranes,  or  leakage 
into  the  brain  or  the  other  viscera. 

The  condition  of  the  throat  and  lymphatic  glands  is,  in  bad  cases, 
similar  to  what  is  encountered  in  the  anginose  form.  These  cases  are 
almost  invariably  fatal;  the  pulse  becomes  feeble  and  rapid,  the  respira- 
tions quick  and  shallow,  and  the  patient  lapses  into  a  terminal  coma. 

The  occasional  reddish  hemorrhages  into  the  skin  which  accompany 
intense  eruptions  in  well-marked  attacks  of  normal  scarlet  fever,  and 
which  are  particularly  seen  upon  dependent  portions  of  the  body,  such 
as  the  back,  should  not  be  confounded  with  the  malignant  hemorrhagic 
form  just  described. 

Thomas^  calls  attention  to  an  itregular  form  of  scarlet  fever  in  which, 
with  very  moderate  or  trifling  local  symptoms,  there  occurs  a  severe 
protracted  fever.  This  has  been  designated  typhoid  scarlatina,  although 
no  real  connection  with  true  typhoid  fever  is  suggested.  The  protraction 
of  the  fever  for  three,  four,  or  more  weeks  may  be  wholly,  partially,  or 
not  at  all  attributable  to  local  complications.  At  the  outset  there 
are  marked  cerebral  symptoms,  severe  headache,  delirium,  somno- 
lence, and  great  thirst.  The  eruption  comes  out  promptly,  but  is 
often  poorly  developed,  the  same  being  true  of  the  throat  symptoms. 
Desquamation  occurs,  but  the  skin  remains  hot  and  feverish.  Later 
the  patient  becomes  apathetic  and  very  deaf  without  accountable 
ear  trouble;  there  is  enlargement  of  the  spleen,  pulmonary  congestion, 
and  diarrhoea.  Apart  from  the  glandular  enlargement,  there  are  no 
local  complications,  and  one  is  at  a  loss  to  explain  the  remittent  fever, 
which  now  continues  for  weeks.     Nephritis  may  develop  and  cause  a 

1  Loc.  cit. 


388  SCARLET  FEVER 

continued  high  fever,  which  may  sink  to  normal  with  the  subsidence  of 
the  renal  complication.  Typhoid  cases  of  this  character  that  come  to 
autopsy  usually  show — besides  the  usual  scarlatinal  changes — conges- 
tion of  the  meninges  and  brain,  catarrhal  inflammation  of  the  respira- 
tory organs,  hypostases  of  the  lungs,  effusions  into  the  serous  cavities, 
splenic  and  hepatic  enlargement,  swelling  of  the  mesenteric  glands, 
prominence  of  the  follicles  of  the  small  intestines,  and  even  some  tume- 
faction of  Peyer's  patches.  In  some  of  these  cases,  according  to  Thomas, 
a  peculiar  secondary  scarlatinal  eruption  develops  which  differs  from 
the  first  in  that  it  is  not  a  diffuse  erythema,  but  of  the  nature  of  a  roseola. 
The  lesions  are  generally  of  a  dark,  rather  scarlet-red  color,  at  the  same 
time  smaller  and  less  sharply  defined,  generally  closer  together,  and  less 
elevated  above  the  surrounding  pale  skin  than  is  the  case  in  measles. 
The  eruption  may  occur  only  on  the  face  and  extremities,  or  may  be 
copiously  distributed  over  the  body  to  an  extent  even  as  to  render  the 
macules  confluent.  The  rash  may  disappear  in  twenty-four  hours,  or 
may  remain  several  days.  It  is  followed  by  an  intense  lamellar  desqua- 
mation. There  is  a  concomitant  congestion  of  the  throat,  some  renewed 
tumefaction  of  the  glands,  and  the  lingual  papillse  again  become  enlarged. 
Thomas  considers  this  eruption  as  an  irregular  form  of  scarlet  fever, 
and  looks  upon  its  development  in  the  light  of  a  pseudorelapse.  This 
curious  complication  is  not  of  grave  import,  as  most  of  the  patients 
recover. 

Irregular  or  Aberrant  Scarlatina. 

The  symptoms  described  under  the  title  of  scarlatina  simplex  may 
be  considered  as  representing  the  usual  or  normal  manifestations  of 
scarlet  fever.  The  anginose  and  malignant  varieties  are,  in  a  sense, 
deviations  from  the  classical  form,  and,  therefore,  irregular.  In  addition 
there  occur  from  time  to  time,  in  connection  with  the  more  important 
symptoms,  phenomena  which  have  given  rise  to  the  term  irregular 
scarlatina. 

Irregularities  of  the  Fever. — Cases  of  scarlatina  accompanied  by 
extremely  high  temperatures,  reaching  107°,  108°,  110°  F.,  have  already 
been  referred  to.  Such  hyperpyrexia  usually  indicates  malignancy  and 
a  fatal  termination.  The  'protraction  of  the  fever  for  weeks  has  also  been 
mentioned  in  connection  with  the  so-called  typhoid  scarlatina. 

Scarlatina  may,  in  rare  cases,  occur  without  fever  {scarlatina  sine 
febre).  It  is  not  uncommon  to  encounter  very  mild  cases  in  which  the 
temperature,  after  a  brief  and  moderate  rise  for  a  day  or  two,  sinks  to 
the  normal  and  remains  so.  Such  cases  may  present  all  of  the  usual 
symptoms,  but  in  a  very  moderate  form. 

In  a  series  of  cases  reported  by  McCollom,  37  had  temperatures  not 
exceeding  99°  F.  It  has  been  doubted  that  true  scarlatina  occurs 
without  any  rise  of  temperature  whatsoever.  Wunderlich^  expresses 
this  doubt  in  the  following  terms:  "Whether  among  these  abnormally 
mild  cases  there  also  occur  those  in  which  the  temperature  shows  abso- 

1  Das  Verhaltniss  der  Eigenwarme  in  Krankheiten,  Leipzig,  1870,  p.  330. 


Tlll<:  SYMPTOM  A '/'OfJH.'V  OF  SCAia.h'T  FFV/'J/i  389 

lutely  no  change 1  cannot  say  from  my  own  experience, 

because  I  have  never  been  able  in  very  light  cases  to  observe  the  begin- 
ning of  tlie  (lis('ase."  Von  Jiirgensen  mentions  2  cases  in  his  practice 
in  which  there  was  |)riicjiciilly  no  fever.  In  1 ,  in  a  child  of  fhrcf;  and  a 
half  years,  with  a  well-niarkcd  scarlatina,  the  temperature  was  below 
98°  F.  during  the  entire  illness,  with  the  exception  of  one  or  two  occa- 
sions, when  it  momentarily  rose  to  about  100°  ¥.  In  a  second  case 
also  the  tem})eratu)"c  never  rose  above  100°. 

We  have  recently  had  under  our  (;are  a  child  with  scarlatina  which 
developed  in  the  hospital  and  in  which  we  were  enabled  to  watch  the 
temperature  record  for  four  days  preceding  the  attack.  M.  S.,  aged 
nine  years,  was  admitted  to  the  scarlet-fever  ward  of  the  Municipal 
Hospital  from  a  foster  home  in  which  there  was  an  epidemic  of  scar- 
latina. The  patient  had  on  admission  (January  10,  1903)  such  indefinite 
symptoms  as  to  scarcely  permit  the  diagnosis  of  scarlet  fever.  On 
January  14th,  four  days  after  admission,  she  vomited  and  a  well-marked 
scarlatinal  rash  appeared  over  the  entire  body.  At  this  time  her  temper- 
ature registered  99°  F. ;  on  the  15th  and  16th  it  declined  to  normal  and 
then  to  98°;  rising  to  100°  F.  on  the  17th,  and  then  again  falling  to 
normal. 

Irregularities  of  the  Eruption. — The  scarlatinal  eruption  may  depart 
from  its  usual  appearance  and  present  atypical  features.  An  excessive 
development  of  the  miliary  vesicles  to  such  an  extent  as  to  mask  the 
character  of  the  eruption  has  already  been  referred  to. 

Partial  Eruptions. — In  some  very  mild  cases  the  exanthem  may  be 
'poorly  developed  and  limited  to  certain  regions  of  the  body.  The  asso- 
ciated fever  and  angina  are  often  correspondingly  slight.  Gregory  saw 
cases  in  which  the  exanthem  appeared  only  on  the  thighs.  Thomas 
speaks  of  cases  in  which  it  is  limited  to  one  side  of  the  body,  or  the  upper 
or  lower  half  of  the  body,  or  the  lower  extremities.  Glaser  describes  a 
form  in  which  the  exanthem  appears  as  a  broad  band  around  the  neck 
or  around  the  joints.  Wildberg  also  noted  it  in  the  latter  situation. 
Zehnder^  observed  it  in  the  form  of  red  spots  scattered  over  the  body. 

In  exceptional  instances  the  face  may  remain  entirely  free  of  eruption. 
This  is  more  apt  to  occur  in  mild  cases  in  which  the  eruption  is  of  only 
moderate  intensity. 

The  scarlatinal  exanthem  is  sometimes  of  an  intense  hue  and  accom- 
panied by  considerable  swelling  of  the  skin  and  even  subcutaneous 
tissue,  imparting  to  the  condition  an  almost  erysipelatous  appearance. 

Poorly  developed  eruptions  are  not  always  indicative  of  benign 
attacks,  for  the  exanthem  is  sometimes  partial  in  severe  and  even 
malignant  cases  of  scarlatina.  Morris^  says:  "It  is  by  no  means  unusual 
to  meet  with  cases  where  all  the  constitutional  symptoms  are  well 
marked,  though  the  eruption  is  confined  to  the  wrists  or  flexures  of  the 
joints,  and  is  there  limited  to  a  small  number  of  red  poi}its  only.  I  have 
met  with  many  such  in  families  where  other  cases  were  well  marked. 
They  are  frequently  fatal." 

1  Quoted  by  Thomas,  loc.  cit.  2  Loc.  cit. 


390  SCARLET  FEVER 

Malignant  cases  are  often  characterized  by  irregularities  in  the  time 
of  appearance,  duration,  and  character  of  the  eruption.  The  latter  is 
often  blotchy,  like  the  eruption  of  measles ;  in  other  cases  it  is  purplish 
and  at  times  hemorrhagic. 

Scarlatina  Sine  Eruptione,  or  Scarlatina  Sine  Exanthemate. — The 
eruption  of  scarlet  fever  is  its  most  conspicuous  manifestation,  and  is 
commonly  the  symptom  which  leads  to  the  diagnosis  of  the  disease. 
There  is  general  accord  among  writers  on  this  subject  that  scarlet  fever 
may,  in  rare  cases,  occur  without  an  eruption.  In  malignant  scarlatina 
death  sometimes  occurs  so  quickly  that  there  is  scarcely  time  for  the 
exanthem  to  appear.  The  diagnosis  in  such  instances  must  be  con- 
firmed by  etiological  evidence. 

Apart  from  these  cases  the  estimation  of  the  frequency  of  scarlatina 
sine  exanthemate  depends  much  upon  one's  comprehension  as  to  what 
constitutes  scarlatina. 

Nurses  and  physicians  who  are  in  attendance  upon  scarlet-fever 
patients,  and  the  adult  members  of  a  household  in  which  the  disease 
exists,  commonly  contract  a  sore  throat  and  fever.  This  condition  has 
been  termed  angina  scarlatinosa,  or  scarlatina  faucium;  it  presents 
usually  the  same  symptoms  as  are  observed  in  follicular  tonsillitis. 
These  sore  throats  occur  both  in  individuals  who  have  never  had  scar- 
latina and  in  those  who  have  at  some  time  experienced  the  disease. 

To  assume  that  all  of  these  cases  represent  instances  of  scarlatina 
without  eruption  would,  we  feel  sure,  be  unwarranted;  to  assume  that 
they  are  all  non-scarlatinous  would  be,  perhaps,  an  equal  deviation  from 
the  truth.  In  the  present  state  of  our  knowledge  it  is  unwise  to  express 
one's  self  with  any  degree  of  dogmatism  upon  this  question.  The  discovery 
of  the  specific  cause  of  scarlatina  would  shed  a  flood  of  much-needed 
light  upon  these  cases. 

Bohn  conservatively  expresses  himself  as  follows:  "In  the  vicinity  of 
a  scarlet-fever  patient,  febrile  indisposition,  angina,  and  catarrh  of  the 
mucous  membranes,  vomiting,  even  diphtheria  of  the  tonsils,  in  the 
other  members  that  have  already  had  the  disease  are  almost  daily 
occurrences.  We  must  only  accept  a  case  as  one  of  scarlatina,  if,  during 
an  epidemic,  especially  in  families  where  either  early  or  late  a  distinct 
scarlatinal  case  appears,  cases  occur  in  which,  nothing  more  is  lacking 
from  the  fully  developed  picture  than  the  confidently  awaited  exanthem." 

Mayr^  states  that  the  expression  "scarlatina  without  eruption"  is 
only  justified  in  those  cases  in  which  the  exanthem  is  absent,  but  in  which 
we  have  otherwise  typical  attacks  with  fever,  angina,  and  desquamation, 
and  in  addition  etiological  evidence. 

Thomas^  says:  "A  slight  or  moderately  severe  fever  of  short  duration, 
accompanied  by  some  pain  in  the  neck  and  enlargement  of  the  cervical 
glands,  is  not  an  uncommon  occurrence  in  persons  who  have  but  little 
predisposition  to  the  disease,  especially  if  they  be  of  mature  years,  and 
also  in  those  who  have  already  had  scarlet  fever  in  childhood.     These 

1  Scarlatina.    Hebra's  Diseases  of  the  Skin,  English  translation,  London,  186C. 

2  Log.  eit.,  p.  251. 


TIII<]  HYMI'TOMATOIJHIY  OF  SCAU.LMT  F/'JVI'JU  39] 

symptoms  are  the  more  sns|)icioii,s  if  sfjirlct  fever  lias  occurred  in  tlif 
family,  or  if  the  })ati(!iit  lias  j)r()l)jtl)ly  Ik^c.ii  oxf)os('(l  to  the  poison.  If 
the  throat  he  examined,  tlu;  eiia,raet(!risti(;  redn(!ss  is  seen  in  a  mild 
form,  with  or  without  a  moderate  <!nlarfi;ement  of  tin;  tf)nsils;  perhaps 
also  the  tongue  i)resents  the  appearance  of  tlx;  scarlet-fever  tongue. 
There  are  also  malaise,  anorexia,  headache,  and  other  symptoms  of 
slight  importance.  Such  attacks  generally  disappear  in  a  few  days, 
hut  they  should  i-eceive  the  same  attention  which  is  })aid  to  the  unmis- 
takahle  disease.  Every  throat  afjection  diirmg  a  scarlcijever  epidemAc 
is  suspicious." 

That  some  of  these  sore  throats  are  cases  of  true  scarlatina  faucium  is 
evidenced  hy  the  fact  that  genuine  scarlet  fever  is  occasionally  C(m- 
tracted  from  persons  suffering  from  this  variety  of  the  disease.  Morris' 
records  such  a  case:  "The  wife  of  a  medical  friend  of  mine,  who  was 
aiding  in  the  care  of  the  children  of  a  relative,  was  seized  with  this 
modified  affection  and  communicated  scarlet  fever  in  all  its  integrity 
to  her  own  children." 

Graves^  refers  to  a  boy  who  was  taken  home  from  a  school  where 
scarlet  fever  was  prevailing;  he  complained  of  pain  on  swallowing, 
slight  headache,  and  nausea.  The  next  day  the  tonsils  were  swollen  and 
there  was  increased  pain  on  swallowing;  the  pulse  was  sharp,  the  skin 
hot,  but  there  was  no  trace  of  eruption.  These  symptoms  continued 
three  days  and  then  disappeared.  Before  the  boy  had  completely 
recovered,  his  father  and  two  sisters  took  scarlatina. 

Trousseau,  Graves,  and  others  have  reported  cases  occurring  in 
scarlatina  households  in  which  anasarca  without  previous  eruption  has 
been  the  symptom  to  attract  attention  to  the  patient.  Trousseau  remarks : 
"I  came  to  the  conclusion  that  the  persons  who  had  only  had  eruption 
and  consecutive  anasarca,  those  who  had  only  had  anasarca,  and  those 
who  had  only  had  sore  throat,  had  all  had  scarlatina,  the  affections 
seen  in  all  of  them  being  manifestations  of  that  disease." 

Thomas  refers  to  cases  in  which  the  scarlatinal  nature  of  the  disease 
is  proved  by  the  subsequent  occurrence  of  the  characteristic  desquama- 
tion, even  when  there  has  been  no  previous  trace  of  an  eruption.  We 
have  already  spoken  of  a  case  of  a  ward  maid,  in  attendance  upon 
scarlet-fever  patients,  who  developed  sore  throat,  enlarged  glands,  and 
well-marked  desquamation  without  having  had  a  discoverable  rash. 
There  was,  on  close  inspection  on  one  day,  a  faint  flush  over  the  chest, 
but  no  more  redness  than  is  seen  at  times  in  health.  We  believe  that 
all  patients  who  desquamate  characteristically  have  had  an  exanthem. 
Desquamation  is  the  terminal  stage  of  certain  vascular  changes  in  the 
skin,  and  it  is  inconceivable  that  a  patient  should  present  well  marked 
scaling  without  an  antecedent  eruption.  To  be  sure,  the  eruption  may 
be  of  extremely  brief  duration  and  may  entirely  escape  observation. 

Secondary  Septic  Erythema. ^ — Occasionally  in  severe  cases  of  scar- 
latina of   the  anginose  variety,  a  dusky  red,  maculopapular  erj-thema 

1  Loc.  cit.,  p.  35.  -  Quoted  by  TroTisseau. 


392  SCARLET  FEVER 

is  observed  to  occur  in  the  second  or  third  week  of  the  disease.  The 
eruption  is  most  commonly  seen  about  the  extensor  surfaces  of  the 
knees  and  elbows,  although  it  is  at  times  more  extensive  and  may 
involve  the  face  and  a  considerable  portion  of  the  surface  of  the  trunk 
and  extremities.  This  erythema  usually  persists  for  two  or  three  days. 
It  occurs  in  bad  "septic  cases  with  purulent  rhinitis,  sloughing  throat 
and  discharging  ears,  and  is  of  evil  prognostic  import.  The  discharging 
nose  and  blotchy  eruption  may  excite  suspicion  of  a  superadded  measles 
infection. 

Reference  has  already  been  made  to  an  extensive,  secondary,  dark-red, 
roseolous  eruption,  mentioned  by  Thomas  and  regarded  by  him  as  a 
pseudorelapse  rather  than  an  accidental  complication. 

Scarlatina  Without  Angina. — In  many  mild  cases  of  scarlet  fever  the 
congestion  of  the  throat  is  so  slight  that  under  other  conditions  the 
throat  might  not  be  regarded  as  deviating  from  the  normal.  Writers 
generally  agree  that  in  rare  cases  scarlatina  may  exist  without  any 
angina  whatsoever.  In  those  cases  in  which  the  sore  throat  is  absent 
the  eruption  is  usually  poorly  developed,  the  fever  is  very  moderate, 
and  the  entire  attack  mild. 

Berge^  reports  a  series  of  cases  of  puerperal  and  surgical  scarlet  fever 
in  which  there  was  not  the  slightest  involvement  of  the  throat.  He  believes 
that  the  angina  in  scarlatina  represents  the  site  of  inoculation  of  the 
poison,  and  cites  the  above  cases  to  show  that  infection  may  take  place 
through  other  mucous  membranes  or  wounds,  in  which  event  the  angina 
may  be  absent. 

Scarlatina  Without  Desquamation.— As  a  rule,  the  extent  of  the 
desquamation  is  proportionate  to  the  intensity  of  the  eruption  which 
precedes  it.  There  are,  however,  occasional  exceptions  to  this  general- 
ization. Severe  desquamation  may  now  and  then  follow  mild  eruptions, 
and  but  slight  scaling  may  develop  after  a  well-marked  exanthem. 

When  there  has  been  no  discoverable  eruption  there  may  be  no 
desquamation,  and  even  at  times  when  there  has  been  but  a  slight 
eruption  present,  the  desquamation  may  be  so  insignificant  as  scarcely 
to  be  detectable. 

Second  Attacks  of  Scarlatina.— In  the  vast  majority  of  individuals 
one  attack  of  scarlet  fever  will  protect  against  the  disease  for  life.  While 
there  are  many  cases  on  record  of  second  and  a  few  of  third  and  fourth 
attacks,  it  is  quite  obvious  that  in  a  disease  which  so  often  presents 
difficulties  of  diagnosis,  the  estimate  of  the  number  of  cases  reported 
must,  to  a  certain  extent,  be  discounted  to  allow  for  error.  Willan  never 
encountered  an  instance  of  second  attack  among  2000  cases  of  the 
disease  that  he  attended.  On  the  other  hand,  Trojanowsky  estimated 
that  6  per  cent,  of  his  cases  consisted  of  second  attacks.  Thomas,  in 
an  experience  of  many  hundreds  of  cases,  was  able  to  convince  himself 
of  a  second  attack  in  only  a  single  instance.  Henoch,  likewise,  noted 
but  a  single  instance  of  second  attack.  Kinnicutt  saw  two  attacks 
within  eight  months  in  a  boy  five  years  of  age. 

1  Pathogenie  de  la  scarlatine,  Paris,  1895. 


rilF.  HYMI'TOMATOI/KIY  OF  SCAULKT  FEVER  393 

Third  attacks  are  of  excessive  rarity.  Sir  Gilbert  Blane  observed 
three  attjick,s  in  a  yoiin^^  lady  "without  tlic  htast  .suspifion  of  ambiguity 
or  possibility  of  nii.stake  in  (liaj^nosis."  Kicliarflson,  Gill(;.spie,  Murchi- 
son,  Bins,  Moore,  and  TJiom}),son  have  also  reconled  third  attacks. 
Pritchard,  of  Glasgow,  has  reported  the  case  of  a  patient  who  was 
treated  in  the  same  hospital  for  three  attacks  of  scarlet  fever  occurring 
within  two  years. 

Stiebel  writes  as  follows:  "In  the  case  of  a  woman  about  fifty  years 
of  age,  I  have  seen  scarlet  fever  run  its  complete  course  four  years  in 
succession,  the  skin  desquamating  in  certain  areas  in  parchment-like 
pieces  a  half-shoe  in  length."  Von  Jiirgensen,  who  quotes  Stiebel, 
remarks,  "From  the  latter  circumstance  I  take  the  case  to  be  a  genuine 
one." 

To  our  minds  the  regular  periodicity  of  these  attacks  and  the  exfolia- 
tion of  large  sheets  of  epidermis  point  most  strongly  to  the  attacks 
having  been  of  the  nature  of  "erythema  scarlatiniforme"  of  the  exfolia- 
tive type,  and  not  true  scarlatina. 

The  same  statement  applies  to  the  case  reported  by  Jahn  of  a  woman 
who  had  seven  attacks,  and  to  that  of  Henrici  of  a  woman  who  is  said 
to  have  had  sixteen  attacks  of  scarlet  fever. 

As  showing  the  comparative  frequency  of  multiple  attacks  of  the 
infectious  disease,  the  figures  of  Mycelius  quoted  by  Sternberg  are 
interesting : 

Second  Third  Fourth  Total. 

attacks.  attacks.  attacks. 

Smallpox 505  .9  0  514 

Scarlet  fever 29  4  0                      33 

Measles 36  1  0                       37 

Typhoid  fever        ....    202  5  l  208 

Cholera 29  3  2                       34 

From  this  table  it  would  appear  that  multiple  attacks  of  scarlatina 
are  less  common  than  of  the  other  exanthemata. 

Korner,^  who  has  made  a  careful  study  of  scarlatina  recurrences 
came  to  the  conclusion  that  second  attacks  were  rather  more  severe 
than  first  attacks.  He  mentions  8  cases  in  wdiich  the  second  attack 
was  fatal.  The  first  attacks  commonly  occurred  in  childhood  before 
the  age  of  ten,  and  the  second  attack  from  two  to  six  years  later,  although 
in  6  cases  a  second  attack  occurred  within  a  year. 

Recurrent  Eruptions  and  Relapses.— Considerable  confusion  has 
arisen  in  literature  concerning  the  proper  classification  of  secondary 
scarlatinal  eruptions.  It  is  well  knowai  that  the  exanthem  of  scarlet 
fever  may,  in  rare  instances,  disappear  and  recur  in  a  few  days;  it  is 
manifestly  improper  to  regard  the  reappearance  of  the  eruption  under 
such  circumstances  as  a  true  relapse.  Again,  after  complete  con- 
valescence from  scarlatina  the  eruption  of  scarlatina  and  other  sjTnptoms 
may  appear  for  a  second  time.  It  is  somewhat  difficult  to  set  a  definite 
time  limit  before  which  recurrences  are  to  be  regarded  as  relapses  and 
after  which  they  are  to  be  looked  upon  as  second  attacks. 

1  Ueber  Scharlach  recidive.    Jahrbuch  fvir  Kinderheilk.,  1875  aud  1S76,  N.  F.,  ix. 


394  SCARLET  FEVER 

Reasoning  from  analogy  with  the  relapses  of  typhoid  fever,  we 
might  regard  as  a  relapse  in  scarlatina  a  redevelopment  of  several  or 
all  of  the  more  important  symptoms  of  the  disease,  occurring  either 
during  the  course  of  the  illness  itself  or  immediately  after  the  com- 
pletion of  convalescence.  Cases  recurring  some  time  after  convalescence 
has  been  established  ought  to  be  regarded  as  second  attacks. 

Relapses  are,  in  all  likelihood,  due  either  to  a  reawakened  activity 
of  the  scarlet-fever  poison  within  the  body,  or  to  a  reinfection  from 
without.  Kennan^  believes  that  a  patient  with  a  mild  scarlatina  placed 
in  a  ward  with  severe  cases  might  later  be  reinfected.  From  a  study 
of  the  literature  he  thinks  relapses  are  more  common  than  formerly, 
and  attributes  the  increase  to  the  grouping  of  cases  in  special  hospitals. 
True  relapses  usually  occur  during  the  second  or  third  week  of  the 
disease. 

In  the  majority  of  cases  the  recurrence  is  quite  as  complete  in  its 
symptomatology  as  the  original  attack.  Not  only  does  the  eruption 
reappear,  but  there  may  be  also  renewed  fever,  vomiting,  and  sore 
throat.  In  other  cases  the  first  or  the  second  attack  may  be  rudimentary 
and  poorly  developed  and  may  complement  each  other.  The  recurrence 
commonly  runs  a  shorter  and  milder  course  and  usually  ends  favorably; 
that  this  is  not  invariably  so  is  instanced  by  the  statistics  of  Korner, 
who  noted  a  fatal  termination  in  8  cases  of  second  attack. 

Richardson  gives  an  interesting  account  of  a  large  number  of  relapses 
on  board  the  frigate  "Agamemnon."  During  an  outbreak  of  scarlatina 
300  out  of  800  men  were  attacked.  The  ship  was  then  thoroughly  dis- 
infected and  aired  for  a  month.  Of  102  convalescents  who  returned 
to  the  ship,  18  developed  relapses  within  five  days.  The  disease,  how- 
ever, also  recurred  in  many  of  those  who  remained  on  land.  The 
second  attacks  were  in  some  cases  mild,  but  in  others  as  severe  as  the 
original  disease. 

Relapses  developing  immediately  after  scarlatina,  and  second  attacks 
within  four  or  five  weeks,  have  been  reported  by  Bartels,  Barthez  and 
Rihiet,  Faye,  Gaupp,  Jenner,  Hillier,  Kjellberg,  Lefevre,  Miiller,  Hall, 
Peacock,  Richardson,  Robbelen,  Schwarz,  Smith,  Solbrig,  Steinbeck, 
Steinmetz,  Steinhall,  Stiebel,  Trojanowsky,  Wood,  and  others.^ 

Before  accepting  a  secondary  eruption  as  a  true  relapse,  the  possibility 
of  its  being  a  septic  rash  must  be  eliminated.  These  septic  eruptions 
are  often  spotted  in  character,  but  may  at  times  closely  resemble  the 
true  eruption  of  scarlet  fever.  The  roseolous  eruption  associated  with 
protracted  fever,  referred  to  by  Thomas  as  a  pseudorelapse,  is  probably 
of  this  nature. 

In  very  rare  instances  a  second  relapse  may  occur.  Such  a  case  has 
come  under  our  observation,  the  temperature  chart  of  which  is  repro- 
duced (Fig.  70). 

A.  D.,  an  Italian,  aged  twenty-one  years,  was  admitted  to  the  Municipal 
Hospital  on  June  9,  1892,  on  the  fifth  day  of  an  attack  of  scarlet  fever. 

1  Dublin  Journal  of  Medical  Sciences,  1898,  No.  324. 

'■^  Quoted  by  Thomas,  loc.  cit.,  English  translation,  Ziemssen's  Encyclopedia,  p.  190. 


TUN  SYMI'TOMATOI/XIY  Oh'  I^CMNJCT  FI'-.VHIi 


395 


He  had  a  well-marked  rash,  sf)rc  throat,  arxl  \\'\\i\)  U-wr.  The  cvfinin^ 
ternperatun^  on  {hv.  (hiy  ol"  admission  was  105°  F.  (Jn  the  ninth  day 
there  was  well-[)ronounee<l  d(^sc|tianiation.  The  ternj>eratnre  hoverefJ 
between  99°  and  101°  F.  until  the  eif^hteenth  day,  when  it  rose  to  105°  F. 
Accompanying  this  rise  there  were  headache,  abdominal  pain  and 
diarrlux'a,  and  a  recurrent,  very  bright  rash;  no  throat  symptoms. 
Urinary  examinations  were  n(!gative.  'i'lircc;  chiys  hiter  a  second  desqua- 
mation began.  'Vhe  temperature  jk^w  grachially  d(;cl  ned,  reaching 
normal  on  the  twenty-seventh  day  of  the  disease.  The  patient  was 
believed  to  be  well,  when  on  July  6th,  or  the  thirty-second  day  of  the 
disease,  the  temperature  again  rose  to  101|°  F.  The  patient  com- 
plained of  a  sliglit  sore  throat,  and  a  rash,  followed  by  a  fine  desfjuama- 
tion,  appeared  on  the  face,  arms,  and  trunk.  The  tem})erature  declined 
quite  promptly;  the  patient  made  a  good  recovery  and  was  discharged 
from  the  hospital  on  July  26th. 

Fig.  70 


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Scarlet  fever  ;  two  relapses.    A.  D.,  aged  twenty-one  years. 


It  is  seen  that  the  first  relapse  occurred  upon  the  eighteenth  dav  of 
the  disease,  and  the  second  upon  the  thirty-second,  or  just  two  weeks 
later. 

Complications  and  Sequelae  of  Scarlet  Fever. 

Throat.^ — Angina  is  an  essential  feature  of  the  symptomatology  of 
scarlet  fever  and  cannot  be  regarded  as  a  complication  except  where  it 
is  excessively  developed.  The  most  moderate  expression  of  the  scar- 
latinal sore  throat  is  a  uniform  congestion  of  the  uvula,  anterior  pillars, 
and  tonsils.  This  form  has  been  designated  as  erythematous  angina. 
In  more  severe  cases  the  mucous  membrane  is  greatly  swollen,  and  there 
is  extension  of  the  catarrhal  inflammation  posteriorly  to  the  pharvngeal 
wall  and  anter'orly  over  the  soft  palate;  these  parts  are  of  a  deep- 
red  color  and  bathed  in  a  profuse  mucoid  secretion.     The  swelling  of 


396  SCARLET  FEVER 

the  soft  palate  may  be  so  intense  as  to  seriously  interfere  with  swallowing 
and  to  cause  the  regurgitation  of  liquids  through  the  nose,  The  tonsils 
may  also  exhibit  great  increase  in  size  and  embarrass  both  deglutition 
and  respiration. 

In  the  membranous  variety  of  angina  the  mucous  membrane  of  the 
tonsils  is  covered  with  an  exudate,  which  is  usually  of  a  yellowish  or 
brownish  tint  and  thinner  and  softer  than  the  membrane  of  true  diph- 
theria. While  in  most  cases  the  pseudomembranous  deposit  is  limited 
to  the  region  of  the  tonsils,  it  is  not  uncommon  for  it  to  be  present  upon 
the  half- arches  and  also  scattered  in  patches  upon  the  soft  palate.  It 
may  likewise  spread  by  way  of  the  pharynx  into  the  posterior  nares 
and,  in  rare  cases,  to  the  tongue  and  buccal  mucous  membrane.  Exten- 
sion of  the  process  along  the  Eustachian  tube  gives  rise  to  inflammation 
of  the  middle  ear,  a  most  frequent  complication  of  anginose  scarlet  fever. 
The  glands  about  the  angles  of  the  jaw  undergo  inflammation  and 
tumefaction  and  commonly  suppurate.  Pronounced  constitutional 
symptoms  accompany  this  variety  of  the  disease.  The  temperature 
hovers  about  104°  or  105°  F.,  and  there  is  marked  disturbance  of  the 
nervous  system.  Intense  restlessness,  delirium,  stupor,  coma,  or  con- 
vulsions may  be  present.  The  pulse  is  extremely  frequent,  often  reach- 
ing 140  or  150  beats  per  minute.  There  is  profound  prostration,  the 
urine  contains  albumin,  and  the  patient  is  completely  overwhelmed  by 
the  poison  of  the  disease. 

When  there  is  extension  of  the  process  to  the  nose  a  purulent  rhinitis 
is  set  up.  There  is  a  profuse  discharge  of  a  thin  mucopurulent  and 
often  blood-stained  material,  frequently  containing  shreds  of  membrane. 
This  irritating  discharge  inflames  the  nostrils  and  the  upper  lip  and 
gives  rise  to  impetiginous  sores.  The  nose  is  swollen  and  the  nostrils 
obstructed,  causing  considerable  difficulty  in  breathing.  An  offensive 
odor  is  given  off  which  can  be  detected  some  feet  from  the  bedside. 
The  nasal  inflammation  is  attributed  to  the  action  of  the  streptococcus, 
the  extension  of  whose  pernicious  activity  may  give  rise  to  infection  of 
the  nasal  sinuses. 

French  writers  have  called  attention  to  the  bad  prognosis  in  these 
cases  of  early  purulent  coryza.  The  mortality  in  the  Aubervilliers 
Hospital  was  over  50  per  cent.,  and  this  complication  was  feared  more 
than  the  most  malignant  forms  of  angina. 

The  membranous  inflammation  may  extend  to  the  larynx  and  produce 
serious  difficulty  in  respiration.  As  has  already  been  stated,  however, 
laryngeal  involvement  is  extremely  rare  in  scarlet  fever. 

In  normal  scarlatina  the  larynx  is  exempted,  and  the  mucous  mem- 
brane, being  in  a  healthy  state,  is  not  particularly  susceptible  to  the 
noxious  influence  of  the  streptococcus  or  the  diphtheria  organism.  In 
measles,  on  the  other  hand,  the  larynx  is  primarily  involved  and  the 
soil  is  rendered  favorable  for  the  implantation  of  these  micro-organisms. 

The  gangrenous  variety  of  angina  is  fortunately  rare,  and  is,  for  the 
most  part,  observed  in  hospitals.  The  gangrene  may  begin  upon  the 
tonsil,  at  the  site  of  the  rupture  of  an  abscess.     The  necrotic  process 


77//';  (JOM/'fJCATfONS  OF  SCAUfJ'/r  F/CV/af  Pjij-J 

may  involve  the  eiiiiro  ton.sil,  which  .sloughs  out  enmassc.  In  soine  cases 
the  gangrene  is  hinited  to  the  tonsillar  tissues;  in  others  it  spreads 
beyond,  attacking  and  destroying  the  palatine  arches,  the  uvula,  and  a 
considerable  portion  of  the  soft  palate.  The  affected  parts  are  at  first 
covered  with  a  grayish-blac-k,  puhaceous  de[)osit,  which,  when  thrown 
off,  discloses  to  view  frightful  loss  of  tissue.  The  odor  cmitfcd  frf)m 
these  cases  is  foul  and  penetrating.  The  nose  and  ears  are  commonly 
involved  and  give  exit  to  an  ichorous  discharge.  The  glands  of  the  neck 
are  greatly  swollen;  the  constitutional  depression  is  profound.  In  our 
experience  tlie  most  common  form  of  gangrenous  angina  has  been 
characterized  by  circumscribed  necrosis  of  the  soft  parts,  particularly 
the  soft  palate,  leading  to  irregular  or  rounded  perforations  about  a  half- 
inch  in  diameter.  This  condition  may  develop  early,  or  may  be  po.st- 
poned  to  the  second  or  third  week  of  the  disease.  We  have  observ^ed 
this  complication  much  more  often  in  mixed  cases  of  scarlet  fever  and 
diphtheria  than  in  scarlet  fever  alone.  The  prognosis  in  this  circum- 
scribed gangrene  is  very  unfavorable,  although  patients  occasionally 
recover  with  considerable  deformity  of  the  soft  palate. 

In  extremely  rare  cases  gangrene  may  commit  frightful  ravages. 
The  connective  tissue  of  the  neck  may  become  involved,  the  overlying 
skin  destroyed,  and  the  muscles  and  large  bloodvessels  laid  bare.  Where 
the  patient  does  not  die  of  hemorrhage  from  erosion  of  the  carotid 
artery,  jugular  vein,  or  other  large  bloodvessels,  he  is  sure  to  succumb  to 
the  blighting  influence  of  the  septic  poisoning.  Recovery  can  only  take 
place  where  the  gangrene  is  limited  to  small  areas. 

Secondary  Angina  in  Scarlet  Fever. — The  throat  involvement  thus 
far  described  occurs  early  in  scarlatina  and  influences  to  a  considerable 
degree  the  course  that  the  disease  takes. 

A  secondary  angina  may  develop  late  in  the  disease;  indeed,  at  times 
after  convalescence  is  established.  It  is  not  rare  for  the  tonsils  to 
become  the  seat  of  a  severe  inflammation,  increase  greatly  in  size,  and 
after  a  few  days  undergo  suppuration.  The  neighboring  soft  palate 
becomes  reddened  and  greatly  tumefied.  There  is  distressing  pain,  and 
speech  and  swallowing  are  difficult.  W'^e  have  here  the  usual  symptoms 
of  a  suppurative  tonsillitis  or  quinsy.  In  some  cases  the  tonsillitis 
subsides  without  pus  formation.  We  have  observed  these  late  anginas 
in  hospital  wards,  a  circumstance  wdiich  suggests  a  second  infection 
from  without  as  the  cause.  Similar  attacks  of  tonsillitis  have  occurred 
in  ward  maids  and  nurses,  a  fact  which  renders  this  view  all  the  more 
plausible. 

Postscarlatinal  Diphtheria. — Before  the  days  of  bacteriology  all 
cases  of  membranous  angina  were  regarded  as  diphtheria.  It  is  now 
recognized  that  the  membranous  deposit  frequently  seen  in  the  throat 
early  in  the  course  of  scarlatina  is  nearly  always  due  to  the  streptococcus. 
Diphtheria  is,  as  a  rule,  a  complication  of  the  stage  of  convalescence. 

Caiger^  gives  the  date  of  "onset  of  408  cases  of  postscarlatinal  diph- 
theria : 

1  Article  on  Scarlet  Fever  iii  AUbutt's  System  of  Medicine,  p.  161. 


398  SCARLET  FEVER 

Time  of  Onset  of  408  Cases  of  Postscablatinal  Diphtheria  (Caigee.) 

Percentage 
Weeks.  Cases.        of  total  cages. 

One 11  2.69 

Two 36  8.82 

Three  " 55  13.48 

Pour     .        .    ' 77  18.87 

Five 54  13.23 

Six 46  11.27 

Seven 38  9.31 

Eight 27  6.61 

Nine 18  4.41 

Ten 13  3.18 

Eleven         ...........  9  2.20 

Twelve 9  2.20 

Over  twelve 15  3.67 

It  is  seen  from  the  above  figures  that  the  susceptibihty  to  diphtheria 
is  most  pronounced  from  the  third  to  the  sixth  week  of  scarlet  fever. 

Cases  of  postscarlatinal  diphtheria  are  much  more  common  in 
hospital  than  in  private  practice.  In  large  hospital  wards  it  doubtless 
occasionally  happens  that  a  secondary  diphtheria  remains  undetected 
and  exposes  other  patients  to  the  infection.  The  mortality  of  mixed 
cases  of  scarlatina  and  diphtheria  is,  as  would  naturally  be  expected, 
higher  than  that  of  primary  diphtheria. 

There  is  nothing  in  the  clinical  or  pathological  picture  of  postscar- 
latinal diphtheria  to  distinguish  it  from  primary  diphtheria.  It  is 
usually  limited  to  the  tonsils  and  adjacent  half -arches,  although  it 
may  exhibit  greater  extent  and  spread  to  the  posterior  nares  or  to  the 
larynx.  The  thick,  grayish-white  exudate  contrasts  strongly  with  the 
thin,  smeary,  yellowish  or  brownish  deposit  seen  in  the  early  stages  of 
scarlatina.  Paralyses,  such  as  are  seen  after  diphtheria,  are  excessively 
rare  after  scarlet  fever.  This  observation  is  so  well  attested  that  when 
paralysis  occurs  after  scarlatina  there  is  a  reasonable  ground  for  the 
suspicion  that  a  mixed  infection  has  been  present. 

The  diagnosis  will,  in  large  measure,  rest  upon  the  bacteriological 
findings.  The  presence  of  the  Klebs-I.(OefHer  bacillus  in  a  throat  which 
is  the  seat  of  exudate  indicates  the  existence  of  diphtheria. 

Since  the  specificity  of  the  diphtheria  bacillus  has  been  established, 
numerous  examinations  of  scarlatina  throats  have  been  made  to  deter- 
mine the  character  of  the  membranous  angina.  Chabade,"^  of  St. 
Petersburg,  made  cultures  of  214  scarlatinal  throats;  of  these,  98  had  a 
catarrhal  angina,  33  had  a  lacunar  angina  with  a  pseudomembrane 
in  the  tonsillar  crypts,  and  83  had  a  pseudomembranous  angina  involv- 
ing the  tonsils  and  adjacent  soft  tissues. 

In  the  catarrhal  group  no  diphtheria  bacilli  were  found,  but  strepto- 
cocci and,  at  times,  staphylococci  were  present.  In  the  lacunar  anginas 
the  Klebs-Loeffler  bacillus  was  found  twice.  In  the  pseudomembranous 
cases  the  diphtheria  organism  was  found  eleven  times,  thrice  almost  in 
pure  culture,  and  in  eight  cases  associated  with  the  streptococcus. 

1  De  1' Association  de  la  scarlatina  avec  la  diphth(Srie,  La  semaine  m6d.,  1899,  p.  184.     Quoted  by 
Northrupln  von  Jiirgenseu's  article  on  Scarlatina  in  Nothnagel's  Encyclopedia  of  Practical  ^Jledicine, 


77//';  COMI'LldATIOSH  OF  SdAltLHT  I'l'lVhlK  ,'}li9 

Variol  jukI  I  )ev6'  examined  (lie  iliroats  of  525  cases  of  scarlatina. 
Of  this  nuiiilx'r  ()2  liiul  exudate  in  the  tliroat,  'M)  of  whifh  proved  fo  l;e 
true  dij)htlieriii,. 

Garret  and  Waslihourn,''  from  cultures  of  the  tliroat  of  fJOO  patients 
treated  in  the  r.ondon  Fever  Hospital  from  1890  to  J  SOS,  foinid  that 
over  1  per  cent,  showed  Klebs-LoefHer  bacilli  on  admission. 

For  tlu^  |)nst  few  years  we  have  made  cultures  of  all  scarlatina  [)atients 
admitted  into  the  Municipal  Hospital.  The  (;ulturcs  were  made  at  the 
home  of  the  patient,  in  the  ambulance,  or  after  entrance  to  the  ward. 

In  one  series  of  cases,  in  which  cultures  were  made  after  the  admis.sion 
of  the  patients  to  the  ward,  there  were  1G7  negative  results  and  SO  po.si- 
tive,  or  32.85  per  cent. 

In  a  second  series  of  over  500  cases,  in  which  the  cultures  were  taken 
either  at  the  home  of  the  patients  or  immediately  after  their  reception 
into  the  ambulance,  the  results  were  as  follows: 


Negative  cultures 

.      74 

Positive 

cultures         .             26 

.       HS 

.        .      17 

.       77 

.        .      23 

.      65 

"  M  not  recorded)  34 

.      81 

.        .      19 

.      10 

.        .        3 

390 

122 
Percentage,  23.8 

A  further  series  of  500  cases,  some  cultured  before  admission  to  the 
wards  and  some  shortly  after,  gave  the  following  figures: 

Negative  cultures       .       .    87  Positive  cultures  .  .  13 

.84                                   "               "  .  .  16 

.80                                   "               "  .  .  20 

.86                                   "               "  .  .  14 

.80                                     "               "  .  .  20 

417  83 

Percentage,  19.9. 

The  aggregate  of  these  figures  gives  a  total  of  1259  cases,  of  which 
285,  or  29.25  per  cent.,  yielded  positive  cultures.^ 

The  throats  in  many  of  the  positive  cases  showed  merely  evidences 
of  catarrhal  angina.  Subsequent  cultures  in  the  positive  cases  would 
at  times  be  negative,  but  in  not  a  small  number  of  instances  three  or 
four  positive  cultures  were  obtained.  There  were  comparatively  few 
patients  in  whom  the  diagnosis  of  diphtheria  would  have  been  made 
from  the  clinical  appearances. 

The  diphtheria  patients  are  treated  in  a  building  which  is  quite  apart 
from  that  occupied  by  scarlatina  patients.  i\Iixed  cases  are  treated  in 
the  same  building,  but  in  a  distant  wing. 

Ears. — Inflammation  of  the  middle  ear  is,  perhaps,  the  most  com- 
mon complication  of  scarlet  fever. 

1  SoG.  m6d.  des  hop.,  1900,  xvii.  p.  1025  ;  quoted  by  Norttirup,  loc.  cit. 

2  Ann.  de  mtJd.  et  chir.  enfant,  1899,  t.  iii.  ;  quoted  by  Northrup,  loc.  cit. 

s  These  cultures  were  examined  and  reported  upon  by  the  City  Bacteriological  Laboratory,  which 
Is  under  the  supervision  of  Prof.  A,  C,  Abbott,  of  the  University  of  Peunsylvania, 


400 


SCARLET  FEVER 


Its  frequency  varies  with  the  character  of  the  epidemic  and  with  the 
age  of  the  patient.  In  the  anginose  variety  of  scarlatina  middle-ear 
disease  follows  in  almost  every  case.  Some  epidemics  appear  to  be 
characterized ,  by  a  much  smaller  incidence  of  ear  complications  than 
others.  Holt  mentions  the  fact  that  in  an  epidemic  occurring  in  the 
New  York  Infant  Asylum  in  the  spring  and  summer  of  1889,  there  were 
73  cases  of  scarlet  fever  and  not  one  developed  otitis.  In  a  fall  and  winter 
epidemic  in  the  same  institution,  two  years  later,  of  43  cases  of  scarlet 
fever,  20  per  cent,  developed  otitis.  The  frequency  of  otitis  in  different 
epidemics  is  influenced  by  the  degree  of  angina  present,  and  also  to  some 
extent  by  season,  middle-ear  trouble  being  more  prevalent  in  the  colder 
months.  Infants  are  more  liable  to  develop  otitis  media  than  children 
of  more  advanced  years.  This  may  be  due  to  the  relatively  large  size 
of  the  Eustachian  tube  in  infancy. 

Finlayson  states  that  otitis  was  present  in  10  per  cent,  of  4397  cases 
of  scarlet  fever  reported  by  him.  Caiger^  analyzed  4015  cases  of  scar- 
latina, and  determined  that  otitis  media  with  discharge  took  place  in 
11.05  per  cent,  thereof.  Burckhart  reports  this  complication  in  33  per 
cent,  of  cases.  In  attacks  with  severe  throat  involvement  otitis  occurs, 
according  to  Holt,  in  fully  75  per  cent,  of  cases. 

Bader  and  Guinon^  report  33  per  cent,  involvement  in  the  form  of 
mild  or  catarrhal  otitis,  and  purulent  otitis  in  but  4.5  per  cent,  of  cases 
of  scarlatina. 

Middle-ear  disease  results  from  direct  extension  of  inflammation 
from  the  nasopharynx  and  doubtless  through  the  action  of  the  bacteria, 
chiefly  the  streptococcus.  This  complication  may  develop  at  any  time 
during  the  course  of  scarlet  fever,  even  as  late  as  during  convalescence. 
It  is  apt  to  develop  early  in  bad  cases  with  severe  throat  involvement. 
In  18  cases  of  otitis  media  recently  observed  by  us  the  discharge 
appeared  upon  the  following  days: 

Day  of  Scarlet-fever  Illkess  upon  which  Eighteen  Cases  of 
Otitis  Media  Developed. 


1  on  the 

6th  day.                               1  on  the    . 

.    18th  day 

1  "      " 

8th     "                                     2  "      "      . 

.    19th    " 

2  "      " 

9th    ■'                                     1  "      "      . 

.    20th    " 

1  "      " 

10th     "                                     1  ..      <.       . 

.    21st     " 

1  "      " 

nth    "                                     1  "      "      . 

.     22d      " 

1  "      " 

13th     "                                     1  "      "      . 

.    23d     " 

1  "      " 

16th    "                                   1  ..     .<      _ 

.     32d      " 

1  "      " 

17th    "                                   1  <.     »      _ 

.    35th    " 

One  or  both  ears  may  be  affected;  when  both  are  attacked  the  dis- 
charge does  not,  as  a  rule,  appear  simultaneously,  an  interval  of  four 
or  five  days  or  a  week  separating  the  two  attacks. 

When  the  ear  complication  develops  early  in  the  course  of  the  disease, 
while  the  temperature  is  high  and  nervous  manifestations  still  present, 
the  symptoms  thereof  are  apt  to  be  obscured  by  the  general  condition 
of  the  patient.    When  the  otitis  appears^at  a  later  date,  after  the  scar- 


1  Scarlet  Fever,  Allbutt's  System  of  Medicine,  New  York,  1897,  vol.  iii,  p.  150. 
'  See  Moiisard,  Scarlatine,  in  Traits  des  mal,  de  I'enfance,  Paris,  1897,  vol.  i. 


77//';  COMI'IjIdATION'H  OF  .ST.l /,'/./<;  7'  FKVKli  401 

latinal  fever  has  declined,  ils  df-vclopincnf,  is  acicornpanicd  by  a  sharp 
rise  of  tcirij)erature.  The  fever  is  usually  preccicled  hy  pain,  alfhfjugh 
this  symptom  is  extremely  variable. 

Infants  will  often  carry  their  hands  to  their  cars  and  uftcr  shar[) 
shrieks.  \w  some  cases  there  is  eiilar^(;m(Mit  and  tenderness  of  lyiiij)ha.fic 
glands  about  the  (^ar.  The  otitis  may  be  a  simj>lc  caiarrhal  irdlamination, 
or  it  may  be  furulent  or  suppurative.  In  the  formc^r  variety  the  duration 
of  the  affection  is  much  shorter  and  of  a  less  serious  character.  The 
fever,  pain,  and  tenderness  subside  rapidly  after  spontaneous  rupture 
or  incision  of  the  tympanic  meml)rane. 

Purulent  otitis  media  pursues  a  much  more  protracted  course.  A  mucr)- 
purulent  discharge  may  continue  for  weeks  or,  indeed,  the  condition 
may  lapse  into  a  chronic  suppurative  otitis.  The  immediate  dangers 
associated  with  this  condition  are  extension  of  the  purulent  inflammation 
to  the  mastoid  cells  or  meninges  of  the  Ijrain,  the  erosion  of  bloodvessels, 
with  the  production  of  serious  hemorrhages,  and  finally  the  development 
of  septictemia  or  pysemia. 

Cases  are  on  record  in  which  the  erosion  of  large  bloodvessels  has  led 
to  fatal  hemorrhage.  Baader^  reports  the  case  of  a  three-year-old  boy 
suffering  from  a  purulent  otitis  complicating  scarlatina,  who  developed 
on  the  eleventh  day  of  the  disease  a  severe  and  uncontrollable  hemor- 
rhage from  the .  ear  which  caused  death  on  the  third  day.  Autopsy 
disclosed  a  perforation  of  the  posterior  wall  of  the  tympanic  cavity  and 
an  erosion  of  the  lateral  sinus. 

Hessler^  records  a  case  in  which  a  fatal  hemorrhage  resulted  from 
ulceration  of  the  carotid  artery. 

A  similar  case  is  reported  by  Hynes,^  in  which  a  sudden  and  unlooked- 
for  hemorrhage  poured  from  the  right  ear  in  a  four-year-old  child.  The 
child  later  vomited  blood  in  large  quantities  and  died.  It  was  thought 
that  the  bleeding  came  from  the  internal  carotid  artery. 

Hliber*  reports  a  case  of  hemorrhage  from  an  eroded  vessel  which 
caused  a  haematoma  of  the  neck,  the  opening  of  which  resulted  fatally. 
Kennedy  has  reported  three  fatal  cases  of  hemorrhage,  and  ]Moller  and 
West  each  one  instance. 

The  following  case  of  septicaemia  associated  with  purulent  otitis  was 
observed  by  us  in  the  Municipal  Hospital  in  1SS9: 

F.  F.,  a  boy  aged  thirteen  years,  was  admitted  to  the  hospital  on 
February  2d,  with  a  bad  anginose  scarlet  fever.  His  condition  improved 
for  a  week,  the  temperature  reaching  normal.  On  February  10th  the 
patient  had  a  chill  with  a  rise  of  temperature  to  104f  °  F.  On  the  follow- 
ing day  another  chill  and  a  temperature  of  107f  °  F.  The  next  day  the 
temperature  rose  to  107i°  F.  For  a  period  of  ten  days  there  occurred 
the  most  violent  rises  and  falls  of  temperature,  the  extreme  limits  being 
95i°  and  107i°  F.,  an  excursion  of  12  degrees.  Chills  recurred  each  day 
and  on  one  occasion  repeated  vomiting.    The  ear  which  was  discharging 

1  Acute  Verblutung  bei  Scharlach,  Corres.  bl.  f.  Scbweiz.  Aerzte,  1875,  Bd.  v. 

2  Quoted  by  Forchheimer,  loc.  cit  s  Quoted  by  Forchheimer,  loc.  cit . 
■•  Deutsche  Archiv  f.  klia   Med.,  Bd.  viii.  p.  422. 

26 


402 


SCARLET  FEVER 


was  kept  thoroughly  clean  with  a  carbolized  solution.     By  February 
27th  the  patient  had  recovered  sufficiently  to  leave  his  bed  (Fig.  71). 

The  immediate  dangers  of  purulent  otitis  having  been  passed,  there 
remain  severe  structural  changes  which  may  seriously  interfere  with  the 
sense  of  hearing.  There  may  be  partial  or  complete  loss  of  the  tympanic 
membrane  upon  one  or  both  sides ;  occasionally  the  ossicles  are  destroyed 
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Remarkable  excursions  of  temperature  due  to  suppurating  otitis  media.  F.  F.,  aged  tliirteen 
years,  admitted  to  liospital  in  critical  condition :  bad  throat  and  mouth  ;  ears  discharging  on  second 
day  of  disease.    Various  rises  of  temperature  accompanied  by  chills  ;  ultimate  recovery. 


reference  will  be  made  later.  The  labyrinth  may  be  attacked  in  rare 
cases.  Pye,  Phillips/  and  others  have  reported  cases  in  which  laby- 
rinthine structures  were  necrosed  and  discharged  en  masse.  These 
patients  were,  of  course,  left  completely  deaf.  Bezold^  gives  the  results 
of  185  cases  of  scarlatinal  otitis:  "In  30  there  was  entire  destruction  of 
the  membrana  tympani,  with  the  loss  of  one  or  more  bones ;  in  59  the 
perforation  comprised  two-thirds  or  more  of  the  membrane;  in  13  there 
were  smaller  perforations;  in  44  there  were  granulations  or  polypi;  in 


1  Quoted  by  Holt,  loc.  cit. 


2  Quoted  by  Holt,  loc.  cit. 


TIIK  COMPLICATIONS  OF  HCAIfLh'/r  FEVhlli  403 

15  there  was  total  loss  of  liearing  on  one  side,  and  in  0  f»f  the  cases  on 
both  sides;  in  77  of  the  cases  the  hearin^^  distance  U)V  low  voice  was 
less  than  twenty  inches." 

Burckhardt-Merian'  reported  XS  cases  of  ear  corn[)hcations  of  which 
72,  or  84.7  per  cent.,  involved  both  ears.  Of  4'MY.)  cases  of  acrpiircd 
deafness  and  dumbness,  445,  or  10. .'i  per  cent.,  were  due  to  scarlet  fever. 
May,  of  New  York,  has  collected  similar  statistics;  of  5613  cases  of  deaf- 
mutism,  572  were  traceable  to  attacks  of  scarlet  fever. 

Purulent  otitis  may,  in  rare  cases,  give  rise  to  disease  of  the  mastoid 
antrum.  This  may  occur  during  convalescenc;e  from  scarlet  fever  or 
may  develop  after  the  otitis  has  become  chronic.  The  mastoid  region  is 
painful  and  tender  and  acquires  a  characteristic  appearance — the  great 
postauricular  swelling  causing  the  ear  to  stand  out  prominently  from 
the  head.  The  temperature  rises  to  103°  or  104°  F.,  and,  unless  there  is 
operative  interference,  brain  symptoms  may  manifest  themselves.  On 
incision  a  mastoid  abscess  is  found  present.  At  times  a  superficial 
abscess  is  found  in  the  region  of  the  mastoid,  without  actual  involvement 
of  the  mastoid  cells. 

Thrombosis  of  Lateral  Sinus. — Thrombosis  of  the  lateral  sinus  is 
occasionally  encountered  in  cases  in  which  cerebral  abscess  or  meningitis 
subsequently  develops.  The  onset  is  sudden,  with  chills  and  high  and 
irregular  fever. 

Facial  Palsy. — Facial  palsy  is  by  no  means  a  rare  complication  of 
scarlatinal  otitis.  We  have  observed  this  paralysis  in  a  number  of  cases 
of  severe  middle- ear  disease.  It  is  due  to  an  extension  of  inflammation 
from  the  tympanum  to  the  facial  nerve,  where  it  passes  through  the  roof 
of  the  cavity.  The  symptoms  do  not  differ  essentially  from  facial  palsy 
occurring  from  other  causes. 

Abscess  of  the  Brain. — Abscess  of  the  brain  may  result  from  extension 
of  the  suppurative  inflammation  from  the  middle  ear.  The  petro- 
squamous suture  being  patulous  in  children,  an  avenue  of  infection  to 
intracranial  structures  is  readily  offered.  The  periosteum  of  the  tym- 
panum is  continuous  with  the  dura  mater,  and  extension  of  inflammation 
may  occur  along  this  membrane.  In  addition,  the  infection  may  be 
carried  to  the  brain  through  the  medium  of  the  veins. 

Purulent  Meningitis. — Purulent  meningitis  is  an  extremely  serious 
complication  that  may  arise  from  a  suppurative  otitis.  It  may  have  its 
origin  in  thrombosis  of  the  lateral  sinus  or  may  develop  from  necrosis 
of  the  roof  of  the  tympanic  cavity.  There  are  usually  high  fever,  stiffness 
of  the  neck,  retraction  of  the  head,  vomiting,  and,  at  times,  parahiic 
eye  symptoms.  Death  occurs  ordinarily  in  about  a  week.  The  following 
case  will  illustrate  the  symptomatology  of  this  complication: 

W.  J.,  aged  three  years,  was  admitted  to  the  INIunicipal  Hospital  on 
April  9,  1903,  with  a  severe  attack  of  scarlet  fever.  On  the  sixth  day 
of  the  disease  the  right  ear  discharged.  Fever  was  protracted,  the 
temperature  not   touching  normal  until  the  thirtieth  day.      Later  the 

1  Ueber  den  Scharlach  in  seinen  Beziehungen  zum  Gehurorgan  ;  Volkmann"s  Sammlung  klin. 
Vortriige  Chir.,  No.  54. 


404  SCARLET  FEVER 

temperature  rose  as  the  result  of  a  cervical  abscess.  There  was  no 
fever  from  the  forty-fourth  to  the  fifty-fourth  day.  At  this  time  the 
temperature  began  to  rise  and  the  patient  vomited.  He  cried  out  sharply 
upon  being  disturbed.  A  gradually  increasing  stuporous  state  developed. 
The  neck  was  rigid  and  the  head  retracted.  The  pupils  were  equal 
and  reacted  to  light.  The  patient  gradually  lapsed  into  complete  coma. 
The  temperature  rose  to  106f  °  F.  and  the  patient  died  on  the  ninth 
day  of  the  complication  and  the  sixty-fourth  day  of  the  scarlet  fever. 
When  the  skull  was  opened  at  autopsy  a  foul  odor  was  immediately 
noticed.  A  purulent  exudate  was  found  covering  the  entire  base  of  the 
brain,  but  involving  chiefly  the  left  side.  The  pia  mater  under  the 
left  cerebellum  was  infiltrated  with  pus,  and  there  was  free  pus  in  the 
various  fossae.  There  was  no  discoverable  caries  of  the  petrous  portion 
of  the  temporal  bones,  and  on  opening  these  no  pus  could  be  detected. 
Cultures  from  the  purulent  material  demonstrated  the  presence  of  the 
staphylococcus  pyogenes  aureus. 

Complete  Deafness  .^ — Complete  deafness  not  due  to  middle  ear 
disease  occurred  in  a  boy,  aged  five  years,  at  the  Municipal  Hospital, 
during  convalescence  from  a  well-marked  attack  of  scarlet  fever.  The 
patient  had  been  out  of  bed  for  a  number  of  days,  when  he  was  suddenly 
taken  ill  with  high  fever,  vomiting,  heavily  coated  tongue,  and  delirium. 
This  was  shortly  followed  by  pronounced  mental  hebetude;  vomiting 
persisted  for  several  days,  nothing  being  retained  upon  the  stomach. 
Mental  dulness  continued  for  several  days,  after  which,  upon  the  clearing 
up  of  the  mental  faculties,  it  was  noticed  that  the  patient  was  absolutely 
deaf.  There  had  not  been  any  discharge  from  the  ears  nor  any  other 
evidence  of  otitis.  The  mastoid  region  was  normal.  The  temperature 
for  a  week  or  ten  days  was  markedly  irregular,  fluctuating  rapidly 
between  99°  and  104°  F.  About  the  same  time  that  deafness  was  noted 
there  was  a  paralytic  strabismus.  The  patient  left  the  hospital  absolutely 
deaf.  The  internal  ear  was  doubtless  diseased  in  this  case,  perhaps  as 
the  result  of  a  localized  meningitis. 

Eyes. — In  cases  of  severe  scarlet  fever,  particularly  where  there  is 
a  purulent  rhinitis,  extension  of  the  inflammation  may  take  place  and 
a  severe  conjunctivitis  set  up.  More  often  the  conjunctivitis  that 
develops  is  of  a  mild  character,  with  injection  of  the  bloodvessels  of 
the  sclera  and  lids,  increased  lacrymation  and  photophobia. 

The  lacrymal  duct  and  gland  may  become  involved  through  the 
infection  that  has  its  origin  in  a  purulent  coryza.  Through  this  channel 
other  ocular  structures  may  subsequently  be  attacked. 

Primary  Keratitis. — Primary  keratitis  with  its  unfortunate  train  of 
symptoms  develops  at  times,  particularly  in  scrofulous  subjects.  We 
recall  a  corneal  ulcer  in  a  colored  child,  who  had  previously  suffered 
from  keratitis,  in  whom  perforation  with  prolapse  of  the  iris  occurred. 
Leichtenstern  reports  2  cases  of  corneal  ulcer  and  1  of  hypopyon  keratitis 
occurring  in  a  severe  epidemic  in  the  hospital  at  Cologne.  Thomas 
quotes  Schroter  as  saying  that  the  cornea  may  be  affected  primarily 
and  independently,  usually  in  the  way  of  rapidly  progressing  abscesses 


Till']  aOMI'LldATIONS  OF  SCA/ifJ'JT  FJ-JVJ'J/i  405 

or  suppurating  ulcers  or  pernicious  keratomalacia,  in  wliicli  tfie  cornea 
of  one  or  both  eyes,  witliout  any  marked  symptoms,  hecfjmes  turl^id  in 
a  few  (lays,  is  transformed  in  its  totality  info  a  turhid,  dirty,  grayish- 
white  membrane,  and  exfoliates  piecemeal.  The  inflammatory  |)rocess 
may  travel  thence  over  the  uveal  tract  and  cause  a  panophthal- 
mitis. 

Choroiditis. — Choroiditis  may,  in  rare  cases,  com[)licate  scarlet  fever. 
In  the  epidemic  already  alluded  to  TiCiclitenstern  saw  a  case  of  choroiditis 
which  ended  in  phthisis  bulbi. 

In  those  cases  in  which  a  severe  nephritis  is  present  ophthalmoscopic 
examination  may  reveal  the  existence  of  an  alhuminuric  retinitis.  Both 
eyes  are  usually  equally  and  simultaneously  affecterl.  After  a  protracted 
course  more  or  less  complete  restoration  usually  results. 

Temporary  blindness,  or  amblyopia,  may  complicate  the  kidney  con- 
dition; after  some  days  complete  visijDn  is  usually  restored.  We  have 
personally  observed  such  cases.  Porter'  saw  a  young  girl  with  severe 
complications,  develop  temporary  blindness  with  exophthalmos  from 
infiltration  of  the  cellular  tissue  of  the  orbit.  DuvaP  saw  a  similar 
case  of  exophthalmos  lasting  ten  days,  the  sight  being  subsequently 
fully  restored. 

Within  the  past  few  years  we  have  observed  in  the  Municipal  Hospital 
two  cases  of  orbital  cellulitis  complicating  scarlet  fever  and  leading  to  a 
fatal  termination.  These  cases  were  seen  and  studied  by  Dr.  Burton 
K.  Chance,^  Assistant  Surgeon  to  the  Wills  Eye  Hospital,  Philadelphia, 
to  whom  we  are  indebted  for  careful  notes  of  the  cases: 

Case  I.  was  a  boy,  aged  seventeen  years,  who  during  a  protracted 
convalescence  from  a  severe  scarlet  fever  developed  a  sudden  diffuse 
cellulitis  of  the  right  orbit.  A  chill  and  sharp  rise  of  temperature  were 
followed  by  an  effusion  of  fluid  into  the  areolar  tissue,  with  protrusion 
of  the  globe.  The  eyelids  were  red  and  excessively  oedematous.  The 
fundus  was  at  first  pale,  but  later  intensely  red,  with  fine  hemorrhages. 
There  was  marked  swelling  of  the  disk,  an  overdistention  of  the  veins, 
and  contraction  of  the  arteries.  A  day  or  two  before  death  the  cornea 
became  necrotic  and  the  eye  was  lost.  High  fever,  delirium,  and  coma 
preceded  death,  which  took  place  one  week  after  the  development  of 
the  complication.  The  examination  of  the  orbital  structures  after  death 
revealed  only  a  diffuse  serous  infiltration;  there  was  no  evidence  of 
intraocular  suppuration. 

Case  II.  was  a  boy,  aged  ten  years,  who  was  convalescing  from 
scarlet  fever,  when  there  developed  in  the  right  orbit  an  acute  congestion 
with  infiltration  of  the  tissues,  producing  proptosis  between  the  intensely 
oedematous  lids.  The  local  symptoms  were  similar  to  those  in  the  first 
case.  Throughout  the  course  of  the  process  the  cornea  remained 
unaffected.  Deep  incisions  were  made  into  the  periocular  tissues, 
evacuating  a  quantity  of  blood-tinged  serum,  but  no  pus.  On  the  eighth 

1  Quoted  by  Thomas.  2  Quoted  by  Thomas. 

3  Dr.  Chance  reported  his  findings  in  a  paper  read  before  the  Philadelphia  County  Medical  Society, 
May  27,  ]903.    This  was  published  in  American  Medicine,  June  13, 1903,  p.  960. 


406  SCARLET  FEVER 

day  after  the  onset  of  the  complication  the  patient  was  seized  with  con- 
vulsions and  died.     Permission  to  make  an  autopsy  was  refused. 

In  rare  cases  failure  of  vision  may  be  due  to  atrophy  of  the  optic 
nerve  or  to  detachment  of  the  retina.  O'ptic  neuritis  may  occur  with 
meningitis  or  without  such  involvement,  as  in  a  case  reported  by  Putnam. 

Heart. — The  heart  may  suffer  in  scarlet  fever  from  (1)  the  scarlatinal 
toxin,  (2)  as  a  result  of  nephritis,  and  (3)  from  secondary  infections, 
such  as  rheumatism,  pyaemia,  etc. 

That  the  scarlatinal  poison  has  a  direct  influence  upon  the  heart  is 
seen  in  the  early  tachycardia,  the  heart  beats  being  out  of  all  proportion 
to  the  temperature.  Furthermore,  in  mahgnant  cases  that  are  over- 
whelmed at  the  onset  by  the  poison  of  the  disease,  the  symptoms  are 
those  of  an  acute  cardiac  failure;  the  pulse  is  rapid,  small,  and  irregular; 
the  extremities  are  cold,  and  pallor  and  cyanosis  are  often  present.  In 
severe  cases  of  the  disease,  the  scarlatinal  toxin,  according  to  Romberg,^ 
may  early  cause  a  pronounced  dilatation  of  the  heart. 

The  occurrence  of  nephritis  in  scarlet  fever  naturally  leads  to  changes 
in  the  cardiac  muscle.  Whenever  the  kidney  involvement  is  at  all 
pronounced  there  will  be  found  a  hypertrophy  and  dilatation  of  the  heart. 
The  changes  are  apt  to  be  present  upon  both  sides,  but  the  preponderant 
enlargement  is  nearly  always  found  upon  the  left  side. 

RiegeP  states  that  in  most,  if  not  in  all,  cases  of  scarlatinal  nephritis 
there  is  an  increased  arterial  tension  from  the  very  beginning.  After 
the  blood  pressure  has  persisted  for  some  time,  the  heart  enlarges  as 
a  consequence.  In  some  cases  the  increased  size  of  the  heart  may  be 
noticed  a  few  days  after  the  onset  of  the  nephritis.  It  is  readily  seen 
how  this  form  of  cardiac  disease  is  produced.  The  development  of 
nephritis  by  raising  the  arterial  tension  throws  an  extra  burden  upon 
the  heart;  if  the  heart  has  already  been  injured  by  the  influence  of  the 
scarlatinal  poison,  the  strain  may  be  too  much  and  acute  dilatation  may 
result.  If  the  heart  muscle  has  more  recuperative  power  a  compensatory 
hypertrophy  may  take  place. 

If  the  left  heart  develops  a  pronounced  insufficiency,  a  dilatation  of 
the  right  side  will  usually  occur.  When  this  results  we  see  the  usual 
symptoms  of  cardiac  insufficiency — dyspnoea,  rapid  pulse,  enlargement 
of  the  liver,  etc.  A  murmur  may  or  may  not  be  heard  over  the  mitral 
orifice.  It  is  important  to  recognize  the  fact  that  the  bruit  is  not  due 
to  an  endocarditis,  but  to  cardiac  dilatation.  This  murmur  will  be 
found  to  disappear  as  the  heart  improves. 

Myocarditis. ^ — ^Myocarditis  is  the  heart  condition  which  is  most 
frequently  called  into  existence  by  the  scarlatinal  toxin  and  by  the 
associated  nephritis.  The  other  forms  of  heart  disease  are  more 
commonly  associated  with  secondary  rheumatism  or  septic  infection. 
Ashby  found  endocarditis  not   uncommon  with  rheumatoid   affections 

1  Ueber  die  Erkrankungen  des  Herzmuskels  bei  Typhus  Abdominalis,  Scharlach,  etc.,  Deutsch. 
Archiv  f.  klin.  Med.,  Bd.  xlviii.  p.  369,  and  Bd.  xlix.  p.  413. 

2  Ueber  die  Veriinderungeu  des  Herzens,  etc.,  bei  Acuter  Nephritis,  Zeitschr.  f.  klin.  Med.,  1884, 
Bd.  vii.  p.  260  ;  quoted  by  von  Jurgensen,  loc.  cit. 


TffM  aOMf'fJdATfO.MS  OF  SCARLET  FEVER  407 

devcloj)inf(  in  the  third  or  fourth  week  of  scarlet  fever,  hut  not  witli  tlie 
early  synovitis. 

Roger^  has  found  endocarditis  an  uncommon  complication.  Out  of 
2213  cases  of  scarlet  fever  (1727  in  adults)  examined  by  him,  he  saw 
but  2  cases  of  endocarditis.  On  the  other  hand,  he  noted  extracardial 
murmurs  002  times. 

McCollom,^  in  an  analysis  of  1000  cases  of  scarlet  fever,  says:  "A 
mitral  systolic  murmur  was  detected  in  187  cases;  bruit  de  (jatop  in  5 
cases;  irrcfj^nlar  action  of  the  heart  in  54  cases;  endocarditis  in  '>  and 
pericarditis  in  5  cases."  Many  of  the  murmurs  referred  to  were  thought 
to  be  due  to  lack  of  tonicity  of  the  heart  muscle  as  a  result  of  the  action 
of  the  scarlatinal  poison. 

Von  Jiirgensen  expresses  the  opinion  that  endocarditis  of  the  cardiac 
wall  is  more  common  in  scarlet  fever  than  valvular  involvement.  He 
further  believes  that  tliis  mural  endocarditis  may  slowly  extend  to  the 
valves  after  the  attack  of  scarlet  fever  is  over. 

Pericarditis. — Pericarditis  occurs  from  time  to  time  in  the  course  of 
scarlet  fever,  being  much  more  common  in  association  with  nephritis, 
synovitis,  and  pyemia  than  with  cases  of  simple  scarlatina.  Roger 
has  observed  cases  of  dry  pericarditis,  both  at  the  height  of  the  disease 
and  during  convalescence. 

In  pyaemia  endocarditis  and  pericarditis  are  commonly  present;  the 
exudate  in  the  latter  affection  in  such  cases  may  be  purulent.  Roger 
saw  a  child,  aged  eight  years,  with  a  severe  scarlet  fever  complicated 
by  a  purulent  otitis  media,  die  on  the  forty-seventh  day  of  the  disease. 
At  autopsy  the  pericardium  was  covered  with  a  false  membrane;  there 
was  an  ulcerative  endocarditis  and  an  abscess  in  the  wall  of  the  left 
ventricle.    The  streptococcus  was  recovered  from  these  lesions. 

In  our  own  experience  severe  cases  of  endocarditis  have  been  rare, 
and,  w^hen  present,  have  been  accompanied  by  joint  involvement.  We 
recall  a  twelve-year-old  boy  who  during  the  third  week  of  scarlet  fever 
had  articular  swellings  which  recurred  from  time  to  time  for  several 
weeks.  He  also  had  a  well-marked  albuminuria.  This  patient  developed 
at  a  later  period  an  endocarditis  which  severely  damaged  the  mitral 
valve;  he  subsequently  exhibited  a  presystolic  murmur  with  a  pro- 
nounced thrill  over  the  mitral  region.  The  murmur  had  a  peculiar 
crowing  sound  of  a  musical  character.  After  undue  exertion  he  devel- 
oped a  sudden  dilatation  of  the  heart  with  rapid  pulse  and  a  change 
in  the  character  of  the  murmur  which  now  became  blowing.  He  was 
tided  over  this  crisis,  but  a  few  weeks  later  he  again  developed  a  cardiac 
dilatation  and  died.  A  rather  unusual  symptom  in  this  patient  was  a 
geographic  erythema  which  appeared  over  the  trunk  from  time  to  time, 
recurring  apparently  with  fresh  joint  involvement  and  then  gradually 
fading  away. 

In  another  fatal  case  we  observed  a  vegetative  endocarditis  attack- 
ing the  mitral  and  aortic  valves,  associated  with  pleurisy,  joint  swelUngs, 
and  extensive  purpura. 

1  Loc.  cit.,  p.  941.  '  Scarlatina,  Medical  and  Surgical  Reports,  Boston  City  Hospital,  1899. 


408 


SCARLET  FEVER 


Lymphatic  Glands. — A  generalized  enlargement  of  the  lymph  glands 
constitutes  a  part  of  the  normal  symptomatology  of  scarlet  fever.  The 
subcutaneous  lymph  nodes  in  all  parts  of  the  body  undergo  some  hyper- 
plasia, but  those  situated  in  the  neighborhood  of  the  facial  orifices 
undergo  the  greatest  tumefaction.  That  this  primary  lymphatic  involve- 
ment is  due  to  the  scarlatinal  toxin  is  evidenced  by  the  fact  that  the 
lymphoid  elements  of  the  spleen,  liver,  and  intestines  become  likewise 
hyperplastic. 

It  is  only  when  the  lymph  glands  become  excessively  enlarged  or 
undergo  suppuration  that  a  complication  is  added  that  augments  the 
danger  of  the  disease. 

The  most  aggravated  cases  of  lymphadenitis  occur  in  association  with 
the  anginose  variety  of  scarlet  fever. 


Greatly  swollen  and  suppurating  maxillary  glands. 

In  these  cases  the  glands  at  the  angle  of  the  jaw  undergo  rapid  enlarge- 
ment, causing  the  head  to  be  thrown  backward.  This  complication 
increases  the  suffering  and  danger  of  the  child,  who  by  this  time  is 
already  prostrated  by  the  poison  from  a  sloughy  throat  and  discharging 
ears  and  nose.  The  temperature  is  high,  the  nervous  system  markedly 
disturbed,  and  death  imminent. 

By  the  fifth  or  sixth  day  of  the  disease  the  maxillary  glands  may 
already  have  attained  the  size  of  small  apples.  They  are  hard  at  first, 
but  gradually  break  down  and  suppurate. 

In  cases  of  scarlet  fever  of  less  severity,  but  accompanied  by  pro- 
nounced angina,  it  is  not  at  all  rare  for  the  glands  at  the  angle  of  the 


THE  (!(>MrfJC'A7'ff)NS  OF  SCAUfJ'/J'  F/'JV/<JU.  400 

jaw  to  enlarge  and  .su|)|)nr)t,le.  In  cases  terrninaling  favorably  the 
gland  after  incision  l^econies  gradually  drained  of  pus  in  the  course  of 
a  few  weeks  and  heals  up.  One  or  both  glands  may  suppurate,  the 
process  being  simultaneously  bilatc^ral  in  the  bad  cases.  It  is  rare  for 
any  other  glands  to  undergo  sup[)uration  early  in  the  course  of  the 
disease,  save  in  the  malignant  cases  presently  to  be  describerl. 

The  connective  tissue  of  the  neck  may,  in  large  part,  become  the  seat 
of  a  difjufie  cellulitis  which  develops  during  the  first  or  second  week 
in  connection  with  great  glandular  intumescence  in  severe  cases.  This 
frightful  condition,  known  as  Ludwig's  angina  (Anrjina  Ludovici),  is 
fortunately  rare,  for  it  is  almost  inevitably  fatal.  The  neck  is  diffusely 
swollen,  often  from  the  clavicles  to  the  chin  and  parotid  region;  instead 
of  the  natural  concavity  of  this  region  the  induration  makes  of  the 
curve  a  straight  line. 

The  head  is  forced  back  by  this  extensive  brawny  infiltration.  The 
neck  is  hard,  indeed  often  board-like  to  the  touch,  and  of  a  bluish-red 
color.  There  may  be  great  difficulty  in  breathing,  owing  to  the  unnatural 
position  of  the  head  and  pressure  upon  the  larynx.  The  constitutional 
symptoms  accompanying  this  condition  are. those  of  a  profound  septi- 
caemia; the  fever  is  high  and  irregular,  and  often  associated  with  chills 
and  sweats.  The  pulse  is  rapid  and  feeble,  and  the  prostration  great. 
Death  may  occur  before  suppuration  of  the  infiltration  takes  place.  In 
other  cases  suppuration  occurs,  with  extensive  destruction  of  tissue.  A 
fatal  result  may  occur  from  pressure  upon  the  air  passages  or  from 
oedema  of  the  glottis.  In  other  cases  extensive  burrowing  of  pus  may 
take  place,  the  purulent  fluid  finding  its  way  into  the  thorax,  as  in  the 
cases  reported  by  Henoch  and  Bartels.  Cremen^  saw  the  pharjmx 
perforated,  the  food  coming  out  through  the  opening. 

One  of  the  most  dangerous  consequences  of  the  extensive  suppuration 
is  erosion  of  the  large  veins  of  the  neck.  Baader  reports  two  cases  of  fatal 
hemorrhages  after  extensive  suppurating  cellulitis.  The  first  occurred 
in  a  four-year-old  boy,  during  the  fourth  week  of  a  scarlet  fever  compli- 
cated by  pharyngeal  diphtheria.  A  huge  swelling  extended  from  the 
jaw-bone  to  the  larynx  on  the  left  side.  This  w^as  incised  to  relieve 
suffocative  symptoms.  Instead  of  pus  blood  clots  were  removed,  after 
which  a  thick  stream  of  arterial  blood  issued  forth,  which  was  checked 
by  compression.  Four  days  later  a  fatal  hemorrhage  occurred  from 
the  nose  and  mouth.  The  autopsy  showed  that  the  external  carotid 
artery  had  been  destroyed  by  gangrene. 

In  the  second  case,  a  six-year-old  child  developed  Ludwig's  angina 
on  the  thirteenth  day  of  scarlet  fever.  This  was  incised  below  the 
clavicle;  profuse  hemorrhage  later  occurred  from  this  wound.  Autopsy 
showed  a  large  opening  in  the  external  jugular  vein,  where  it  had  been 
eroded  by  the  suppurative  process. 

A  form  of  late  glandular  involvcmeiit  is  not  uncommon  in  the  course 
of  scarlet  fever.    This  takes  place  after  the  fever  and  acute  S}Tiiptoms 

1  Quoted  by  Thomas. 


410  SCARLET  FEVER 

have  subsided,  not  infrequently  occurring  during  convalescence.  The 
glands  at  the  angle  of  the  jaw  and  the  submaxillary  lymphatic  gland  are 
those  usually  affected.  There  is  moderate  enlargement  of  the  gland, 
which  becomes  quite  hard  and  somewhat  tender.  Suppuration  may 
occur,  but  more  commonly  the  gland  gradually  decreases  in  size  and 
resumes  its  normal  dimensions. 

Retropharyngeal  Abscess.- — Retropharyngeal  abscess  may  occur  as 
the  result  of  the  burrowing  of  pus  from  suppurating  glands.  Bokai^ 
observed  this  complication  seven  times  in  664  cases  of  scarlet  fever  in 
children.  In  6  of  these  cases  the  abscess  was  attributed  to  an  adenitis 
of  the  retropharyngeal  glands.  In  a  fatal  case  this  complication  was 
seen  as  early  as  the  fifth  day  of  the  disease. 

Kidneys. — No  exanthematous  disease  is  so  frequently  complicated 
by  inflammation  of  the  kidneys  as  scarlet  fever.  It  is  rare  for  a  severe 
attack  of  this  disease  to  run  its  course  without  the  development  of 
albuminuria.  The  frequency  of  renal  complications  varies  very  greatly 
in  different  epidemics ;  at  one  time  albuminuria  with  dropsy  is  a  striking 
feature  of  the  prevaihng  type  of  the  disease,  while  in  other  epidemics  it 
is  rare  to  observe  this  complication.  In  general  terms  it  may  be  stated 
that  severe  epidemics  of  scarlatina  are  more  apt  to  be  accompanied  by 
nephritis  than  the  mild  ones. 

Divergent  opinions  have  been  expressed  from  time  to  time  as  to  the 
cause  of  the  scarlatinal  nephritis.  Steiner  claimed  that  nephritis  was 
a  part  of  the  symptomatology  of  the  disease,  just  as  much,  indeed,  as 
the  rash  was.  Most  writers,  while  not  subscribing  to  so  radical  an 
opinion,  regard  the  kidney  involvement  as  due  to  the  scarlatinal  poison, 
whatever  that  may  be.  The  great  frequency  of  this  complication  in 
scarlet  fever  and  certain  peculiarities  in  the  clinical  picture  have  led 
some  writers  to  regard  the  nephritis  as  a  specific  entity  peculiar  to  this 
disease.  It  is  true  that  the  clinical  course  presents  features  which,  to 
a  certain  extent,  differentiate  nephritis  in  scarlet  fever  from  this  affection 
occurring  under  other  circumstances.  The  great  tendency  to  anasarca, 
which  is  particularly  evident  in  certain  epidemics,  the  onset  of  the 
complication  at  a  rather  uniform  period,  and  the  favorable  outcome 
in  cases  presenting  most  alarming  symptoms,  give  to  scarlatinal  nephritis 
a  rather  characteristic  clinical  picture.  Moreover,  the  pathological 
changes  are  of  a  quite  uniform  character,  the  essential  condition  being 
an  acute  glomerulonephritis. 

Forchheimer  pertinently  remarks,  however,  that  almost  identical 
changes  may  be  produced  in  the  kidney  by  the  administration  of  toxic 
doses  of  cantharidin.  It  must  also  be  remembered  that  many  acute 
infectious  diseases  are  complicated  by  the  development  of  nephritis, 
and  this  is  particularly  true  of  those  maladies  in  which  we  have  a 
secondary  infection  with  streptococci;  for  instance,  in  smallpox.  In  a 
careful  analysis  of  the  urine  of  128  cases  of  smallpox,  we  found  albumin- 
uria in  65  per  cent,  and  tube  casts  in  45  per  cent,  of  the  cases.    How 

1  Jahrbuch  f.  Kinderheilk. ,  N.  P.,  Bd.  x.  p.  108  ;  quoted  by  von  Jiirgensen,  loc.  cit. 


rill<:  COMl'hICATIONH  OF  SCAIiLHT  F /'J V K h:  411 

far  the  streptococcus  may  he  held  aecountable  for  flic  iiifl;iimiiatir)ii  of 
the  kidneys  in  scarlatina  is  a  matter  (lifficijlt  to  solve.  Most  writers 
concede  to  this  cause  a  certain  percenta<^e  of  the  renal  corn{)lications. 
The  finding  of  streptococci  in  the  kidneys  at  autopsy  does  not  of  necessity 
convict  these  micro-organisms  of  producing  tlie  nephritis.  With  the 
discovery  of  the  causa  causans  of  scarlet  fever  there  will  doubtless  come 
a  more  satisfying  elucidation  of  the  etiology  of  the  associated  nephritis. 

Albuminuria  may  appear  early  in  the  course  of  scarlatina;  that  is, 
during  the  first  week  of  the  disease.  This  albuminuria  is  usually 
transient,  not  lasting  more  than  one  or  possibly  two  days.  It,  moreover, 
seldom  gives  rise  to  any  definite  symptoms.  Inasmuch  as  it  is  usually 
coincident  with  higli  fever,  it  is  regarded  as  a  febrile  alhnTninuria. 

It  should  be  remembered,  however,  that  this  albuminuria  is  not 
merely  functional,  but  is  due  to  an  acute  degeneration  of  the  tubules 
of  the  kidney,  the  resuU,  doubtless,  of  the  elimination  of  toxins. 

Some  authors  refer  to  an  early  suppression  of  the  urine;  when  this 
occurs  it  is  nearly  always  a  manifestation  of  severe  nervous  disturbance. 

The  nephritis  that  occurs  early  does  not,  as  a  rule,  give  rise  to  ursemic 
symptoms,  nor  does  it  lead  of  itself  to  a  fatal  termination.  In  severe 
cases  of  scarlet  fever  that  terminate  early  in  death,  structural  alterations 
may  be  found  in  the  kidneys,  in  common  with  the  changes  in  the  liver, 
spleen,  heart,  and  other  organs. 

Postscarlatinal  Nephritis,  or  Nephritis  of  Convalescence. — It  is  after 
the  subsidence  of  the  acute  symptoms  that  the  true  scarlatinal  nephritis 
is  prone  to  develop.  Most  of  the  cases  wall  be  found  to  begin  during 
the  third  week  of  the  disease.  We  have  seen  albuminuria  appear  for 
the  first  time  as  late  as  the  sixty-third  day,  and  it  may  even  develop 
at  a  later  period. 

Below  is  appended  a  series  of  61  cases  of  albuminuria  recently  obser^-ed 
among  150  cases  of  scarlet  fever: 


412 


SCARLET  FEVER 


Albuminuria  in  Scarlet  Fever;  Day  upon  which  Sixty-one  Cases  of 
Albuminuria  were  First  Noticed. 


First 

First 

Case. 

noticed. 

Case. 

noticed. 

1. 

3d  day. 

Transient. 

32. 

17th  day.  Lasted  twenty-three  days 

2. 

4th     " 

" 

33. 

17th    " 

Lasted  four  days. 

3. 

4th    " 

" 

34. 

17th    " 

Transient. 

4. 

5th    " 

" 

35. 

19th    " 

Lasted  nine  days. 

5. 

6th    " 

" 

36. 

19th    " 

Lasted  twenty-one  days. 

6. 

6th    " 

" 

37. 

19th    " 

Transient. 

7. 

7th    " 

'■ 

38. 

19th    " 

Persisted. 

8 

7th    " 

" 

39. 

20th    " 

Transient. 

9. 

7th    " 

' '      Reappeared  on  25th  day. 

40. 

20th    " 

Lasted  eighteen  days. 

10. 

8th    " 

" 

41. 

21st     " 

Transient. 

11. 

8th    " 

" 

42. 

21st     " 

" 

12. 

8th    " 

" 

43. 

2l8t       " 

Lasted  seventeen  days. 

13. 

8th    " 

" 

44. 

22d      " 

Transient. 

14. 

9th    " 

" 

45. 

22d      ' 

" 

15. 

10th    " 

" 

46. 

23d      " 

" 

16. 

10th    " 

" 

47. 

23d      " 

" 

17. 

10th    " 

" 

48. 

23d      " 

Lasted  seventeen  days. 

18. 

10th    " 

" 

49. 

25th    '• 

Persisted. 

19. 

11th    " 

" 

50. 

28th     ' 

Transient. 

20. 

11th    " 

" 

51. 

28th     " 

" 

21. 

12th    " 

" 

52. 

29th     " 

" 

22. 

12th    " 

Lasted  eight  days. 

53. 

32d      ' 

" 

23. 

13th    " 

Transient. 

54. 

33d      ' 

" 

24. 

14th    " 

" 

55. 

34th    ' 

" 

25. 

14th    " 

" 

56. 

36th    ' 

" 

26. 

14th    " 

" 

57. 

36th     ' 

" 

27. 

14th    " 

" 

58. 

37th     " 

Lasted  six  days. 

28. 

14th    " 

At  intervals  until  fifty-sixth  day. 

59. 

39th     " 

Transient. 

29. 

15th    " 

Lasted  ten  days. 

60. 

41st      ' 

" 

30. 

16th    " 

Lasted  fifteen  days. 

61. 

63d      " 

Lasted  six  days. 

31. 

17th    " 

Transient. 

It  will  be  seen  upon  reference  to  the  above  table  that  almost  all  of 
the  cases  of  albuminuria  observed  during  the  first  two  weeks  of  the 
disease  were  transient,  lasting  but  a  day  or  two.  In  many  of  the  early 
cases  but  a  trace  of  albumin  was  found.  None  of  the  patients  in  this 
series  had  anasarca  or  any  severe  ursemic  symptoms.  It  is  proper  to 
add  that  these  cases  occurred  at  a  time  when  the  type  of  scarlet  fever 
was  quite  mild. 

x4.s  has  already  been  stated,  the  frequency  of  nephritis  varies  strikingly 
in  different  epidemics.  Roger  gives  an  interesting  analysis  of  the 
occurrence  of  albuminuria  in  2157  cases  of  scarlet  fever  in  adults  and 
children. 

Men.         Women.  Children. 

718  '         1009  430 

16  23  14 

264  308  91 


Number  of  patients 

Fatal  cases  (with  albuminuria) 

Patients  cured  (having  had  albuminuria) 


Total  number  of  cases  of  albuminuria 
Frequency  of  albuminuria  per  100  patients 
"  "  "    100  cured 


380 

331 

105 

38.9 

33.1 

24 

37.6 

31.2 

21 

It  will  be  seen  from  these  figures  that  albuminuria  is  less  frequent 
in  children  than  in  adults. 

Vogl  reports  as  high  an  incidence  of  nephritis  in  one  epidemic  as 
34  per  cent.    Cadet  de  Gassicourt  has  observed  late  nephritis  in  30  per 


Tllli  COMI'UaATIONH  Oh'  SCAUJJ'JT  F/<JVI'J/i  413 

cent,  of  all  cases.  It  was  present  in  IS  per  cent,  in  a  series  of  cases 
studied  by  Fricdliindcr.  Ba^insky  lias  recently  njported  88  cases  of 
nephritis  aiiioti^^  919  cases  of  scarlet  fever  (a  percentage  of  9.57)  observer] 
in  the  hospital  diiriiif^  a  ])eriod  of  five  years. 

Ashby  states  that  the  average  of  several  yc^ars  in  hospital  ca.scs  under 
his  observation  was  6  per  cent.  In  a  series  of  2078  cases  Caiger  reports 
acute  ne[)hritis  in  only  3.32  per  cent.  The  wide  discrepancy  in  these 
figures  may  l)e  due,  to  some  extent,  to  the  standards  adopted  in  inter- 
preting the  presence  of  nephritis,  but  wide  variations  are  not  uncommon 
in  different  epidemics.  Holt  states  that  the  average  is  from  0  to  10 
per  cent. 

Age. — Hetzka,  of  St.  Petersburg,  has  compiled  statistics  of  188  cases 
of  nephritis  occurring  in  children  in  the  Elizabeth  Hospital;  these 
figures  indicate  that  children  under  two  years  of  age  are  very  much 
less  apt  to  develop  nephritis  than  those  above  the  age  of  two  or  three. 

Nephritis. 

Under     1  year        ...     25  cases.  1  case 4    x>er  ct. 

Between  1  and  2  years    .       .  107     "  5  cases 4.6       " 

"        2    "     3      "       .        .  106     "  12      " 11.3 

"        3     "     4      "        .        .      79     "  IC       " 20.2        " 

"        4     "     5      "        .        .      80      '•  20      " 23.2 

"        5     "     0      "        .        .      89      "  18      " 21.9 

After  6     "        .        .  300     "  60      "  ....        .  16.6 

While  severe  cases  of  scarlet  fever  are  more  apt  to  be  followed  by 
nephritis  than  mild  cases,  it  is  impossible  in  any  individual  instance 
to  prophesy  the  development  or  the  non-occurrence  of  this  complication, 
because  the  scarlatinal  attack  may  be  severe  or  mild.  There  appears 
to  be  something  in  the  individual  make-up  which  predisposes  one 
toward  or  protects  one  against  a  complicating  nephritis.  Doubtless 
each  individual  has  certain  organs  or  tissues  whi^ch  are  more  vulnerable 
to  the  noxious  influence  of  the  scarlatinal  poison  than  others. 

The  opinion  formerly  held,  that  "catching  cold"  plays  any  important 
role  in  the  etiology  of  nephritis  complicating  scarlatina,  is  being  dis- 
credited by  most  writers  on  the  subject. 

Symptoms  of  Nephritis. — In  some  patients  albumin  appears  in 
the  urine  for  the  first  time  during  convalescence ;  in  other  cases  albumin- 
uria is  a  reawakening  of  the  nephritic  process  that  manifested  itself 
early  during  the  acute  stage  of  the  disease. 

The  nephritis  with  its  accompanying  symptoms  of  intoxication 
ordinarily  comes  on  insidiously,  although  in  some  instances  it  may 
explode  with  alarming  suddenness.  The  development  of  albuminuria 
is  accompanied,  or  often  preceded,  by  a  rise  of  temperature.  A  febrile 
elevation  in  the  third  week  of  scarlet  fever  will  commonly  be  found  to 
be  due  to  nephritis.  The  character  and  duration  of  the  fever  are 
extremely  variable.  It  may  persist  for  a  number  of  days  or  may  drop 
to  normal  at  the  end  of  forty-eight  or  seventy-two  hours.  The  tem- 
perature often  exhibits  striking  irregularities,  dropping  to  normal  and 
suddenly  rising  again.  Ordinarily  the  pyrexia  is  moderate  in  intensity, 
but  it  may  rise  to  great  height.    We  have  seen  a  temperature  of  106f  °  F. 


414 


SCARLET  FEVER 


accompanying  a  moderate  albuminuria  which  appeared  on  the  twenty- 
third  day  of  the  disease  and  disappeared  on  the  twenty-sixth  day  (Fig. 
73).  In  severe  nephritis  fever  may  persist  throughout  the  duration  of 
this  compHcation.     In  some  cases  no  fever  is  noted  whatsoever. 

Before  the  appearance  of  the  albumin,  there  is  not  infrequently  noted 
a  considerable  increase  in  the  quantity  of  the  urine  voided.  As  a  result 
of  this  polyuria  urination  is  frequent  and  may  wake  the  patient  from 
his  sleep  at  night. 

Most  writers  refer  to  pain  in  the  back  as  one  of  the  early  symptoms 
of  scarlatinal  nephritis;  this  lumbar  pain  cannot  be  frequent  or  severe, 
at  least  in  children,  for  it  is  most  rare  to  hear  a  complaint  in  reference 
thereto.  Haematuria  may  be  one  of  the  early  symptoms  to  direct  atten- 
tion to  the  kidneys. 


Fig.  73 


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Scarlet  fever.   F.  O.,  aged  six  years.  Chart  showing  pronounced  rise  of  temperature  coincident 
with  the  onset  of  albuminuria.    Albumin  was  first  found  on  the  twenty-third  day. 


One  of  the  most  characteristic  features  of  scarlatinal  nephritis  is  the 
marked  pallor  of  the  countenance,  with  puffiness  of  the  eyelids.  In  walk- 
ing through  a  scarlet-fever  ward  one  may  frequently  pick  out  the 
nephritic  patients  by  noting  this  appearance.  GEdema  is  a  particularly 
common  symptom  in  scarlatinal  nephritis.  A  peculiarity  of  this  com- 
plication is  the  tendency  to  rapid  anasarca.  This  appears  to  be  much 
more  common  in  the  nephritis  of  scarlatina  than  in  ordinary  Bright's 
disease.  In  explanation  of  this  it  is  stated  that  the  oedema  is  due  not 
alone  to  the  condition  of  the  kidneys,  but  also  to  changes  in  the  lymphatics 
and  bloodvessels  of  the  skin. 

The  anasarca  is  accompanied  by  a  pale  or  alabaster-like  appearance 
of  the  skin.  The  swelhng  usually  begins  about  the  eyelids  and  the 
ankles,  but  later  the  legs,  genitalia,  and  lower  portion  of  the  abdomen 
become  affected.  In  severe  cases  the  entire  body  may  be  attacked. 
A  thin  and  poorly  nourished  child  may  become  rapidly  metamorphosed 


TIII<:  C()M/'fJCATfON,S  OF  SCAUfJ'JT  h'EVHIt  41  5 

into  a  plump  child  within  a  few  hours,  as  a  result  of  the  axlematous 
infiltration.  Anasarca,  according  to  Troijsscau,  is  met  with  in  cases 
of  medium  severity,  rather  than  those  of  the  most  serious  forms  of 
scarlatina.  Its  frc(|U(nicy  varies  !^vv;\\\y  in  difrcrent  epidemics.  Barthez 
and  llilliet  observed  anasarca  in  one-fifth  of  their  (;ases.  Some  writers 
have  stated  that  nearly  all  of  their  cases  were  dropsical.  Among  the 
150  cases  of  scarlet  fever  referred  to  above,  we  did  not  see  a  single 
instance  of  anasarca,  although  UMlema  of  the  face  was  not  an  uncommon 
symptom. 

Anasarca  may  affect  deej)  seated  structures  or  the  serous  cavities. 
The  fluid  may  hll  up  the  peritoneal  cavity,  giving  rise  to  a  pronounced 
ascites,  or  the  pleural  or  pericardial  sacs  may  be  similarly  infiltrated. 
The  soft  palate,  uvula,  epiglottis  and  arytenoepiglottidean  ligaments 
are  more  rarely  attacked,  in  the  latter  case  giving  rise  to  o'dema  of  the 
glottis.  In  such  cases  intubation  or  tracheotomy  may  have  to  be  per- 
formed to  prevent  suffocation. 

(Edema  of  the  lungs  and  brain  are  extremely  apt  to  be  present  in 
cases  that  terminate  unfavorably. 

Anasarca  may  be  present  in  rare  cases  without  all)umin  being  found 
in  the  urine.  This  does  not  indicate  that  nephritis  is  not  present,  for 
ursemic  symptoms  may  burst  forth  suddenly  and  with  great  intensity. 

Henoch  reports  the  case  of  a  twelve-year  old  child  admitted  to  the 
hospital  with  oedema  of  the  face  and  scrotum  following  scarlet  fever. 
The  urine  was  scanty,  but  contained  neither  albumin  nor  nephritic 
elements.  Two  days  later  convulsions  occurred  and  three  days  after- 
ward the  child  died. 

The  Condition  of  the  Urine. — In  the  so-called  febrile  albuminuria, 
the  urine  contains  albumin  for  a  day  or  two,  after  which  it  disappears, 
perhaps  to  reappear  at  the  end  of  the  third  week.  Microscopic  exami- 
nation reveals  the  presence  of  cylindroids  and  occasionally  a  few  hyaline 
or  epithelial  casts.  Not  infrequently  red  and  white  blood  corpuscles 
are  present.  A  cloudiness  is  often  seen  in  the  urine,  which  is  due  to 
the  presence  of  mucus  resulting  from  the  presence  of  degenerated 
epithelium.  With  the  advent  of  the  true  scarlatinal  nephritis  the  urine, 
as  a  rule,  begins  to  decrease  in  quantity,  although  exceptionally  there 
may  be  for  a  short  time  an  increased  secretion.  The  urine  becomes 
quite  concentrated  and  contains  an  abundance  of  urates,  which  give 
a  pronounced  ring  with  the  nitric  acid  test.  Albumin  is  found  at  first 
in  small  quantity,  but  later  in  larger  amount.  In  bad  cases  it  may 
constitute  half  by  bulk  with  the  heat  test  or,  indeed,  there  may  be 
complete  coagulation  of  the  urine.  At  this  time  hemorrhage  from  the 
parenchyma  of  the  kidney  may  take  place,  causing  the  urine  to  look 
brownish-red  and  smoky.  Under  the  microscope  will  be  seen  red 
blood  corpuscles,  cylindroids,  epithelial  detritus,  and  hyaline,  epithelial, 
fatty,  and  blood  casts. 

When  there  is  much  blood  present  it  will  settle  as  a  deep  red  collection 
at  the  bottom  of  the  urine  glass.  The  amount  of  albumin  is  corre- 
spondingly increased  with  an  augmentation  in  the  quantity  of  blood. 


416  SCARLET  FEVER 

Exceptionally  albumin  may  be  absent  for  a  number  of  days,  although 
casts  are  present;  on  the  other  hand,  a  considerable  quantity  of  albumin 
may  be  present  without  urinary  casts  being  found. 

The  specific  gravity  varies  greatly  according  to  the  amount  of  urine 
passed.  It  may  be  as  low  as  1004,  or  as  high  as  1040  or  more;  ordinarily 
it  will  be  between  1020  and  1035.  The  amount  of  urine  secreted  pro- 
gressively diminishes  in  severe  cases,  and  there  may  be  complete  sup- 
pression for  a  period  of  twenty-four  hours  or  longer.  Cases  in  which 
this  occurs  usually  succumb. 

The  reaction  of  the  urine  is  almost  invariably  acid.  The  quantity 
of  urea  excreted  varies  with  the  amount  of  urine,  but  is  usually  under 
2  per  cent. 

When  dropsy  occurs  the  urine  is  extremely  scanty,  high  colored,  of 
high  specific  gravity,  and  contains  an  abundance  of  albumin  and  casts. 

It  is  not  at  all  uncommon  for  the  albumin  to  disappear  every  now 
and  then  from  the  urine,  only  to  reappear  in  a  few  days.  We  have 
frequently  noted  this  irregularity  in  scarlatinal  albuminuria.  In  certain 
cases  the  albumin  appears  intermittently  in  the  urine.  At  other  times 
it  is  absent  at  certain  periods  of  the  day;  this  peculiarity  has  been 
observed  in  a  considerable  number  of  patients  in  certain  epidemics. 
This  occurs  independently  of  those  cases  in  which  albumin  is  absent 
while  the  patient  remains  in  a  recumbent  position,  but  reappears  when  a 
sitting  or  standing  position  is  assumed. 

These  observations  make  it  a  matter  of  importance  to  carefully 
examine  the  urine  at  frequent  intervals.  If  an  examination  is  made 
only  from  time  to  time,  albumin  which  is  intermittently  absent  or  which 
disappears  at  a  certain  time  of  the  day  may  be  completely  overlooked. 
It  is  a  good  plan  to  examine  the  urine  every  other  day  up  to  the  fifteenth 
day  of  the  disease  and  then  to  make  daily  analyses.  The  urine  should 
be  examined  both  for  albumin  and  microscopically,  and  the  amount 
passed  and  the  specific  gravity  should  be  ascertained.  With  the  use 
of  very  delicate  tests  small  quantities  of  albumin  will  doiibtless  be 
found  which  are  not  recognizable  by  the  usual  tests  employed.  For 
practical  purposes,  however,  the  nitric  acid  or  heat  test  will  suffice. 

In  cases  that  tend  toward  recovery  the  urine  increases  in  quantity, 
the  blood  and  casts  disappear,  and  the  albumin  gradually  diminishes. 

In  our  experience  the  urine  in  scarlet  fever  has  given  a  positive 
diazo  reaction  in  about  25  per  cent,  of  the  cases  examined.  This  reaction 
has  little  or  no  diagnostic  value. 

Aubertain^  and  Roger  have  each  reported  cases  of  scarlatinal  albumin- 
uria in  which  albumin  was  absent  in  the  mornings  while  the  patient 
remained  in  bed,  but  would  appear  soon  after  the  patient  stood  upon 
his  feet.  Ten  minutes'  standing  posture  in  one  case  would  produce  an 
albuminuria  lasting  about  two  hours.  Exercise  in  the  horizontal  position 
failed  to  excite  the  presence  of  albumin.  In  some  of  these  cases  of 
orthostatic  albuminuria  a  gradual  cure  takes  place;  others  eventuate 
in  a  permanent  albuminuria. 

1  L'Albuminurie  orthostatique  au  cours  de  la  nephrite  scarlatinense.    La  presse  m6d.,  1901. 


TIIK  COMPfJCA  T/ONS  OF  SCA  HI.KT  Fh'VPJfi  41  7 

In  some  cases  of  severe  nephritis,  particularly  when  the  urine  becomes 
greatly  reduced  in  cjuantity,  symptoms  of  uramia  are  prone  to  develof). 
These  usually  come  on  gradually  after  distinct  evidences  of  kidney 
involvement,  although  tliis  is  not  invariably  the  case.  Indeerl,  uncmia 
may,  in  rare  cases,  supervene  without  the  previous  existence  of  albumin- 
uria. Henoch  reports  such  a  case;  on  the  twelfth  day  of  scarlatina,  in 
a  four-year-old  child,  intense  right-sided  convulsions  and  stupor  devel- 
oped; examination  of  the  urine  on  the  previous  day  had  failed  to  show 
albumin.  The  patient  was  catheterized  on  the  development  of  the 
symptoms,  and  a  considerable  quantity  of  albumin  was  then  found. 

Ordinarily  the  first  symptoms  in  a  patient  about  to  develop  uraemia 
are  vomiting  and,  at  times,  diarrhoea.  This  is  doubtless  an  effort  on 
the  part  of  nature  to  eliminate  some  of  the  retained  poisons  through 
these  channels.  Leichtenstern  claims  that  one  of  the  most  frequent 
modes  of  onset  of  scarlatinal  uraemia  is  the  development  of  pronounced 
dyspnoea  associated  with  rapid  heart  action.  There  is  usually  some 
elevation  of  temperature,  which,  in  bad  cases,  may  become  excessive 
and  reach  106°  or  107°  F.  But  the  symptoms  referable  to  the  nervous 
system  dominate  the  clinical  picture.  There  are  frecjuently  intense 
headache,  tinnitus  aurium,  and  somnolence  or  stupor,  with  occasionally 
sudden  loss  of  vision.  These  symptoms  are  rapidly  followed  by  con- 
vulsions. The  convulsive  movements  may  be  partial,  that  is,  limited 
to  one  set  of  muscles,  as  those  about  the  jaws,  in  which  event  there 
may  be  a  tonic  contraction;  in  other  instances  they  are  unilateral  or 
general,  affecting  the  entire  body.  When  the  convulsions  are  limited 
to  certain  sets  of  muscles  consciousness  is  usually  preserved,  but  when 
there  is  a  general  epileptiform  seizure  it  is  followed  by  coma,  at  least 
for  a  time.  The  convulsive  attacks  may  be  of  brief  duration,  lasting 
but  a  few  minutes,  or  they  may  persist  for  an  hour  or  more.  There  may 
be  a  single  seizure,  although  more  commonly  there  is  a  succession  of 
convulsions  upon  the  same  or  successive  days. 

When  the  convulsions  are  severe  and  protracted,  death  may  result 
from  exhaustion,  cerebral  hemorrhage,  or  oedema  of  the  lungs.  In 
other  cases  a  fatal  termination  comes  on  later,  the  patient  lapsing  into 
a  progressively  deepening  coma.  In  some  cases  a  gradual  oncoming 
stupor  may  be  the  only  pronounced  symptom  of  urremia. 

In  favorable  cases  the  convulsions  cease,  the  stupor  disappears,  the 
urine  increases  in  quantity,  and  the  patient  emerges  from  the  crisis. 

The  amaurosis  which  develops  from  time  to  time  in  uraemia  usually 
disappears  when  the  convulsions  cease,  but  the  blindness  may  continue 
for  several  weeks,  ultimately  ending  in  complete  recovery.  In  some 
cases  aphasia  and  hemiplegia  may  develop  during  uraemic  conMalsions 
and  disappear  when  convalescence  is  established. 

In  rare  instances  patients  may  become  maniacal  after  ursemic  attacks. 
Wagner^  saw  a  patient  who  had  eleven  convulsive  seizures,  each  one 
being  followed  by  the  wildest  mania;  although  the  temperature  registered 
107.6°  F.,  the  patient  recovered. 

1  Quoted  bv  von  Jiirgensen,  loc.  cit. 
27 


418  SCARLET  FEVER 

Melancholia  may  also  develop  as  a  sequel  of  uraemia. 

If  the  urine  now  increases  in  quantity,  there  is  but  little  likelihood 
of  a  recurrence  of  the  severe  nervous  manifestations.  The  abnormal 
urinary  constituents  gradually  disappear  from  the  urine  and  the  patient 
is  entirely  restored  to  health. 

Prognosis. — The  prognosis  of  scarlatinal  nephritis  is  much  more 
favorable,  both  as  to  life  and  to  functional  restoration  of  the  kidneys, 
than  would  be  expected  from  the  nature  of  the  symptoms.  The  vast 
majority  of  patients  recover  from  the  nephritic  attack,  even  where 
alarming  urtemic  phenomena  have  been  present.  Intense  and  un- 
remitting headache,  protracted  convulsions,  repeated  vomiting,  and 
coma  are  symptoms  of  bad  omen.  The  quantity  of  albumin  in  the 
urine  is  no  reliable  guide,  as  a  severe  nephritis  may  exist  with  but 
little  albumin  in  the  urine,  and  the  converse  may  also  be  true.  The 
number  and  character  of  the  casts  and  particularly  the  quantity  of  the 
urine  are  more  important  criteria.  Suppression  of  urine  renders  the 
situation  extremely  grave,  although  recovery  may  take  place  if  diuresis 
can  again  be  established. 

The  opinion  has  prevailed  for  a  long  time  that  scarlatinal  nephritis 
was  but  seldom  followed  by  chronic  Bright's  disease.  While  it  is 
fortunately  true  that  restitutio  ad  integrum  usually  takes  place,  it  is 
nevertheless  certain  that  the  number  of  cases  of  permanent  nephritis 
following  scarlatina  has  been  much  underestimated. 

We  had  at  the  Municipal  Hospital,  during  the  winter  of  1902,  a  girl, 
aged  eight  years,  who  was  brought  in  with  a  well-marked  case  of  scar- 
latina from  a  hospital  where  she  was  being  treated  for  a  nephritis  said 
to  date  from  an  attack  of  scarlet  fever  five  years  previously.  She  had 
bloody  urine  for  some  days,  but  made  a  good  recovery  from  the  scarlatina 
and  left  the  hospital  many  weeks  later  still  suffering  from  a  chronic 
nephritis. 

Aufrecht^  reports  a  case  of  nephritis  after  scarlet  fever  lasting  twenty 
years,  and  terminating  in  a  contracted  kidney.  Leyden,  Litten,  Forch- 
heimer,  and  others  have  reported  cases  eventuating  in  chronic  Bright's 
disease.  Holt  says  that  he  formerly  believed  such  results  rare,  but 
larger  experience  has  convinced  him  that  this  sequel  is  not  uncommon. 
Of  77  cases  of  scarlatinal  nephritis  occurring  in  the  Southwestern 
Hospital  of  London,  in  1892,  6  cases,  according  to  Caiger,  were  dis- 
charged with  chronic  albuminuria  after  a  prolonged  residence. 

If  delicate  tests  for  albumin  were  employed  and  careful  microscopic 
examination  of  the  urinary  sediment  were  uniformly  made  for  months 
after  attacks  of  scarlatina,  it  would  doubtless  be  found  that  a  larger 
proportion  of  cases  eventuate  in  chronic  nephritis  than  has  been 
supposed. 

Many  of  these  patients  have  structurally  damaged  kidneys,  which  at 
some  future  period,  as  a  result  of  a  variety  of  causes,  may  be  reawakened 
into  activity.  The  practical  lesson  to  be  borne  in  mind  is  that  the 
urine  of  patients  convalescent  from  scarlatinal  nephritis  should  be 

1  Deutsche  ArchiT  f.  klin.  Med.,  Leipzig,  1887,  Bd.  xlii.  p.  517. 


77//';  aOMr/JCAT/ONS  OF  SdAlilJ'lT  FKVMIl  419 

carefully  exarniiHul  froin  lime  to  time,  and  tlie  did.  and  uuAc  fjf  life 
rcn;ulat('(l  accord inoly. 

Scarlatinal  Rheumatism  (Synovitis  Scarlatinosa^. — In  tlic  absence 
of  conclusive  evidence  that  acute  articular  rheumatism  is  a  specific 
tnorhid  process  due  always  to  the  same  infectious  a{2;ency,  we  are  justified 
iu  adlieriuf^  to  the  old  term  "scarlatinal  rlieumatism."  'J'he  attemy)t  tf) 
distiiifijuish  lu'tween  a  scarlatinal  synovitis  and  a  coini)licatin[(  rh(;niiia- 
tism  is  scarcely  warranted  by  our  present  knowledge  of  the  subject. 
Synovitis  and  arthritis  occurring  in  the  course  of  scarlet  fever  are 
frequently  associated  with  other  phenomena,  such  as  endocarditis, 
pericarditis,  pleurisy,  etc.,  which  are  common  rheumatic  coniphca- 
tions. 

The  frequency  of  joint  involvement  in  scarlatina  appears  to  vary  in 
different  countries  and  in  different  epidemics.  Trousseau  says:  "By 
minute  interrogation,  and  by  carefully  examining  and  applying  a  certain 
degree  of  pressure  to  the  joints,  articular  pains  are  found  to  be  present 
in  about  one-third  of  the  cases  (of  scarlatina).  It  is  important  to  know 
this;  for  acute  affections  of  the  joints,  general  arthritis,  pericarditis,  and 
endocarditis  frequently  occur  during  the  course  of  the  disease." 

Ashby  observed  synovitis  to  occur  20  times  among  900  cases  of 
scarlet  fever.  Koren,^  of  Christiana,  noted  scarlatinal  synovitis  of  a 
mild  type  27  times  in  426  cases  (6.3  per  cent.)  of  scarlet  fever  in 
the  epidemic  of  1875-77. 

Vogl  appears  to  have  observed  an  unusually  large  number  of  cases 
of  joint  complications  in  scarlatina.  He  is  authority  for  the  statement 
that  articular  involvement  occurred  in  13.6  per  cent,  of  the  cases  in  the 
epidemic  of  1884-85,  and  in  10.6  per  cent,  in  1894-95. 

Hodger^  saw  217  instances  of  scarlatinal  synovitis  among  3000  cases 
of  scarlet  fever,  or  3.2  per  cent. 

It  is  seen  from  the  above  figures  that  the  frequency  of  this  com- 
pHcation  varies  from  about  3  to  13  in  100  cases.  Our  personal 
experience  would  lead  us  to  regard  the  first  figure  (3  per  cent.)  as 
representing  more  nearly  the  average  incidence  of  this  complica- 
tion. 

Two  forms  of  joint  involvement  are  recognized — a  simple  serous 
synovitis  and  a  purulent  or  suppurative  arthritis.  The  mild  form  is 
fortunately  far  more  common  than  the  suppurative  variety.  Articular 
involvement  may  occur  at  any  period  of  the  disease,  but  is  most  common 
during  the  stage  of  desquamation  in  the  second  or  third  week  of  the 
disease.  The  wrists  and  fingers  are  the  joints  most  often  attacked, 
although  the  ankles  and  toes  not  infrequently  participate  in  the  process. 
Sometimes  the  larger  joints,  such  as  the  shoulders  and  knees,  become 
involved.  The  usual  symptoms  are  pain,  stift'ness,  and  swelling. 
Redness  may  or  may  not  be  present.  Trousseau  states  that  scarlatinal 
rheumatism  is  usually  mild  and  of  short  duration,  is  commonly  localized, 
and  when  it  disappears  does  not  tend  to  return.     We  have  seen  cases 

1  See  Johannsen,  loc.  cit.,  p.  195. 

-  See  Eichhorst's  Spec.  Pathol,  und  Therapie,  Leipzig,  1897,  p.  241 . 


420  SCARLET  FEVER 

in  which  there  were  periods  of  disappearance  and  of  recurrent  involve- 
ment. Scarlatinal  rheumatism  is  frequently,  although  not  always, 
attended  with  a  rise  of  temperature  which  commonly  reaches  101° 
or  102°  F. 

In  mild  cases  the  articular  inflammation  subsides  in  the  course  of 
three  to  five  days.    In  more  severe  cases  it  may  last  for  weeks. 

Suppurative  Arthritis. — Suppurative  arthritis  is  a  rare  complication  of 
scarlet  fever,  and  usually  occurs  late  in  the  course  of  the  disease.  The 
joint  becomes  painful,  swollen,  hot,  and  reddened;  the  fever  is  high,  the 
patient  prostrated,  and  all  of  the  usual  symptoms  of  pyaemia  are  present. 
One  or  several  articulations  may  be  involved.  In  the  vast  majority  of 
cases  a  fatal  termination  supervenes.  In  rare  instances,  through  surgical 
intervention,  or  even  at  times  without,  recovery  takes  place  after  a  long 
and  tedious  illness,  but  with  serious  impairment  of  the  functional 
activity  of  the  joints  involved. 

We  have  seen  scarlatinal  rheumatism  associated  in  one  case  with  a 
severe  endocarditis  and  a  recurring  geographic  erythema  of  the  trunk 
and  extremities,  and  in  another  fatal  case  with  endocarditis,  pleurisy, 
and  hemorrhagic  purpura. 

In  persons  of  scrofulous  habit  a  scarlatinal  synovitis  may,  after  a 
long  course,  eventuate  in  tuberculosis  of  the  joint  (white  swelling). 

In  rare  cases  of  scarlet  fever  the  sheaths  of  tendons  may  undergo 
inflammation  (tenosynovitis),  which  commonly  terminates  in  suppu- 
ration. In  other  cases  periarticular  abscesses  may  occur  and  rupture 
into  one  of  the  large  joints. 

Cases  of  periostitis  and  ostitis  have  been  reported,  involving  particu- 
larly the  petrous  portion  of  the  temporal  bone,  the  nasal  bones,  and  the 
cervical  vertebrae. 

Briick^  describes  a  form  of  scarlatinal  myositis,  which  attacks  most 
commonly  the  lumbar,  pectoral,  abdominal,  and  intercostal  muscles, 
and  which  is  characterized  by  pain  and  soreness  and  moderate  rise  of 
temperature. 

Purpura  Hemorrhagica. — It  is  important  to  distinguish  between 
true  hemorrhagic  scarlatina  and  secondary  purpura  developing  during 
the  course  of  the  disease.  The  former  condition  appears,  as  a  rule,  at 
the  outset,  and  is  characterized  by  constitutional  symptoms  of  great 
intensity  and  malignancy,  associated  with  hemorrhages  into  the  skin 
and  from  the  mucous  membranes. 

Purpura  hemorrhagica  comes  on  usually  after  the  subsidence  of  the 
acute  scarlatinal  symptoms  and  not  infrequently  during  convalescence. 
Most  cases  develop  during  the  second  or  third  week,  and  most  commonly 
from  the  fourteenth  to  the  twentieth  day.  The  patient  loses  appetite, 
is  apathetic,  and  may  have  some  rise  of  temperature.  Nose-bleed  is 
often  one  of  the  first  symptoms;  soon  pinhead-sized  purpuric  spots 
appear  upon  the  skin  of  the  trunk,  extremities,  or  face;  the  gums  become 
swollen  and  bleed;  the  urine  contains  blood,  and  hemorrhage  may  take 

1  Petersb.  med.  Presse,  1896,  No.  18. 


77//';  aOMPfJCATfO.VS  OF  SCAIILFT  FHVI'Ht 


421 


place  from  \\\v.  stomach  and  l)()wcls.  A  inarkcd  pallor  srjon  fjevelops, 
the  patient  l)(!Conies  ])ro.strate(l,  and,  in  seven;  eases,  d(;atii  takes  place 
from  loss  (^f  hlood,  Jieniorrhafre  into  the  brain,  or  (;xhaustion. 

AlhiHTiiiniria  is  usually  j)resent,  even  when  the  urine  is  free  of  Vjlood. 

In  mild  cases  the  hemorrhages  from  the  various  mucous  membranes 
cease  after  a  short  time,  and  the  patient,  although  intensely  ansemic, 
recovers. 

These  secondiiry  purpuras  are  not  seen  alone  in  scarlatina,  but  in 
other  infectious  diseases,  such  as  influenza,  rheumatism,  smallpox,  etc. 
They  are  probably  due  to  some  secondary  infection  which  rlestroys 
either  the  integrity  of  the  blood  or  the  vessel  walls.  We  have  seen  two 
cases  of  heinorrliagic  purpura  comj)licating  scarlatina. 

A  three-year-old  child,  suifering  from  a  well-marked  scarlatina, 
developed  late  in  the  course  of  the  disease  swelling  of  the  joints,  diffuse 


Fir,.  74 


Purpura  hemorrhagica  associated  with  pleurisy,  endocarditis  and  joint  trouble,  complicating 
scarlet  fever.    Fatal  termination. 


ecchymotic  patches  upon  the  face,  trunk,  and  extremities,  and  endo- 
carditis. The  patient  after  some  days'  illness  died.  Autopsy  showed 
vegetations  upon  the  mitral  and  aortic  valves,  a  right-sided  pleurisy, 
and  hemorrhages  into  the  mediastinal  and  peritoneal  cavities. 

The  second  case  was  a  girl,  aged  eight  years,  who,  upon  the  seven- 
teenth day  of  a  scarlatina  of  average  severity,  became  apathetic,  had 
slight  rise  of  temperature,  and  nose-bleed.  The  following  day,  small, 
pinpoint  petechia  appeared  upon  different  parts  of  the  body,  bleeding 
occurred  from  the  gums,  and  an  abundance  of  blood  was  found  in  the 


422  SCARLET  FEVER 

urine.  The  bleeding  continued  for  a  few  days,  but  ceased  under  treat- 
ment and  the  patient  made  a  good  recovery.  A  pronounced  ansemia 
persisted  for  a  few  weeks.  Albuminuria  was  present  even  after  the 
cessation  of  hsematuria. 

Although  this  complication  is  uncommon,  a  number  of  cases  have 
been  published.  Biss^  reports  the  case  of  a  boy,  aged  three  and  one- 
half  years,  who  suffered  from  a  severe  attack  of  scarlet  fever  compli- 
cated by  double  otitis  media.  On  the  nineteenth  day  after  admission 
to  the  hospital  he  developed  an  extensive  eruption  of  pinpoint  hemor- 
rhages over  the  trunk  and  limbs,  vomited  a  half-pint  of  blood,  passed  a 
similar  quantity  by  the  bowel,  and  rapidly  succumbed.  Autopsy  showed 
the  kidneys  to  be  "  transformed  almost  entirely  into  fat." 

Murray^  saw  a  two-year-old  colored  child  develop  scarlatina  after  an 
operation  for  hernia.  On  the  ninth  day  of  the  attack  there  occurred 
bleeding  from  the  kidneys,  bowels,  stomach,  nose,  and  gums,  and 
hemorrhages  into  the  skin  and  conjunctivae.  The  red  corpuscles 
numbered  2,000,000  per  cubic  centimetre.  Urine  contained  blood  and 
epithelial  and  hyaline  casts.     Death  took  place  on  the  fourteenth  day. 

De  Boinville^  places  on  record  the  case  of  a  boy,  aged  four  and  one- 
half  years,  who,  on  the  sixteenth  day  of  scarlet  fever,  had  hemorrhages 
from  the  nose  and  hemorrhagic  spots  on  the  scalp  and  about  the  knees. 
Although  the  amount  of  blood  lost  was  small,  the  epistaxis  could  not 
be  checked  and  the  patient  died  five  days  later. 

Phillips*  reports  the  case  of  a  girl,  aged  fourteen  years,  suffering  from 
scarlet  fever,  who  had  a  recurrent  rash  on  the  fourteenth  day,  and 
swelling  of  the  joints  on  the  twentieth  day;  six  days  later  petechial 
patches  on  the  chest  and  legs  and  free  bleeding  from  the  nose,  gums, 
and  kidneys.  Patient  had  albuminuria  and  acute  dilatation  of  heart, 
but  recovered. 

Gangrene. — Mention  has  already  been  made  of  the  sloughing  of 
the  tissues  of  the  neck,  which  occasionally  accompanies  cellulitis  and 
abscesses.  The  muscles  and  large  bloodvessels  of  the  neck  may  be 
exposed  by  gangrene  of  the  overlying  skin. 

Gangrenous  stomatitis,  or  noma,  is  also  seen  at  times  after  scarlatina, 
although  it  is  much  rarer  than  after  measles.  Apart  from  these  con- 
ditions, a  form  of  spontaneous  gangrene  is,  in  rare  instances,  observed 
during  the  course  of  scarlatina.  When  seen,  gangrene  usually  develops 
during  the  second  or  third  week  of  the  disease,  and  usually  attacks  the 
extremities.  In  most  of  the  reported  cases  the  condition  has  been 
attributed  to  embolism.  There  appear  first  bluish  discoloration,  pain, 
and  coldness,  and  then  hemorrhagic  extravasation  into  the  skin.  In 
some  of  the  reported  cases  the  gangrene  was  so  deep  and  extensive  as 
to  necessitate  amputation  of  the  affected  member. 

1  Lancet,  August  2,  1902,  p.  286. 

-  Case  of  Scarlet  Fever  with  Purpura,  Lancet,  February  11,  1893,  vol.  1. 

3  A  Peculiar  Case  of  Scarlatina  Hemorrhagica,  Lancet,  August  9,  1903.  This  case  is  evidently  a 
purpura  hemorrhagica,  and  not  one  of  true  hemorrhagic  scarlatina. 

*  Scarlet  Fever  with  Relapse  ;  Acute  Rheumatism  and  Purpura  Hemorrhagica ;  Recovery.  London 
Lancet,  1893,  vol.  ii. 


TIII<:  COMPLKIATinXS  OP'  SCARL/'JT  FKVI'Hi  423 

.  Cases  of  gangrene  have  been  reported  by  Blanpain/  Hudson,*  Kiister,' 
and  Chapin/ 

Wood  and  Arrigoni'"'  ?iave  reported  oases  of  gangrene  affecting  the 
genitaha,  and  Wilson"  a  case  of  gangrene  of  the  face  occurring  three 
weeks  after  convalescence  from  scarlatina. 

Pearson  and  Littlewood^  rey)ort  the  case  of  a  boy,  aged  ff)ur  years, 
who,  after  an  ordinary  scarlet  fever,  on  the  eighth  day  developed  small, 
hemorrhagic  discolorations  of  the  skin  of  both  legs.  In  a  few  days 
the  legs  became  livid,  first  upon  the  feet,  thence  spreading  upward. 
The  femoral  pidsation  was  lost,  the  legs  became  cold,  intermittent 
pain  occurred,  and  lines  of  demarcation  formed  about  three  inches 
above  the  knees.  At  the  same  time  slight  dilatation  of  the  heart  was 
discovered.  On  the  twenty-third  day  of  the  disease  the  right  leg  was 
amputated,  and,  a  week  after,  the  left.  The  patient  recovered.  Embolic 
and  thrombotic  clots  were  found  in  the  bloodvessels  of  the  amputated 
limbs. 

Buchan*  reports  the  case  of  a  boy,  aged  thirteen  years,  whose 
scarlatinal  rash  on  the  second  day  exhibited  a  bluish  appearance  on 
the  legs.  A  few  days  later  the  veins,  especially  at  the  apex  of  Scarpa's 
triangle,  stood  out  quite  prominently.  Hemorrhages  occurred  into  the 
skin  of  the  legs,  particularly  the  right;  there  were  also  hsematuria, 
nose-bleed,  and  ha?moptysis.  The  lower  part  of  the  right  leg  became 
mummified  and  a  definite  line  of  demarcation  formed  just  above  the 
knee,  where  an  amputation  was  performed.  The  patient  made  a  rapid 
recovery. 

We  recall  a  child  treated  in  the  Municipal  Hospital  in  1900,  who 
developed  gangrene  about  the  third  week  of  a  severe  scarlatina.  Ecchy- 
motic  patches  developed  upon  the  leg,  followed  by  rather  superficial 
sphacelation  of  the  tissues.  A  few  days  later  one  hand  became  blue 
and  cold,  and  shortly  after  this  the  other  hand  became  similarly  affected. 
The  radial  pulse  was  lost  and  both  hands  assumed  an  indigo-blue 
color.  Before  actual  gangrene  could  take  place  the  child,  who  was 
greatly  prostrated,  died.  The  gangrene  in  this  case  was  doubtless  due 
to  embolism  (Fig.  75 j. 

Skin  Complications. — Reference  has  already  been  made  to  the 
various  abnormalities  of  the  rash  of  scarlet  fever,  including  an  excessive 
development  of  miliary  vesicles.  It  remains  to  discuss  the  occasional 
complicating  skin  disorders  which  are  quite  apart  from'  the  scarlatinal 
process. 

1  Scarlatine ;  gangrene  spontaneti  des  membres  ;  embolies  ;  autopsie.  Aroh.  Med.  Beiges,  Brux., 
1869,  2,  ix.  pp.  324-334. 

-  Scarlatina  Resulting  in  Mortification  of  the  Right  Limb,  and  Sacceesful  Amputation.  Transac- 
tions of  the  Ohio  Medical  Society,  1858. 

^  Spontan.  Gangran  des  Unter-schenkels  nach  scarlatina:  Ampntatio  Femoris :  Tod.,  KasECl, 
1876  and  1878. 

*  An  Unusual  Result  of  Scarlet  Fever;  Embolus;  Gangrene  :  Amputation.  Medical  Age,  Detroit, 
1884,  xi.  p.  205. 

*  Quoted  by  Thomas.  ^  Reviewed  in  Archiv  f.  Kinderheilk.,  1?98,  p.  418. 

7  Dry  Gangrene  of  Both  Legs  ;  Double  Amputation,  1897, 11,  p.  84. 

8  Lancet,  October  5, 1901,  p.  915. 


424  SCARLET  FEVER 

Febrile  herpes  occurs  every  now  and  then  during  the  invasive  stage 
of  the  disease.  The  patches  develop  usually  about  the  mouth,  although 
they  may  be  situated  about  the  cheeks  or  ears.  While  herpes  is  not 
very  frequent  in  scarlet  fever  it  is  more  commonly  seen  than  in  smallpox 
or  measles. 

Urticaria  is  not  an  infrequent  accompaniment  of  scarlet  fever,  although 
it  cannot  be  considered  as  bearing  any  special  relation  to  the  disease. 
It  may  be  seen  early  or  late  in  the  course  of  the  illness,  and  is  usually 
neither  extensive  nor  protracted.  This  complication  is  doubtless  due 
to  the  presence  in  the  blood  of  some  accidental  toxin  or  drug. 

Blehs  may  occasionally  develop  upon  the  skin  as  a  result  of  a  coa- 
lescence of  neighboring  miliary  vesicles  in  intense  rashes.  Thomas  says 
that  they  may  reach  the  size  of  hazel-nuts.  Bullae  may  also  occur  upon 
patches  which  are  destined  to  terminate  in  gangrene  of  the  skin.    Some 

Pig.  75 


Gangrene  of  the  skin  complicating  scarlet  fever.    Patient  developed  gangrene  of 
both  hands  and  died. 

authors  speak  of  the  occurrence  of  pemphigus,  particularly  in  certain 
epidemics.  These  are,  in  all  probability,  not  true  instances  of  pemphigus, 
but  of  bullous  dermatitis  of  septic  origin. 

We  have  occasionally  seen  cases  of  localized  necrosis  of  the  skin  in 
small  areas,  a  condition  analogous  to  the  so-called  varicella  gangrsenosa, 
but  better  designated  dermatitis  gangranosa.  Fig  76  shows  this  condi- 
tion upon  the  knees  of  a  young  boy. 

Eczema  may  occur  as  a  complication  of  scarlatina,  but  is  more  apt 
to  develop  as  a  sequel.  Intense  desquamation  may  leave  the  skin  dry, 
harsh,  and  fissured,  and  the  seat  of  eczematoid  patches;  these  may 
persist  for  some  time  after  convalescence.  In  other  cases  a  purulent 
discharge  from  the  ears  or  nose  may  give  rise  to  an  impetiginous  eczema 
in  the  region  of  these  orifices ;  the  skin  becomes  moist  and  covered  with 
crusts  as  the  result  of  the  irritating  and  infective  discharges. 


77//';  aOMI'LICATIONS  OF  SCA.'i'fJ'JT  FFVI-'Ji  425 

Cutaneous  ahscas.sr.s-  may  occur  iijxjii  any  portion  of  ttx;  integument. 
This  compliciition  is  iincoinmoii,  usually  occurrinj^  in  scplic  cases.  We 
recall  an  adult  })alicnt  in  whom  a,  lar<i;c  nunihcr  of  srn;ill  abscesses 
occurred  in  the  skin. 

Furuncles  may  develop  during  an  attack  of  scarlet  fever,  altouhgh 
they  are  more  apt  to  a|)pear  after  the  termination  of  the  disease.  In  a 
severe  case  seen  recently  they  complicated  an  unrecogni/erl  anrl  un- 
treated nephritis,  after  convalescence  from  scarlatina  had  taken  place. 

Phlebitis. — Phlebitis  appears  to  be  a  rare  complication  of  scarlet  fever. 
The  veins  of  the  neck,  upper  extremities,  and  cranial  cavity  are  those 
most  apt  to  ])e  affected.  The  cases  in  which  this  complication  develop.s 
are  usually  severe;  the  ])hlebitis  not  uncommonly  occurs  in  the  neighbor- 
hood of  suppurating  glands  or  abscesses. 

Fio.  76 


Dermatitis  gaugrjenosa  occurring  in  a  severe  case  of  scarlet  fever.    (This  condition  is  analogous 
to  the  so-called  "varicella  gangrsenosa.") 

Cases  have  been  reported  by  Rees,^  Hofnagels,-  von  Jiirgensen,^  and 
Moizard  and  Ulmann.*  The  latter  writers  were  able  to  collect  from 
the  literature  but  four  cases  of  phlebitis  after  scarlatina.  In  their  own 
case,  a  phlebitis  of  the  right  axillary  and  humeral  veins,  cultures  demon- 
strated the  condition  to  be  due  to  a  streptococcic  septicaemia. 

Roger^  has  recently  published  an  account  of  a  woman,  aged  forty- 
nine  years,  who  died  on  the  eleventh  day  of  a  severe  scarlatina,  after 
suffering  for  three  days  with  a  phlebitis  of  the  crural  vein.  Autopsy 
showed  vegetations  on  the  auricular  surface  of  the  mitral  valve. 

Alimentary  Canal.— Reference  has  already  been  made  to  the  con- 
dition of  the  mouth  and  throat  in  scarlatina. 

1  Fatal  Phlebitis  After  Scarlet  Fever,  London  Lancet,  1S62,  ii.  p.  63. 

-  Ann.  Soc.  de  mod.  d'Anvers,  184S,  ix.  pp.  333-345.  "  Loc.  cii. 

*  La  phlebite  scarlatineuse,  Archiv  de  med.  des  enfauts,  1S99,  vol.  ii  ,  Ko.  10.  p.  601. 

'  Log.  cit.,  p.  962. 


426  SCARLET  FEVER 

The  vomiting,  which  is  so  common  at  the  beginning  of  scarlet  fever, 
is  seldom  sufficiently  intense  or  protracted  to  unfavorably  influence  the 
course  of  the  disease.  In  hemorrhagic  scarlet  fever  the  material  vomited 
may  contain  blood.  At  a  later  stage  of  the  disease  vomiting  may  be  an 
expression  of  nephritis,  or,  when  repeated,  of  an  oncoming  uraemia. 
Thomas  says  that  severe  gastralgia,  persistent  and  often  bilious  vomiting, 
and  great  sensitiveness  of  the  stomach  to  all  food,  occur  in  some  cases; 
we  have  never  observed  such  severe  gastric  symptoms.  Pathological 
changes  have  frequently  been  described  as  occurring  in  the  walls  of 
the  stomach,  but  it  would  seem  that  in  many  cases  these  do  not  give 
rise  to  pronounced  symptoms. 

In  the  period  of  invasion  and  the  early  eruptive  stage  it  is  not  at  all 
rare  for  diarrhoea  to  manifest  itself.  In  ordinary  cases  this  is  due  to 
a  simple  catarrhal  enteritis  which  yields  of  its  own  accord  or  to  simple 
treatment.  In  very  severe  cases  of  scarlatina,  however,  the  bowel 
movements  may  be  frequent  and  profuse,  and  accompanied  by  pain  and 
tympanitic  distention.  If  the  diarrhoea  is  protracted  the  tongue  becomes 
dry,  the  eyes  sunken,  and  the  face  pinched.  This  complication  under 
such  circumstances  is  much  to  be  feared,  leading,  as  it  may,  to  exhaustion 
and  a  fatal  termination. 

JoeP  saw  a  patient  in  whom  severe  gastrointestinal  symptoms  and 
high  fever  were  the  most  conspicuous  symptoms;  slight  angina,  subse- 
quent scaling,  and  an  attack  of  scarlet  fever  in  the  sister  made  the 
diagnosis  clear. 

In  the  later  stages  of  the  disease  there  is  occasionally  encountered 
a  dysenteric  condition,  characterized  by  frequent,  small,  bloody,  or 
catarrhal  stools  and  painful  tenesmus. 

Litten^  speaks  of  diarrhoeas  of  typhoidal  character.  There  is  marked 
distention  of  the  abdomen,  and  critical  hemorrhages  from  the  bowel 
may  occur.  The  stools  are  liquid,  of  a  pale-yellow  color,  and  dotted 
with  whitish  specks.  This  condition  is  associated  with  a  protracted 
remittent  fever,  dry  tongue,  pronounced  apathy,  and  later  renal  com- 
plications. When  the  patient  recovers,  convalescence  is  long  drawn  out. 
On  autopsy  in  these  cases  there  is  enlargement  of  the  spleen  and  the 
mesenteric  glands,  swelling  of  Peyer's  patches  and  of  the  solitary 
follicles,  the  latter  at  times  exhibiting  erosion. 

Liver.^ — ^The  liver  is  generally  increased  in  size,  the  inferior  border 
often  extending  below  the  false  ribs.  Hepatic  enlargement  is,  however, 
not  constant,  and  the  liver  may,  in  severe  cases,  be  much  diminished 
in  size  as  a  result  of  degeneration  and  atrophy.  Jaundice  is  not  a 
common  symptom,  but  it  is  encountered,  according  to  some  authors, 
with  especial  frequency  in  certain  epidemics. 

Mild  jaundice  has  no  special  significance,  but  severe  cases  may 
indicate  extensive  fatty  degeneration  of  the  liver. 

Roger^  says  that  lesions  of  the  liver  often  explain  different  forms  of 
delirium  and  modifications  of  temperature.    He  mentions  the  case  of  a 

1  Quoted  by  Thomas.  2  CharitiS-Annalen,  Bd.  vii.  p.  128. 

3  Loc.  cit.,  p.  1055. 


Tllh:  aOMPfJCATff):\'S  OF  SCAJifJ-ri'  FICVFJi  427 

confirmed  nineteen-year-old  alcoholic  .sufFerin^  from  scrarlatina,  who 
had  severe  delirium  of  the  ty])c  of  delirium  tremens  early  in  the  disease. 
The  liver  was  lar^e  and  f)al])jihlc;  the  urine  was  free  of  albumin.  The 
patient  died  three  days  later,  with  a  iem[)erature  hiirely  above  normal. 
The  liver  nt  auto})sy  was  found  to  be  huge  and  comf>letely  d(;generated. 

Respiratory  Organs. — The  larynx  may  become  involved  as  a  result 
of  a  secondary  diphtheria  or  a  membranous  inflammation  of  strepto- 
coccic origin,  although  the  latter  is  much  rarer  than  in  measles.  CP^Jema 
of  the  glottis  results  at  times  from  extension  of  inflammation,  and  on 
other  occasions  from  nephritis. 

Perichondritis  of  the  larynx  is  a  rare  and  fatal  complication.  Accord- 
ing to  Kraus^  it  occurs  about  once  in  200  to  250  cases  of  scarlatina. 
Rauchfuss  saw  4  cases  among  903  cases  of  scarlatina,  and  Leichtenstern 
2  cases  among  467  patients.  Its  development  may  necessitate  the 
performance  of  intubation  or  tracheotomy. 

Pulmonary  complications  are  much  less  common  in  scarlatina  than  in 
measles.  The  bronchial  tubes  and  lungs,  are  nevertheless,  according  to 
Henoch,  much  more  frequently  involved  in  bad  cases  than  is  generally 
believed.  These  lesions  are  masked  by  the  severe  constitutional  symp- 
toms, and  are  often  not  discovered  until  autopsy.  In  a  series  of  98  fatal 
cases  of  scarlatina,  reported  by  McCollom,^  15  were  due  to  broncho- 
pneumonia. 

As  would  naturally  be  expected,  pulmonary  complications  are  com- 
moner in  infants  than  in  older  children  and  adults.  Roger^  gives  the 
following  morbidity  and  mortality  statistics  of  pulmonary  complications 
in  scarlatina  according  to  age: 

Scarlatina.  No.  of  patients.  Cases  of  pneumonia.  Mortality. 

First  infancy      ...        56  6  (10.7  per  ct.)  5  (8.9  per  ct). 

Childhood  ...      430  6   (1.3  per  ct.)  2  (0.4  per  ct.). 

Adults         ....    1727  4   (0.2  per  ct.)  3  (0.1  per  ct.). 

All  of  the  pneumonias  in  the  infants  were  bronchopneumonias. 
Four  of  the  children  of  the  second  group  had  bronchopneumon'a,  and 
two  had  apical  pneumonia.    Bronchopneumonia  occurred  in  two  adults. 

Bronchopneumonia  in  severe  cases  appears  usually  during  the  first 
or  second  week.  Henoch  remarks:  "We  found  bronchitis  and  broncho- 
pneumonia in  nearly  all  the  severe  cases  and  also  repeatedlv  during 
life." 

Lobar  Pneumonia. — Lobar  pneumonia  may  develop  dur  ng  the 
height  of  the  disease,  or  more  commonly  after  nephritis  has  manifested 
itself.  The  upper  lobes  are  more  often  affected  than  other  parts  of 
the  lungs. 

(Edema  of  the  Lungs. — CEdema  of  the  lungs  is  by  no  means  a  rare 
complication  when  the  kidneys  are  severely  affected  and  a  general 
dropsy  exists.  Serous  transudation  into  the  lungs  may  occur  rapidly 
and  lead  to  sudden  death. 

Involvement    of    the    pleural   cavities   in   scarlatina    is    uncommon. 

1  Prag.  med.  Wochenschr.,  1899,  pp.  29  and  30. 

-  Quoted  by  Corlett,  loc.  cit.  s  Loc.  cit,  p.  9?3. 


428  SCARLET  FEVER 

Pleurisy  may  develop  in  association  with  a  lobar  pneumonia  or  it  may 
occur  independently  thereof.  The  process  may  be  dry  or  accompanied 
by  serous  or  purulent  exudate;  scarlatinal  pleurisies  show  a  pronounced 
tendency  to  eventuate  in  empyema,  a  complication  which  adds  much 
gravity  to  the  disease.  However,  desperate  cases  may  at  times  terminate 
favorably,  as  is  evidenced  in  a  remarkable  case  of  Trousseau,  who 
drew  off  from  the  chest  of  a  fourteen-year  old  girl  750  grams  of  pus, 
the  patient  making  a  complete  recovery. 

Thomas  says  all  forms  of  scarlatinal  pleurisy  are  characterized  by 
rapid  development  and  by  but  slight  local  disturbance,  even  when 
the  affection  is  very  intense.  The  effusion  is  usually  present  only  upon 
one  side. 

Pleural  involvement  is  more  frequent  in  cases  complicated  by  nephritis. 
It  is  especially  apt  to  accompany  scarlatinal  rheumatism.  We  have 
already  referred  to  a  patient  treated  in  the  Municipal  Hospital,  who  had 
purpura,  endocarditis,  synovitis,  and  a  fibrinous  pleurisy. 

Farb ringer  regards  exudative  pleurisy  as  a  frequent  complication, 
occurring,  in  his  experience,  in  5  per  cent,  of  cases  of  scarlatina.  Johan- 
nesen,  of  Norway,  found,  among  688  deaths  from  scarlet  fever,  but 
3  that  resulted  from  pleurisy. 

Nervous  System. — While  the  onset  of  scarlatina  is  attended  in  severe 
cases  by  pronounced  nervous  symptoms,  these  subside  if  the  course  is 
favorable,  and  do  not  add  to  the  gravity  of  the  disease.  The  early 
cerebral  manifestations  are  in  part  due  to  the  scarlatinal  poison  and 
in  part  to  the  high  fever.  Headache  and  dehrium  may  be  present  in 
ordinary  cases,  but  convulsions  and  coma  presage  an  attack  of  great 
severity. 

Later  in  the  disease  severe  nervous  symptoms,  such  as  delirium, 
convulsions,  coma,  sudden  blindness,  etc.,  may  develop  as  a  result 
of  uraemia. 

Hemiplegia. — Hemiplegia  may  occur  early  from  a  cerebral  hemor- 
rhage during  the  invasive  convulsions,  or  it  may  come  on  at  a  later  date 
as  the  result  of  embolism.  Taylor^  reports  a  right  hemiplegia  resulting 
from  embolism  of  the  middle  cerebral  artery;  the  patient  succumbed 
later  to  diphtheria. 

Addy^  saw  a  case  of  partial  hemiplegia  with  amnesia  after  scarlatina. 

Meningitis. — Meningitis  usually  results  from  extension  of  inflam- 
mation and  infection  from  the  middle  ear  or  the  nasal  sinuses.  We 
have  already  referred  to  a  case  of  purulent  meningitis  of  the  base  of 
the  cerebellum  which  we  observed  after  a  purulent  otitis  media.  Roger^ 
saw  a  twenty-three-year-old  man  in  whom  a  severe  purulent  rhinitis 
complicating  scarlatina  was  followed  by  meningitis.  At  autopsy  the 
left  frontal  lobe  of  the  brain  was  covered  with  purulent  plaques  and 
the  left  sphenoidal  sinus  contained  pus.  The  presence  of  the  strepto- 
coccus in  pure  culture  was  demonstrated.     Similar  cases  have  been 

1  Medical  Times  and  Gazette,  London,  18S0,  ii.  p.  686. 

2  Glasgow  Medical  Journal,  1880-85,  S.  xiii.  pp.  463-465. 

3  Loc.cit.,  p.  850. 


77//';  COMI'fJdATIONH  OF  SCARI.F/I'  FFVKR  429 

reported  by  other  observers.  Jiaudelocque'  reports  a  case  of  meningo- 
encepliiilitis  characterized  by  headache,  vomiting,  and  convulsions, 
followed  by  coina  and  the  loss  of  speech,  hearing,  and  sight.  Althous^ 
reports  a  case  of  spinal  meningitis  with  consecutive  lateral  and  pos- 
terior sclerosis. 

Incomplete  Paraplegia. — Cases  of  incomplete  paraplegia  have  been 
described  by  Dcinange,''  Roger,  and  others.  Roger  says  that  among 
22b'3  patients  with  scarlatina  4  cases  of  incomplete  paraplegia  were 
observed.  Three  women  liad  for  al)Out  a  week  great  difficulty  in 
standing  up  or  walking.  The  fourth  patient  was  a  man  who  on  the 
second  day  of  the  disease  had  paralysis  of  the  soft  palate.  Later  the 
two  legs  and  the  right  arm  became  affected ;  the  palsy  passerl  off  in  ten 
days.  Cultures  from  the  throat  excluded  the  possibiHty  of  diphtherial 
infection. 

As  has  already  been  stated,  facial  palsy  occurs  occasionally  from 
involvement  of  the  facial  nerve  in  the  bony  roof  of  the  ihiddle  ear. 

Insanity. — Insanity  has  been  reported  as  a  complication  and  sequel 
of  scarlatina.  The  mental  aberration  is  usually  temporary,  but  may  in 
some  cases  persist  after  convalescence.  Mitchell,*  Rabuske,  and  Wagner 
have  each  reported  attacks  of  acute  mania  in  scarlet  fever,  the  mania 
in  the  last-named  case  following  ursemic  convuls  ons. 

Carrieu''  records  a  case  of  dementia  and  Brill  a  case  of  scarlatinal 
insanity  with  epilepsy.  Wildermuth,"  in  a  report  of  1S7  cases  of  epilepsy, 
states  that  12  cases  followed  attacks  of  scarlet  fever. 

Multiple  Neuritis. — Egis^  reports  a  case  of  multiple  neuritis  following 
scarlatina  in  which  there  was  an  ataxic  gait  and  paralysis  of  both 
peroneal  nerves.  But  two  other  cases  of  multiple  neuritis  could  be 
found  in  literature. 

Tetany. — Steffen^  reports  a  case  of  tetany  in  a  young  girl  suffering 
from  scarlatina;  an  attack  was  noticed  after  each  bath.  Kiihn-Ulsar^ 
mentions  a  case  of  tetany  in  a  boy,  aged  four  and  one-half  years,  suffering 
from  scarlet  fever.  For  six  weeks  muscular  spasms  and  stiffness  were 
noted,  at  times  limited  in  extent  and  at  other  times  general.  Trismus 
was  present  for  fourteen  days.    The  patient  gradually  recovered. 

Bones. — Necrosis  of  the  petrous  portion  of  the  temporal  bone  and  of 
the  ear  ossicles  occurs  in  severe  cases  of  purulent  otitis  media.  Necrosis 
of* other  bones  sometimes  takes  place.  Brown^°  reports  a  case  of  necrosis 
of  the  lower  maxilla  after  scarlet  fever,  and  Weickert^^  reports  a  case 
in  which  both  jaws  were  thus  affected. 

Neumark^^  reports  30  cases  of  acute  infectious  osteomyelitis,  of  which 
5  follow^ed  scarlet  fever. 

1  Gaz.  des.  hop.  de  Paris,  1887,  xi.  pp.  197-199.  =  Brit.  Med.  Journal,  1S81,  i.  p.  50. 

3  Bull.  Soc.  anat.  de  Paris,  1874,  pp.  503-9. 
<  Edinburgh  IMedical  Journal,  1881-82,  xxvii.  pp.  721-24. 

6  New  England  Medical  Monthly,  1882-83,  ii.  pp.  55-58.  «  Quoted  by  Holt,  loc.  cit. 

'  Archiv  f.  Kinderheilk.,  1900,  sxviii.  s  Jacobi's  Festschrift,  1900,  p.  83. 

9  Berliner  klin.  Wocheuschrift,  1899,  No.  39,  p.  855. 
10  London  Lancet,  1844,  i.  p.  220. 
1'  Deutsche  Klinik,  Berlin,  1854,  vi.j).  22.  i=  Archiv  f.  Kinderheilk..  Bd.  xxii. 


430  SCARLET  FEVER 

Sequelae. — But  few  words  will  be  devoted  to  the  sequelae  of  scarlatina, 
as  they  represent  merely  a  continuation  of  the  complications  or  dis- 
abilities resulting  from  structural  damage. 

A  weakened  and  anaemic  state  of  the  system  may  develop  after 
scarlatina  as  after  many  other  infectious  diseases;  the  patient  is  thus 
lowered  in  resisting  power  and  rendered  more  susceptible  to  the  other 
infectious  diseases.  There  is,  however,  no  such  increased  susceptibility 
to  tuberculosis  as  exists  in  patients  recovering  from  measles. 

The  various  organs  of  sense  may  bear  for  a  long  time  and  in  some 
cases  forever  the  marks  of  a  cruel  scarlatinal  attack.  The  mucous 
membrane  of  the  eyes,  throat,  and  nose  may  show  persistent  pathological 
alteration. 

It  is  the  ears,  however,  that  most  frequently  exhibit  permanent 
damage.  It  is  largely  because  of  injury  to  the  sense  of  hearing  that 
scarlatina  is  so  feared  by  the  laity.  A  chronic  purulent  otitis  media 
-may  persist  after  scarlatina  and  lead  at  a  remote  date  to  mastoid  or 
intracranial  disease.  Destructive  changes  involving  the  middle  ear 
and  the  contained  ossicles  may  cause  auditory  disability,  varying  in 
degree  from  slight  impairment  of  hearing  to  complete  deafness.  When 
this  occurs  very  early  in  life  the  loss  of  this  sense  may  lead  to  deaf- 
mutism. 

As  has  already  been  suggested,  the  damage  to  the  kidneys  is  often 
more  than  a  transitory  one.  In  a  certain  proportion  of  cases  albuminuria 
will  persist  and  eventuate  in  a  chronic  Bright's  disease.  In  other  cases 
the  kidneys  are  functionally  normal,  but  are  rendered  more  susceptible 
to  subsequent  burdens  or  infections. 

Various  cutaneous  diseases,  such  as  furuncles,  eczema,  etc.,  may 
follow  in  the  wake  of  scarlatina. 

Reference  has  already  been  m4de  to  certain  psychic  disturbances, 
such  as  mania  and  melancholia,  which  may  persist  after  scarlatina. 

Chorea. — Chorea  may  develop  a  few  months  after  convalescence  is 
established.  This  sequel  is  not  of  great  frequency.  Carlslaw  reports 
only  3  cases  of  chorea  following  533  cases  of  scarlet  fever,  and  Priestley^ 
13  cases  after  5355  attacks  of  scarlet  fever. 

THE  BACTERIOLOGY  OF  SCARLET  FEVER. 

Within  the  past  quarter  of  a  century  numerous  investigations  have 
been  undertaken  to  discover  the  specific  cause  of  scarlet  fever.  That 
the  disease  is  produced  by  a  contagium  vivum  and  that  every  case  of 
scarlet  fever  receives  its  infection  from  a  previous  one  are  propositions 
which  command  general  acquiescence. 

The  exciting  cause  of  the  disease  is  certainly  micro-organismal,  but 
the  identification  of  the  causal  parasite  is  still  shrouded  in  mystery. 

As  early  as  1762,  Plenciz,^  of  Vienna,  attributed  the  cause  of  scar- 
latina to  living  corpuscles.    Hallier^  in  1869  was  one  of  the  first  observers 

1  British  Medical  Journal,  September,  1897,  p.  805. 

2  Quoted  by  Berg6,  loo.  cit.  s  Jahrbuch  f.  Kinderh.,  N.  F.,  ii.,  1868,  1869. 


TIII<:  liACTKh'IOr/XlY  OF  SCARIJ'/r  F/'JV/'Jk  431 

to  search  for  the  microscopic  cause  of  the  disease.  With  the  crude 
magnifying  lenses  at  liis  disposal  he  found  a  micrococcus  in  and  about 
the  blood  corj)usclcs  wliicfi  lie  ref^arded  as  the  morbific  agent  of  the 
disease. 

One  year  later  lloilinan  examined  the  sweat  of  scarlatina  patients 
and  discovered  the  presence  of  a  micrococcus. 

In  1872  Coze  and  Felt//  found  in  the  blood  of  scarlet-fever  patients 
bacteria  G  microns  long,  which  caused  the  death  of  nibbits  when  inocu- 
lated. 

Riess^  in  1S72  found  certain  alleged  lower  forms  of  life  in  the  blood, 
but  failed  to  prove  anything  by  cultures  or  inoculations. 

In  1875  Klebs  found,  in  the  substance  of  an  inguinal  glanrl  of  a 
patient  suffering  from  scarlet  fever,  a  sphere  made  up  of  micrococci 
which  later  changed  their  form.  To  this  organism  he  gave  the  name 
"monas  scarlatinosum." 

Tschamer^  in  1879  claimed  that  scarlatina  was  caused  by  a  crypto- 
gamic  organism,  designated  by  him  the  "verticillium  candelabrum," 
which  is  foimd  upon  rotten  wood.  He  regarded  this  as  one  stage  of 
development  of  the  micrococci  found  by  him  in  the  blood  cells,  scales, 
and  urine. 

In  1882  Eklund*  found  bodies  in  the  urine  of  scarlet-fever  patients 
which  he  called  "plax  scindens."  He  found  similar  organisms  in  the 
soil,  in  water,  and  on  mouldy  walls.  Children  living  in  the  vicinity  of 
such  excavated  soil  were  observed  to  contract  scarlatina. 

Octerlony  observed  these  same  bodies  in  the  blood  and  urine  of 
scarlatina  patients. 

In  1883  Pohl-Pincus^  found  cocci  in  the  epidermic  scales  and  also 
on  the  soft  palate. 

Klamann*^  made  similar  observations  in  the  same  year. 

In  1885  Fraenkel  and  Freudenberg^  isolated  a  streptococcus  from 
the  liver,  kidney,  and  spleen  in  three  fatal  cases  of  scarlet  fever. 

Babes  found  in  18  out  of  20  fatal  cases  of  scarlet  fever  a  strepto- 
coccus which  he  regarded  as  a  variety  of  the  streptococcus  pyogenes." 

Loeffler  in  1884  isolated  the  streptococcus  from  false  membrane  in 
the  throats  of  scarlatinal  patients. 

In  1885  Power^  noted  a  severe  epidemic  of  scarlet  fever  in  London 
which  began  among  the  patrons  of  the  Hendon  farm  who  were  receiving 
milk  from  cows  which  were  suffering  from  a  peculiar  disease. 

Klein^°  investigated  the  circumstances  of  the  epidemic.  He  found  that 
the  disease  in  the  cows  was  transmitted  from  one  to  another,  and  that 

1  Recherches  cliniques  et  exporimentelles  sur  les  mal.  infect.,  Paris,  1S72. 

-  Quoted  by  Bourges,  Les  recherches  microbiennes  dans  la  scarlatine,  Gaz.  hebdom.  de  med.  et  de 
chir.,  March  28,  1891. 

a  Centralz.  f.  Kiuderh.,  1878,  1879,  ii.  *  Quoted  by  Bourges. 

'  Centrablatt  f.  die  med.  Wissen.,  1883,  xxi.  «  Allgemeine  med.  Centralz..  1SS3,  lii. 

7  Quoted  by  Berg6,  Pathog(§nie  de  la  scarlatine,  Paris,  1895. 

s  Quoted  by  Berg6. 

9  Milk  Scarlatina,  Loudon,  Report  of  the  Medical  Officer  of  Local  Government  Board,  Febmarv. 
1885,  1886. 
10  The  Etiology  of  Scarlatina,  Proceedings  of  the  Royal  Society  of  London,  1887,  xlii. 


432  SCARLET  FEVER 

it  began  with  fever,  followed  in  two  or  three  days  by  swelling  of  the 
eyes.  From  the  fourth  to  the  sixth  day  there  appeared  an  erup- 
tion, oculonasal  catarrh,  cough,  and  rapid  breathing.  Desquamation 
occurred  about  the  third  or  fourth  week,  with  loss  of  hair.  In  severe 
cases  sore  throat  and  enlargement  of  the  submaxillary  glands  were 
present.  On  the  fifth  or  sixth  days  several  vesicles  appeared  upon  the 
udders,  which  dried  into  crusts  and  fell  off  about  the  fifth  or  sixth 
week.  Diplococci  sometimes  arranged  as  streptococci  were  found 
in  these  lesions.  Klein,  in  studying  the  blood  of  scarlatina  patients, 
found  from  the  fourth  to  the  sixth  day  of  the  disease,  in  4  out  of  11 
cases,  a  streptococcus  of  the  same  character  as  that  obtained  from 
the  Hendon  cows.  He  regarded  this  as  the  cause  of  the  disease,  and 
looked  upon  the  disorder  in  the  cows  as  bovine  scarlatina. 

Klein's  conclusions  were  attacked  by  Duclaux,  by  C.  B.  Brown,  and 
also  by  Crookshank.  Crookshank^  saw  an  analogous  epidemic  among 
cows  in  Wiltshire  from  which  no  scarlet  fever  was  spread.  The  disease 
was  recognized  by  him  as  cowpox.  Both  Crookshank  and  Thin  con- 
tended that  the  streptococcus  found  by  Klein  was  the  ordinary  strepto- 
coccus of  suppuration. 

In  1887,  Edington,^  working  with  Jamieson,  isolated  from  the  scales 
and  blood  of  scarlet-fever  patients  a  bacillus  which  he  regarded  as  the 
cause  of  the  disease.  The  organism  was  quite  uniformly  found  in  the 
blood  after  the  third  day  and  in  the  scales  after  three  weeks.  This 
so-called  bacillus  scarlatinse  was  motile,  grew  in  long  threads,  and 
fluidified  gelatin.  Inoculations  of  rabbits  and  guinea-pigs  produced 
fever  and  an  erythema  followed  by  desquamation. 

Brown  later  demonstrated  this  bacillus  in  the  scales  of  ordinary 
dermatitis.  A  committee  of  the  Medico-Chirurgical  Society  of  Edin- 
burgh investigated  the  claims  of  Jamieson  and  Edington,  and  was 
able  to  find  the  bacillus  in  but  3  of  10  cases  of  scarlet  fever;  of  nine 
blood  cultures  results  were  obtained  in  four;  cultures  from  scales  were 
negative  and  inoculation  experiments  were  without  result. 

In  1889  Madame  Raskin'  read  before  the  St.  Petersburg  Congress  a 
communication  in  which  she  described  a  peculiar  micrococcus  which 
was  found  in  the  blood  cells  at  the  beginning  of  scarlet  fever.  It  was 
likewise  discoverable  in  the  internal  organs,  skin,  and  mouth  at  autopsy. 
It  killed  rabbits  and  guinea-pigs,  but  did  not  induce  symptoms  of 
scarlet  fever. 

In  1893,  Fiessinger^  announced  his  belief  that  the  streptococcus  was 
the  cause  of  scarlet  fever. 

Dowson^  in  the  same  year  expressed  the  opinion  that  scarlet  fever 
was  due  to  the  streptococcus  and  that  the  tonsil  was  the  seat  of  the 
primary  infection. 

This  assumption  was  later  championed  by  Berge  and  by  Eemoine. 

1  Communication  to  thie  Pathological  Society  of  London,  1887. 

2  Jamieson  and  Edington,  British  Medical  Journal,  1887,  i. 

3  Centralblatt  f.  Bakt.  u.  Parasit.,  1889,  v.  ••  Semaine  m^d.,  July,  1893. 
6  Med.  Chron.,  Manchester,  1893, 1894,  xix.  p.  217. 


77//';  HAdTFjaoinaY  of  hcaulht  f/':vi':r  433 

Bergd/  in  a  l)rocliurc  pul)li.she(l  in  1S95,  disfMisses  at  length  the  njitiire 
of  scarlet  fever  and  fonnnlates  the  following  conclu.sions: 

1.  Ordinary  scarlatina  is  a  local  infection  of  the  tonsils.  The  scarla- 
tinal enij)tion  (exiuithern  and  enjinthem)  is  the  resnlt  of  a  toxic  erytheni- 
agenic  action  of  tlie  inicrohic  poisons  secreted  in  the  infeftterl  tonsils. 

2.  An  imposing  array  of  evidence  points  to  the  strc})tococcns  in  one 
of  its  virulent  forms  as  the  pathogenic  agent  of  the  disease. 

Lemoine^  in  ISOf)  likewise  affirmed  his  belief  that  the  streptococcus 
bore  an  etiological  relationship  to  scarlet  fever,  and  that  the  point  r)f 
entrance  of  the  germs  was  the  throat. 

Class'*  in  1S07  described  a  diplococcus,  sometimes  appearing  in 
short  chains,  which  he  found  constantly  in  the  pharynx  in  scarlatina. 
It  was  also  found  in  the  blood,  but  rarely  after  the  first  day  of  the 
disease.  Intravenous  injections  of  this  organism  in  white  swine  were 
said  to  produce  an  aflFection  closely  simulating  scarlet  fever. 

Schamberg  and  Gildersleeve,^  in  a  bacteriological  examination  of  the 
throats  of  100  cases  of  scarlet  fever,  found  the  diplococcus  described 
by  Class  in  but  15  cases.  They  found  that,  while  this  organism  appeared 
as  a  large  diplococcus  when  first  isolated  and  cultivated  on  certain 
media,  it  later  decreased  in  size  to  about  0.6/^,  and  appeared  as  a 
micrococcus,  occurring  singly  and  in  pairs,  with  an  occasional  short 
chain.  The  organism  reacted  upon  the  various  media  in  a  manner 
similar  to  the  ordinary  staphylococci. 

In  1900  Baginsky  and  Sommerfeld^  described  a  streptococcus  almost 
constantly  found  in  the  throat  and  blood  of  scarlet- fever  patients.  This 
organism  sometimes  appeared  in  short  chains  and  in  pairs.  These 
investigators  tentatively  regard  the  streptococcus  as  the  cause  of  the 
disease. 

Protozoa  in  Scarlet  Fever. — In  1887  L.  PfeifFer''  described  protozoa- 
like  bodies  in  the  blood  of  scarlet  fever  and  vaccinia.  The  significance 
of  these  was  not  explained. 

Mallory^  recently  described  certain  bodies  in  the  skin  in  four  cases  of 
scarlet  fever  which  he  regarded  as  stages  in  the  developmental  cycle 
of  a  protozoon.  They  form  a  series  which  are  closely  analogous  to  the 
series  seen  in  the  asexual  development  (schizogony)  of  the  malarial 
parasite,  but  in  addition  there  are  certain  coarsely  reticulated  forms 
which  may  represent  stages  in  sporogony  or  be  due  to  degeneration  of 
the  other  forms. 

These  bodies  found  in  the  skin  fixed  in  Zenker's  fluid  and  stained 
with  eosin  and  methylene  blue  can  be  divided  into  two  groups.  The 
first  group  consists  of    round,  oval,  elongated,  and  lobulated  bodies 

1  La  paUiog&nie  de  la  scarlatine,  Paris,  1895,  p.  126. 

2  Bull,  et  m^m.  Soc.  mM.  des  hop.  de  Paris,  1S95  and  1S96 

'*  New  York  JVIedical  Record,  September,  1899,  p., 330;  Journal  of  the  American  Medic&l  Associa- 
tion, 1900,  vol.  xxxiv..  No.  SI ;  ibid.,  1900,  No.  13,  p.  799. 

■•  Transactions  of  the  Philadelphia  Pathological  Society  ;  also  Medicine,  September,  1904. 

5  Berliner  klin.  Woehenschrift,  1900,  Nos.  27  and  2S,  p.  688. 

0  Zeitschrift  f.  Hygiene,  Bd.  ii.,  1SS7. 

7  Protozoon-like  Bodies  Found  in  Four  Cases  of  Scarlet  Fever,  Journal  of  Medical  Research,  Janu- 
ary, 1904. 

2S 


431  SCARLET  FEVER 

from  two  to  seven  microns  or  more  in  diameter.     Most  of  the  bodies 
seem  to  be  composed  of  a  close-meshed,  finely  granular  reticulum. 

The  second  group  of  bodies  have  a  striking  radiate  structure.  They 
are  found  in  vacuoles  and  in  the  protoplasm  of  epithelial  cells,  and  free 
in  the  lymph  spaces  and  vessels  of  the  corium  just  underneath  the 
epidermis.  These  radiate  bodies  vary  from  four  to  six  microns  in 
diameter.  They  are  usually  spherical,  contain  a  central  round  body 
around  which  are  grouped  ten  to  eighteen  narrow  segments,  which  in 
some  cases  are  united,  but  in  others  are  sharply  separated  laterally  from 
each  other.     Sometimes  the  segments  are  free. 

Mallory  proposes  for  these  bodies  the  name  "cyclaster  scarlatinalis," 
in  consequence  of  the  frequent  wheel  and  star  shapes  of  the  rosettes, 
its  most  distinguishing  characteristic. 

These  bodies  were  found  only  early  in  the  disease,  most  abundantly 
in  the  skin  of  a  boy  who  died  forty-eight  hours  after  the  appearance  of 
the  eruption.  A  number  of  cases  in  the  desquamative  stage  of  the 
disease  were  examined  with  negative  results. 

The  Relation  of  the  Streptococcus  to  Scarlet  Fever.— The  finding 
of  streptococci  in  scarlet  fever  by  Frankel  and  Freudenberg,  Babes, 
Loeffler,  Klein,  Crookshank,  Fiessinger,  Dowson,  Berge,  Lemoine,  and 
Baginsky  and  Sommerfeld  has  already  been  referred  to. 

Lemoine,  in  a  study  of  the  throat  in  117  cases  of  scarlet  fever,  found 
the  streptococcus  alone  in  93  cases  and  present  with  other  bacteria 
in  14  cases. 

In  1900  Baginsky  and  Sommerfeld^  published  the  results  of  a  large 
number  of  bacteriological  examinations  in  scarlet  fever.  In  411  cases 
of  this  disease  streptococci  were  constantly  found  in  the  throat.  In  a 
later  series  of  290  cases  streptococci  were  found  in  285.  In  this  group 
they  were  found  alone  21  times,  with  staphylococci  222  times,  with 
diplococci  25  times,  and  with  diphtheria  organisms  in  mixed  cases  17 
times.    In  701  cases,  therefore,  streptococci  were  absent  but  5  times. 

Pearce^  found  streptococci  alone  or  associated  with  other  organisms 
in  scarlet  fever,  in  abscessed  ears,  in  the  antra  of  Highmore,  in  bron- 
chopneumonia, serofibrinous  pleurisy,  empyema,  acute  mitral  endo- 
carditis, cervical  lymphadenitis,  embolic  abscesses  in  the  lungs  and 
kidneys,  acute  pericarditis,  acute  diphtheritic  endometritis,  etc.  In  11 
cases  of  general  infection  the  streptococcus  was  found  in  9.  Strepto- 
cocci have  been  found  at  autopsy  in  the  heart's  blood,  liver,  kidneys, 
and  other  organs. 

Weaver'  found  streptococci  in  the  tonsils  of  18  cases.  Cultures  from 
the  skin  of  15  cases  disclosed  nothing  of  interest. 

Slawyk*  in  98  fatal  cases  found  bacteria  in  the  blood  of  52;  strepto- 
cocci were  found  39  times,  and  streptococci  and  staphylococci  6  times. 

Hektoen'^  found  streptococci  in  the  blood  of   scarlet-fever  patients, 

1  Berliner  klin.  Wochenschrift,  1900,  Nos.  27  and  28. 

2  Report  of  Boston  City  Hospital,  1899. 

s  Journal  of  the  American  Medical  Association,  1903,  vol.  v.  p.  609. 

■4  Jahresber.  f.  Kinderheil.,  1901.  ^  Journal  of  the  American  Medical  Association. 


77//';  BA(!TI<:iil()l/)(!Y  OF  SCAUfJ-:T  FHVHIi  435 

more  particiiliirly  in  (Ik'  sov(;re  cjisos.  'J'liry  wen;  ahsent,  however,  in 
some  of  tli(^  IVUiil  cas(!.s. 

S('lijunl)er^  and  Gildcrsleevc'  oxiiinincd,  harlcriolof^ically,  tlif  throats 
of  100  patioTils  snflVritif»;  fi-oiii  scarhit  fever.  A  f^reat  vari(;ty  of 
orpjanisins  was  isohitcd.  Strej)toeoeci  were  found  in  SS  rases  and 
staphylococ(;i  in  73.  The  staphylococci  varied  in  pathogenic  power, 
but,  as  a  rule,  killed  rabbits  and  guinea-[)igs  in  a  sliort  time. 

('ultures  were  also  made  from  the  throats  of  100  apf)arently  well 
jKM'Sons  and  from  S2  per  cent,  of  them  stre[)tococci  wen;  f^btained.  A 
number  of  these  were  tested  and  found  to  l)e  as  virulent  as  tho.se  from 
other  sources. 

The  almost  constant  presence  of  streptococci  in  throats  of  scarlet- 
fever  patients  and  their  activity  in  the  production  of  such  complications 
as  otitis  media,  cervical  abscess,  and  endocarditis  have  led  certain 
writers  to  afHrm  their  belief  in  the  streptococcal  origin  of  scarlet  fever. 
Dowson,  Berge,  and  Lemoine  have,  in  recent  years,  particularly  cham- 
pioned this  view.  There  can  be  no  question  as  to  the  constancy  with 
which  the  streptococcus  is  found  in  scarlet-fever  throats,  and  at  autop.sy 
in  the  various  organs  and  tissues.  This  would  constitute  a  strong  argu- 
ment in  favor  of  its  specific  pathogenicity  in  scarlet  fever,  were  it  not 
for  the  frequency  with  which  it  is  found  in  other  infectious  diseases. 
For  instance,  in  smallpox  it  is  scarcely  less  ubiquitous  than  in  scar- 
latina. 

It  is  commonly  found  in  the  late  pustules  of  smallpox,  and  in  many 
of  the  cutaneous  complications,  such  as  boils,  impetigo,  abscesses, 
erysipelas,  gangrene,  etc.  After  death  streptococci  are  found  in  the 
cutaneous  lesions  and  internal  organs  in  nearly  all  cases.  There  would 
appear  to  be  in  many  cases  an  agonal  or  post-mortem  diffusion  of 
streptococci  throughout  the  tissues.  In  40  autopsies  on  smallpox 
patients  made  by  Perkins  and  Pay,  streptococci  were  found  dis- 
tributed throughout  the  body  in  38.  Ewing  found  streptococci  in 
about  90  per  cent,  of  the  skin  lesions  at  autopsy;  he  also  noted  the 
presence  of  streptococci  in  the  blood  after  death  in  every  one  of  29 
cases  examined. 

It  is  evident  from  the  above  and  other  investigations  that  the  strepto- 
coccus is  almost  constantly  found  in  fatal  cases  of  smallpox.  While 
no  one  can  seriously  entertain  the  idea  that  its  role  in  smallpox  is  causal, 
it  is  so  uniformly  present  that  some  writers  believe  it  bears  a  peculiar 
relationship  to  the  disease  differing  from  most  secondary  infections. 

Many  writers  regard  the  smallpox  bacterjiemia  as  the  most  frequent 
cause  of  death  in  smallpox.  Councilman"  says:  "As  a  result  of  the 
study  of  the  disease,  both  by  culture  of  the  lesions  and  organs  and  by 
microscopic  examination  of  the  tissues,  we  are  inclined  to  regard  bac- 
terial infection  as  a  more  important  agent  in  bringing  about  a  fatal 
termination  than  the  specific  parasite The  bacteria   are 

1  A  Bacteriological  Study  of  the  Throals  of  One  Hundred  Cases  of  Scarlet  Fever,  etc.  :  Trausac- 
tions  of  the  Philadelphia  Pathological  Society  ;  also  Medicine,  September,  1901. 
»  Journal  ot  Medical  Research,  February,  1904,  p.  358. 


436  SCARLET  FEVER 

chiefly  streptococci."  Perkins  and  Pay,  and  likewise  Councilman,  sug- 
gest that  the  streptococci  in  smallpox  gain  entrance  to  the  circulation 
through  the  bronchial  and  pulmonary  mucous  membrane. 

It  would  seem  that  the  relationship  of  the  streptococcus  to  scarlet 
fever  and  to  smallpox  is  quite  similar.  It  gives  rise  in  both  to  numerous 
complications  and  not  infrequently  leads  to  a  fatal  termination.  The 
proof  that  it  is  not  the  cause  of  smallpox  is  easy  of  demonstration;  the 
proposition  that  the  streptococcus  bears  no  etiological  relationship  to 
scarlatina  is  more  difficult  to  disprove. 

It  appears  to  us  reasonable  that  in  certain  infectious  diseases,  particu- 
larly scarlatina  and  smallpox,  the  resisting  powers  of  the  tissues  are  so 
weakened  against  the  streptococcus,  that  this  organism  invades  the 
system  and  works  its  noxious  effects. 

Until  the  streptococcus  found  in  scarlet  fever  is  shown  to  possess 
properties  which  trenchantly  distinguish  it  from  other  streptococci,  and 
until  this  disease  is  experimentally  produced  by  inoculation  of  a  pure 
culture  of  such  an  organism,  the  belief  in  the  causal  relationship  of  the 
streptococcus  to  scarlet  fever  cannot  be  maintained. 


THE  PATHOLOGY  OF  SCARLET  FEVER. 

The  Blood. — The  older  writers  contented  themselves  with  a  descrip- 
tion of  the  fluidity,  coagulability,  and  color  of  the  blood.  At  the  present 
day  accurate  methods  are  in  use  which  throw  considerable  light  upon 
the  changes  in  the  circulating  fluid. 

Felsenthal  and  Bernard,  from  a  study  of  the  specific  gravity  of  the 
blood,  conclude  that  it  is  reduced  in  all  cases  of  scarlet  fever.  The 
reduction  in  haemoglobin  is  disproportionately  great  as  compared  with 
that  of  the  specific  gravity. 

Hayem  was  one  of  the  first  writers  to  point  out  a  reduction  in  the 
red  blood  corpuscles  and  an  increase  of  the  leukocytes.  He  also  called 
attention  to  the  frequent  increase  of  fibrin,  especially  in  attacks  accom- 
panied by  bad  throats  and  suppurative  complications. 

Ewing^  states  that  the  gradual  loss  of  red  cells  noted  by  Hayem  has 
been  fully  verified  by  Kotschetkoff,  who  found  a  reduction  to  three 
millions  or  less  in  nearly  every  case.  Zoppert,  on  the  other  hand,  found 
more  than  four  million  corpuscles  in  5  out  of  6  cases.  A  number  of 
other  observers  have  also  found  in  a  considerable  number  of  cases  but 
a  slight  decrease  of  the  red  cells. 

Estimations  of  the  hoBmoglohin  percentage  were  made  by  Widowitz^  in 
14  cases  of  scarlet  fever.  In  all  but  1  the  haemoglobin  was  strikingly 
high  in  the  beginning,  then  falling  until  the  commencement  of  con- 
valescence, when  it  again  increased  in  quantity.  When  nephritis 
develops  a  more  decided  fall  takes  place. 

1  Clinical  Pathology  of  the  Blood,  1901. 

2  Hamoglobingehalt  des  Blutes  Gesunder  und  Krankerkinder ;  Jahrbuch  f.  Kinderh.,  N.  F. 
xxviii.  p.  384. 


77//';  I'ATiioLodv  ()!<'  scMiLhrr  /<■/':]■  f'ju,  437 

Leukocytes.-  'Ili(!  white  cells  have  been  carefully  .studied  by  a 
nurrilxM"  of  iiivcsti<^ji,t()rs,  uotahly  Kot.sclietkfjn'  and  Bowie.  'Jlien;  i.s 
f^eneral  a^eeineiit  as  to  the  uniform  ;i,nd  early  a[)})earance  of  leuko- 
cytosis. 

Kot.schetkoff  .states  that  leukocyto.sis  is  influenced  hy  the  type  of 
the  disease;  mild  cases  show  usujilly  from  10,000  to  20,000  white  cells; 
tnodcrately  severe  cases,  from  20,000  to  .'->0,000  cells;  and  the  severe  an(] 
usually  fatal  cases  from  30 ,000  to  40,000  cells;  in  some  rapidly  fatal  ca.ses 
over  40,000  leukocytes  were  present.  Yet  Rieder's^  cases  seldom  gave 
more  than  20,000  cells,  although  some  were  complicated  and  fatal. 
FelsenthaP  found  in  six  attacks  of  moderate  severity  in  (-liildren  from 
1S,0()0  to  30,000  leukocytes. 

Bowie^  gives  the  results  of  the  careful  and  repeated  examination  of 
167  cases.  He  concludes  that  (1)  practically  all  cases  of  scarlet  fever 
show  leukocytosis;  (2)  the  leukocytosis  begins  in  the  incubation  period, 
very  shortly  after  infection;  it  reaches  its  maximum  at  or  shortly  after 
the  acme  of  the  disease  and  then  gradually  diminishes  to  normal;  {'S)  in 
simple  uncomplicated  cases  the  maximum  is  reached  during  the  first 
week,  and  the  normal  generally  some  time  during  the  first  three  weeks; 
(4)  the  more  severe  the  case,  the  higher  is  the  leukocytosis  and  the 
longer  it  lasts ;  the  milder  the  case,  the  slighter  the  leukocytosis  and  the 
shorter  time  it  lasts;  (5)  a  favorable  case  of  any  variety  of  the  disease 
has  always  a  higher  leukocytosis  than  an  nnfavorable  one  of  the  same 
variety;  (6)  the  temperature  has  no  effect  on  the  leukocytosis.  These 
observations  are  in  complete  accord  with  those  of  Kotschetkoff. 

Differentiation  of  Leukocytes. — Bowie  states  that  the  poly- 
morphonuclear leukocytes  are  increased  relatively  and  absolutely  at 
first,  and  then  fall  to  normal;  the  lymphocytes  act  in  an  inverse  manner. 
In  simple  cases  this  cycle  occurs  within  the  course  of  three  weeks. 
Kotschetkoff  estimates  the  number  of  the  polymorphonuclears  as  vary- 
ing between  85  per  cent,  and  98  per  cent.,  according  to  the  severity  of 
the  disease;  the  highest  point  is  reached  on  the  second  day  of  the  erup- 
tion, a  gradual  diminution  then  occurring.  The  lymphocytes  are  at 
first  diminished,  but  later  increase  to  normal. 

According  to  Bowie,  the  eosinophiles  are  diminished  at  the  onset 
of  the  fever.  In  simple  favorable  cases  a  rapid  increase  then  occurs 
until  the  height  of  the  disease  is  passed,  when  a  gradual  decline  to 
normal  takes  place,  the  latter  occurring  after  the  disappearance  of  the 
leukocytosis. 

The  more  severe  the  case  the  longer  are  the  eosinophiles  subnormal 
before  they  rise  again.  In  fatal  cases  they  never  rise,  but  sink  rapidly 
toward  zero.  Kotschetkoff  says  that  eosinophiles  in  all  but  severe 
cases  are  normal  or  subnormal  at  first;  after  two  or  three  days  they 
steadily  increase,  reaching  a  maximum  of  8  per  cent,  to  15  per  cent, 
in  the  second  or  third  week,  and  then  decline  slowly  to  normal  about 

1  Quoted  by  Ewing,  loc.  cit.  s  Quoted  by  Ewing. 

*  Quoted  by  Ewing. 

*  Leukocytosis  in  Scarlet  Fever,  Journal  of  Pathology  and  Bacteriology,  March,  1902. 


438  SCARLET  FEVER 

the  sixth  week.  The  eosinophiles  may  disappear  early  in  the  disease 
in  cases  which  prove  fatal. 

While  the  above  quoted  results  of  Kotschetkoff  and  Bowie  are  in 
striking  harmony,  certain  other  observers  have  noted  divergent  findings. 
Sevestre/  frorn  an  examination  of  13  cases,  concluded  that  "in  severe 
cases  it  was  found  that  the  percentage  of  the  finely  granular  eosinophiles 
was  always  high,"  and  "in  the  majority  of  cases  examined  the  per- 
centage of  the  coarsely  granular  eosinophiles  was  found  to  be  dimin- 
ished during  the  whole  period  of  the  disease." 

Ewing  says  that  Weiss  found  no  eosinophiles  in  1  case  at  the  height 
of  the  exanthem,  and  Rille  observed  marked  eosinophilia  in  a  fatal 
case;  Bensaude  observed  as  high  as  20  per  cent,  of  eosinophiles  in 
one  instance. 

Influence  of  Temperature,  Rash,  and  Complications. — Kots- 
chetkoff states  that  the  grade  of  the  leukocytosis  depends  upon  the 
severity  of  the  disease,  especially  the  angina,  but  not  upon  the  height 
of  the  temperature.  Complications  such  as  lymphadenitis,  otitis,  and 
nephritis  usually  have  little  effect  on  the  leukocytosis. 

According  to  Bowie,  the  temperature  has  no  effect  on  the  leukocytosis. 
In  complications,  the  leukocytes  go  through  a  cycle  of  events  similar 
in  all  respects  to  that  of  the  primary  fever  as  regards  both  sum-total 
and  differential  leukocytosis,  and  the  same  laws  govern  the  behavior 
of  the  leukocytes  in  both  cases. 

Sevestre  says  that  "complications  such  as  otorrhoea,  rhinorrhcea,  and 
adenitis  tend  to  increase  the  number  of  white  cells."  He  also  states 
that  a  relationship  exists  between  the  leukocytosis  and  the  rash;  the 
former  varies  with  the  severity  of  the  latter,  and  with  the  fading  of  the 
same  the  leukocytes  show  a  marked  diminution  in  number. 

Rieder  and  Turk^  have  noted  a  high  persistent  leukocytosis,  especially 
in  those  cases  followed  by  nephritis  or  other  complications.  Pee^  found 
an  increase  in  the  leukocytes  in  2  cases  during  a  late  adenitis. 

Bowie  believes  that  the  simple  counting  of  the  leukocytes  is  of  but 
little  diagnostic  value.  A  differential  count  may,  however,  be  of  aid, 
for  scarlet  fever  is  one  of  the  few  acute  infections  in  which  one  finds 
an  early  increase  of  the  eosinophile  cells  and  a  persistence  of  the 
increase  for  some  time. 

As  regards  ^prognosis  he  says:  "In  simple,  severe  scarlatina,  if  the 
leukocytosis  be  high  and  rising,  a  favorable  course  may  be  predicted; 
if  it  be  low  and  stationary  a  tedious  course  may  be  expected.  If  the 
eosinophiles  show  a  relative  increase  the  augury  is  good;  if  they  are 
normal  or  subnormal  after  the  first  day  or  two,  then,  in  all  probability, 
the  case  will  be  severe.  The  persistence  of  a  relative  increase  of  the 
eosinophiles  suggests  some  complication,  whereas,  if  they  come  down 
to  normal  in  the  usual  manner,  one  may  be  free  from  anxiety  as  regards 
complications." 

1  St.  Bartholomew's  Hospital  Reports,  1896,  vol.  xxxii.  p.  225  et  seq. 

2  Quoted  by  Ewing.  s  Quoted  by  Ewing. 


MOiaHI)  ANATOMY  OF  SCAh-U'lT  Fl'JVKR  439 


MORBID   ANATOMY  OF   SCARLET   FEVER. 

But  lilUc  iul'ornuitioii  is  obtained  by  {>ost-rii(>rlf]ji  (■xuniiiiutiou  in 
uncomplicated  cases  of  scarlet  fever  that  cannot  be  foretold  by  the 
symj)tc)iniit()l()(jjy  of  tlic  disease.  The  fj;ross  morbid  changes  are  usually 
observed  in  ilie  skin,  tongue,  throat,  and  lyniplialit;  structun;s  of  the 
body.  Indeed,  the  most  uniform  j^ross  alteratifjn  is  a  hyperplasia  of 
all  of  tlic  lymj)hoid  structures  of  the  body. 

After  death  the  eruption  commonly  fades  away  completely  except  in 
those  cases  in  whicli  the  rash  has  been  intense.  In  the  hemorrhagic 
forms  the  |)etecliial  S])ots  will,  of  course,  remain  visible. 

Histological  Changes  in  the  Skin.^ — Tlie  skin  has  been  studied  by 
a  number  of  investigators,  but  principally  by  Klein,  Unna,  and  Pearce. 

Klein^  studied  the  changes  in  the  skin  in  20  cases.  He  found  the 
epidermis  slightly  thickened,  particularly  the  mucous  layer.  Many  of 
the  rete  cells  showed  dividing  nuclei.  Between  the  horny  and  mucous 
strata  were  small  spaces  containing  granules  resembling  micrococci. 

In  the  rete  Malpighii  were  found  lymph  corpuscles  with  deeply  stain- 
ing nuclei.  In  the  corium  the  epithelial  cells  of  the  follicles  and  sweat 
glands  exhibited  an  increase  of  the  nuclei.  The  bloodvessels  were 
distended  by  corpuscles  and  occasionally  by  fibrin.  The  nuclei  of  the 
lymphatics  and  of  the  endothelial  and  muscular  coats  of  the  arteries 
were  increased. 

Neumann^  noted  swelling  of  the  rete  cells  and  elongation  of  the 
prickle  cells,  between  which  was  evident  a  cell  infiltration,  occasionally 
containing  red  blood  corpuscles.  The  bloodvessels  and  lymphatics  were 
dilated.  There  was  slight  cellular  proliferation  around  the  sw^eat  glands, 
hair  follicles,  and  bloodvessels. 

Kaposi^  regards  the  changes  in  the  skin  as  the  result  of  vascular 
congestion  with  moderate  cell  infiltration;  the  papules  and  vesicles 
occasionally  seen  are  due  to  an  excessive  exudation  and  cell  proliferation 
in  the  papillfe  and  in  the  rete  mucosum. 

Unna*  examined  the  skin  of  7  cases  of  scarlet  fever.  His  findings  are 
briefly  as  follows :  There  is  a  marked  wrinkling  of  the  whole  epidermis 
along  with  the  papillary  body,  which  is  due  to  an  overstretching  of  the 
epidermis  by  the  sodden,  engorged  cutis  and  to  subsecjuent  distortion, 
after  excision  of  the  skin,  when  the  cutis  contracts.  The  elasticity  of 
the  cutis  indicates  that  during  life  it  could  not  have  been  the  seat  of 
oedema. 

The  bloodvessels  of  the  true  skin  are  enormously  dilated,  suggesting 
almost  distention  by  artificial  injection.  This  distention,  which  is 
present  even  after  death,  is  the  result  of  a  vascular  paralysis.  White 
blood  corpuscles  are  extremely  scant,  scarcely  more  than  is  found  under 
normal  conditions. 

1  Local  Government  Report,  viii.  24,  London,  1876  ;  quoted  by  Pearce,  loc.  cit. 

2  Med.  Jahrbiicher,  1882,  p.  152. 

3  Path,  und  Therapie  der  Hautkr.,  Vienna,  1899,  p.  243.  *  Loc.  cit.,  p.  629. 


440  SCARLET  FEVER 

No  particular  changes  are  found,  at  the  height  of  the  eruption,  in  the 
prickle  layer.  There  is  absence  of  mitosis,  oedema,  and  of  any  dilatation 
of  the  interepithelial  lymph  spaces.  Mitoses  are  found  first  and  pretty 
numerously  in  the  stage  of  desquamation. 

In  view  of  the  above  findings,  Unna  regards  the  changes  in  the 
scarlet  fever  sisin  as  paralytic  and  not  inflammatory. 

Pearce^  examined  the  skin  in  8  cases  between  the  second  and  sixteenth 
days,  and  1  on  the  thirty-second  day. 

On  the  second  day,  beyond  a  congestion  of  the  bloodvessels  and 
slight  dilatation  of  the  lymphat  cs,  no  changes  were  observed.  In  3 
cases  examined  on  the  third  day,  a  few  leukocytes  and  lymphoid  cells 
were  seen  in  and  grouped  around  smaller  lymphatics  beneath  the  rete 
Malpighii.  From  the  fifth  to  tenth  days  the  most  marked  condition 
was  an  nfiltration  of  the  epithelium  with  polymorphonuclear  leukocytes. 
The  cells  apparently  leave  the  bloodvessels  beneath  the  rete  and  pass 
up  between  the  epithelial  cells  and  collect  in  the  superficial  layers  of 
dead  cells,  with  which  they  are  thrown  off.  In  the  connective  tissue 
beneath  the  epithelium  were  numerous  polynuclear  leukocytes  and  a 
few  plasma  cells.  The  lymphatics  were  widely  dilated  and  contained 
many  leukocytes.  By  the  twelfth  and  sixteenth  days  the  leukocytic 
infiltration  had  nearly  disappeared.  In  a  late  desquamating  case  the 
rete  contained  numerous  mitotic  figures. 

Tongue. — When  death  occurs  early  in  the  course  of  the  disease  the 
enlarged  papillae  may  be  visible  at  post-mortem.  Pearce^  made  a 
microscopic  study  of  the  tongue  in  8  cases,  all  between  the  second  and 
ninth  days. 

The  process  in  the  tongue  is  said  to  be  similar  to  that  in  the  skin, 
but  is  more  marked  and  begins  earlier.  The  chief  changes  consist  of 
a  dilatation  of  the  papillary  bloodvessels  and  lymphatics,  a  leukocytic 
infiltration  of  the  epithehal  layers,  particularly  pronounced  over  the 
papillae,  and  the  presence  of  leukocytes  in  and  around  the  bloodvessels. 
The  polymorphonuclear  leukocytes  wander  between  the  epithelial  cells, 
collect  beneath  the  superficial  epithelium,  with  which  they  are  cast  oft*. 
The  most  pronounced  cell  infiltration  is  seen  between  the  fourth  and 
ninth  days.  Mast-cells  are  increased  in  number  and  plasma  cells  are 
seen  in  small  numbers  about  the  bloodvessels.  Mitoses  in  the  epithelial 
cells  are  frequent.  Pearce  regards  the  process  as  inflammatory  and 
suggests  that  the  exciting  cause  of  the  leukocytic  infiltration  may  be 
a  positive  chemotaxis  excited  by  the  presence  in  the  tissues  of  the 
scarlet-fever  toxin,  or  by  substances  formed  by  its  action  on  the  super- 
ficial epithelial  cells. 

Lymphatic  System. — In  1872  Harley^  studied  the  post-mortem 
changes  in  28  cases  of  scarlet  fever  and  concluded  that  it  was  a  disease 
of  the  lymphatic  system  characterized  by  hyperplasia  of  the  lymph 
glands,   spleen,  tonsils,  liver,  and   other  lymphatic   structures   of  the 

1  Scarlet  Feyer,  its  Bacteriology  and  Gross  and  Minute  Anatomy,  Medical  and  Surgical  Reports  ot 
Boston  City  Hospital,  1899. 

2  Loc.  cit.  3  Med.  Chir.  Trans.,  London,  1872,  Ix.  p.  102. 


MOItBIl)  ANATOMY  OF  S(!AlilJ':T  h'KVKIi  441 

body.  Tie,  thcnvfore,  proposed  to  .substitute  for  the  riaine,  searlet  fever 
{\w.  tenn  lyin|)liatic  fev(^r. 

Then!  eaii  be  no  (loii})t  tliat  proiioiirK;(!(l  liyperplasia  of  \\\c  lyjn{>hoifl 
tissues  is  a  coiistant  {irid  eoiiS})ieiioiJS  aeeoin})aniiiient  of  sc;arlct  fever. 

Pearee'  found  the  mesenteric,  retroperitoneal,  bronchial,  and  tracheal 
glands  enlarged  in  all  cases.  The  superficial  lymph  nodes,  such  as 
the  cervical,  axillary,  and  inguinal,  were  also  found  enlarged.  The 
glands  were  quite  firm,  and,  on  section,  pale  and  watery. 

Klein  and  J'earce  have  both  jnade  histological  studies  of  tlie  glands. 
Klein^  examined  the  lymph  glands  in  8  cases.  The  centres  of  the  glands 
were  transparent  and  composed  of  large  cells  resembling  giant  cells. 
There  were  also  large  cells  with  transparent  vesicular  nuclei.  In  the 
sinuses  were  small  cells  and  also  large  granular  cells,  with  one  or  two 
transparent  nuclei  (endothelial). 

Pearce  studied  the  glands,  including  the  mesenteric,  cervical,  and 
bronchial,  in  20  cases.  The  changes  observed  were  similar  to  those 
seen  in  the  spleen,  but  were  not  present  in  all  cases.  The  bloodvessels 
were  congested,  and  in  3  cases  small  hemorrhages  were  seen.  The 
lymph  sinuses  were  dilated  and  contained  many  large  endothelial  cells 
lyhig  loose  in  their  lumena.  These  cells  were  frequently  observed  to 
be  phagocytic,  containing  a  number  of  disintegrated  lymphoid  cells. 
Plasma  cells,  exhibiting  numerous  mitotic  figures,  were  found  through- 
out the  lymph  nodes. 

Spleen. — The  gross  appearance  of  the  spleen,  according  to  Pearce, 
permits  of  a  classification  into  two  different  groups.  There  is  no  increase 
in  pulp,  but  a  marked  enlargement  of  the  Malpighian  bodies.  In  such 
cases  the  spleen  is  firm,  and  the  capsule  smooth  but  not  tense;  on 
section  there  is  seen  a  dark-reddish  background,  dotted  everwhere 
with  regularly  or  irregularly  enlarged  Malpighian  bodies.  This  con- 
dition was  noted  in  13  out  of  23  cases  examined. 

In  the  other  class  the  splenic  pulp  is  greatly  increased  and  the  Mal- 
pighian bodies  indistinct.  The  spleen  is  then  large  and  soft.  This 
condition  was  seen  in  7  cases,  in  2  of  which,  however,  there  was  enlarge- 
ment of  the  Malpighian  bodies.  In  the  remaining  3  cases  absolutely 
no  change  in  the  gross  appearance  of  the  spleen  was  visible.  The 
differences  described  do  not  seem  to  depend  upon  the  age  of  the  patient, 
the  stage  of  the  disease,  nor  the  intensity  of  the  infection. 

Klein^  noted,  in  8  cases  examined  histologically,  an  enlargement  of 
the  Malpighian  bodies.  A  peculiar  pale  area,  composed  of  endothelial- 
like  cells,  was  observed  in  the  centre  of  the  bodies.  The  intima  of  the 
bloodvessels  exhibited  a  hyaline  degeneration,  at  times  leading  to 
obliteration  of  the  lumen. 

Pearce  made  a  careful  histological  study  of  the  spleen  in  21  cases. 
The  enlargement  of  the  IMalpighian  bodies  was  found  to  be  due  to  a 
central  massing  of  large  endothelial  cells  in  addition  to  the  presence 
of  numerous  plasma  cells.    These  were  abundantly  present  also  around 

1  Loc.  cit.  -  Transactions  of  the  Pathological  Society  of  London,  1S77  ;  quoted  by  Pearce. 

3  Quoted  by  Pearce. 


442  SCARLET  FEVER 

the  bloodvessels,  in  the  lymphatics,  and  along  the  trabeculse.  The 
bloodvessels  were  greatly  congested.  A  peculiar  condition  noted  was  a 
collection  of  cells,  chiefly  plasma  and  lymphoid  cells,  but  occasionally 
also  a  few  leukocytes,  beneath  the  endothelial  lining  of  the  vessels. 

Liver. — The  gross  changes  in  the  liver  are  not  pronounced.  It 
exhibits  usually,  although  by  no  means  constantly,  some  degree  of 
enlargement.  The  consistence  is  ordinarily  less  firm  than  the  normal 
liver.  In  1  case  Pearce  noted  on  the  surface  a  number  of  minute, 
yellowish  areas,  which  were  shown  to  represent  necrotic  foci.  Roger 
observed  in  2  cases  a  number  of  scattered  red  spots  due  to  subcapsular 
ecchymosis,  a  sort  of  purpura  of  the  liver. 

Histologically,  the  changes  in  the  liver  are  those  of  an  acute  febrile 
infectious  disease.  In  22  cases  examined  by  Pearce  the  liver  cells  in 
each  instance  exhibited  the  degenerative  changes  common  to  fevers. 
In  4  cases  distinct  fatty  degeneration  was  noted,  and  in  7  cases  extensive 
fatty  infiltration.  An  infiltration  of  lymphoid  cells  with  a  few  poly- 
morphonuclear leukocytes  was  found  around  the  portal  vessels  in  11 
cases.  A  few  eosinophiles  and  plasma  cells  were  seen,  the  latter  more 
particularly  in  the  bloodvessels.  Phagocytic  endothelial  cells  were  found 
in  the  bloodvessels  in  5  cases.  Focal  necrosis  of  the  liver  was  observed 
in  4  cases.  The  focal  areas  seemed  to  arise  from  endothelial  cells,  derived 
in  part  from  the  capillary  endothelium  of  the  liver,  and,  in  part,  from 
embolism  through  the  portal  circulation  of  cells  originating  in  the 
spleen.  The  changes  are  similar  to  those  described  by  Mallory  as 
frequently  occurring  in  the  liver  in  typhoid  fever. 

Roger  and  Garnier^  made  histological  examinations  of  the  liver  in 
12  cases.  The  changes  described  by  them  are  of  different  types:  one 
series  concerns  the  mesodermic  elements  of  the  liver — leukocytic  infil- 
tration, thickening  of  the  capsule  of  Glisson,  etc.,  inflammation  of  the 
vessels;  the  other  affects  the  epithelial  tissue.  The  first  stage  of  inflam- 
mation in  the  liver  is  leukocytic  infiltration  of  the  portal  spaces.  Later, 
the  epithelial  cells  are  altered;  they  may  merely  show  unequal  coloration 
of  the  nuclei  or  they  may  degenerate  in  considerable  number  around 
the  portal  spaces,  or,  finally,  a  number  only  may  degenerate,  forming 
a  limited  focus  which  may  subsequently  become  infiltrated  with  leuko- 
cytes. At  the  same  time  inflammation  of  the  conjunctive  tissues  may 
increase  and  the  cells  present  may  undergo  hyaline  and  fatty  degen- 
eration or  fatty  infiltration.  When  parenchymatous  hepatitis  is  extensive 
the  interstitial  changes  also  become  pronounced. 

Gastrointestinal  Tract. — The  mucous  membrane  of  the  pharynx, 
tonsils,  and  soft  palate  show,  under  the  microscope,  the  usual  changes 
observed  in  inflammation  of  these  structures. 

Fenwick^  described  changes  in  the  mucous  membrane  of  the  stomach 
analogous  to  the  desquamation  of  the  cutaneous  surface;  in  severe  cases 
there  was  an  absolute  loss  of  epithelium.      In  addition  he  found  a 

1  Des  modifications  anatom.  et  chimiq.  dufoie  dans  la  scarlatine,  Rev.  de  m6d.,  March  10, 1900,  and 
Roger,  Les  maladies  infect.,  p.  1056. 

2  Medico.-Chir.  Trans,  of  London,  1862,  xlvii. 


MOUIill)  ANATOMY  OF  SCARfJ'//'  FFVh'fi  443 

dilatation  of  the  l)loo(lve,ssels  and  a  filling  up  of  the  ga.stric  tii};iil<.s  witli 
a  granular  and  fatty  nuitcrial  and  small  cells. 

Crooke,  in  a  study  of  0  cases,  found  catarrhal  gastritis  in  all,  anrl, 
in  the  severe  cases,  interstitial  and  folhcnhir  gastritis  characteri'/(;d  hy 
hyperplasia  and  necrosis  of  the  lymph  follicles,  and  infiltration  of  the 
muscular  coat  with  round  cells.  Ilesselwarth  found  21  instances  of  severe 
gastroenteritis  among  -SI   autopsies. 

I'earce  examined  the  stomach  histologically  in  6  cases.  In  a  case 
dying  upon  the  second  day  the  surface  of  the  stomach  was  covered 
with  a  thick  layer  of  mucus  and  necrotic  epithelial  cells,  containing 
numerous  leukocytes  and  cocci.  Polymorphonuclear  leukocytes  and 
granular  material  were  found  in  the  tubular  glands,  and  numerous 
plasma  cells  between  the  tubules.  Enlarged  and  altered  lymj>h  nodules 
were  seen  in  the  lower  part  of  the  mucous  membrane;  4  other  cases 
showed  similar  but  less-marked  changes. 

The  intestines  exhibit  changes  very  similar  to  those  seen  in  the  stomach. 
Virchow  described  marked  hyperplasia  and  swelling  of  the  lymph 
follicles.  Crooke  says  that  Peyer's  patches  at  times  look  like  those 
found  in  typhoid  fever  during  the  first  week. 

Bone-marrow.— Pearce^  examined  the  bone-marrow  in  11  cases,  of 
which  2  were  adults.  In  all  the  cases  the  Ijone-marrow  was  very  cellular. 
Giant  cells  and  nucleated  erythrocytes  were  seen  and  eosinophile  cells 
were  found  in  abundance.  Lymphoid  cells  and  neutrophilic  leukocjies 
were  present  in  fair  numbers.  The  principal  cells,  however,  seen  in  all 
cases  were  about  the  size  of  and  closely  resembled  the  plasma  cell.  They 
formed  the  bulk  of  the  cells  found  in  the  bone-marrow. 

Roger^  found  the  bone-marrow  absolutely  normal  in  1  case,  and  in 
another  evidence  of  slight  reaction  of  the  medullary  tissue. 

Heart. — The  cardiac  muscle  suffers  in  scarlet  fever  from  two  chief 
causes- — the  scarlatinal  poison  and,  secondarily,  from  involvement  of 
the  kidneys.  The  most  common  changes  observed  are  cloudy  swelling 
and  fatty  degeneration,  processes  which  are  observed  in  many  infectious 
diseases. 

Romberg^  has  pointed  out  that  the  interstitial  connective  tissue,  as 
well  as  the  myocardial  tissue,  shows  pathological  alteration.  The  muscle 
fibres  are  separated  by  masses  of  cells  and  the  arterial  bloodvessels 
exhibit  distinct  inflammatory  changes. 

Pearce,  in  an  examination  of  9  cases,  demonstrated  fatty  degen- 
eration in  5.  Segmentation  and  fragmentation  of  the  myocardium  were 
observed  in  a  few  instances. 

The  above  changes  doubtless  result  from  the  poison  of  the  disease. 
The  heart  frequently  undergoes  hypertrophy  and  dilatation  as  a  result 
of  a  coexisting  nephritis. 

Friedlander*  states  that  in  children  with  nephritis  the  heart  increases 

1  Loc.  cit.  :  Loc.  cit. 

5  Ueber  die  Erkrankungen  des  Herzmuskels  bei  Typhus  abdom.,  Scharlach  und  Diphtheria; 
Deutsch.  Archiv  f.  klin.  Med.,  Bd.  xlviii.  and  xlix. 
*  Ueber  Herzhypertrophie  ;  Du  Bois-Reymond,  Archiv  f.  Physiolog.,  1891. 


444  SCARLET  FEVER 

in  weight  on  an  average  about  40  per  cent.  Jager  is  of  the  opinion 
that  two-thirds  of  all  cases  of  scarlatinal  nephritis  are  accompanied 
by  cardiac  hypertrophy  and  often  by  dilatation.  When  the  integrity  of 
the  heart  muscle  is  compromised  in  the  earlier  days  of  the  disease  by 
the  fever  and  the  scarlatinal  poison,  it  becomes  unable  to  withstand 
the  increased'  pressure  later  when  the  kidneys  become  involved,  and 
thus  undergoes  dilatation.  Silberman^  explains  the  heart  changes  as 
follows:  (1)  there  is  no  disease  in  which  the  elimination  of  water  is 
so  suddenly  and  enormously  diminished  as  in  scarlatinal  nephritis; 
(2)  the  glomeruli  are  principally  affected;  (3)  there  is  extensive  involve- 
ment of  the  kidney  structure;  (4)  the  oedema  compresses  the  blood- 
vessels of  the  skin  and  in  this  way  increases  heart  pressure ;  (5)  increased 
resistance  in  the  aortic  system  is  more  readily  followed  by  cardiac 
hypertrophy  in  children  than  in  adults. 

RiegeP  states  that  increased  arterial  tension  accompanies  all  cases  of 
scarlatinal  nephritis,  and  as  a  result  thereof  hypertrophy  of  the  heart 
takes  place.  The  enlargement  is  sometimes  observed  a  few  days  after 
the  development  of  the  nephritis.  Forchheimer  believes  that  from  the 
effects  of  the  scarlatinal  toxin  dilatation  commonly  takes  place,  even 
if  lasting  only  a  short  time,  with  hypertrophy  following  as  compensa- 
tory. 

A  clinically  demonstrable  pericarditis  is  distinctly  uncommon  in 
scarlet  fever.  Slight  grades  of  pericardial  inflammation  are  occasionally 
seen  at  autopsy.  When  nephritis  is  present  effusion  of  serum  often 
occurs,  in  some  cases  giving  rise  to  enormous  distention  of  the  peri- 
cardial sac.  When  inflammation  is  present  the  exudate  may  be  sero- 
fibrinous or  purulent;  in  the  latter  event  streptococci  and  staphylococci 
are  usually  found  upon  culture. 

Endocarditis. — Endocarditis  of  the  cardiac  wall  is  said  by  von 
Jiirgensen,'^  to  be  more  common  than  valvular  endocarditis.  Forch- 
heimer considers  endocarditis  as  a  very  common  complication  of  scarlet 
fever.  The  margins  of  the  valvular  segments  are,  in  mild  cases,  the 
seat  of  small  excrescences,  in  severe  cases  larger  ones  constituting  a 
verrucous  endocarditis. 

Roger  in  2213  personal  examinations,  of  which  1727  were  in  adults, 
observed  endocarditis  but  twice,  while  extracardiac  murmurs  were 
found  692  times.  In  1  of  the  cases  of  endocarditis  there  were  ulcero- 
vegetating  lesions  and  an  abscess  of  the  myocardium.  The  strepto- 
coccus was  found  to  be  the  cause  of  the  abscess. 

Antra  of  Highmore. — Pearce  found  an  inflammation  of  these  cavities 
in  3  cases.  In  2  both  cavities  were  filled  with  an  abundant  purulent 
fluid,  and  the  process  was  a  true  empyema.  In  both  of  these  cases 
both  middle  ears  were  infected,  and  in  one  of  them  the  sphenoidal  sinus 
was  filled  with  a  greenish-yellow  pus. 

1  Jahrbuch  f.  Kinderheilk.,  N.  F.,  1894,  xxxvii. ;  quoted  by  Forchheimer,  loc.  clt. 

2  Ueber  die  Veranderungen  des  Herzens  u.  des  Gefassystems  bei  Acuter  Nephritis ;  Zeitschr.  f. 
klin.  Med.,  1884,  Bd.  vii. 

3  Log.  cit. 


MORIill)  ANATOMY  Oh'  SCAUfJ'/I'  F/'JVKR  445 

Pulmonary  Complication. — In  a  series  of  23  autopsies  Pearce  fourxl 
hronckopyummonia  in  S  eases,  usually  in  the  form  of  small,  discrete 
noduUss,  scattered  alonfr  the  })aek  or  base  of  the  lung.  In  2  cases  the 
process  was  confluent,  involvin<(  tiu;  greater  [)ortion  of  one  or  more 
lobules.  In  5  of  these  cases  both  tiie  strej)toeoccus  and  the  staphylo- 
coccus aureus  were  found.  In  I  case  the  latter  was  found  associated 
with  the  pneumococcus;  in  1  case  the  streptococcus  was  founfl  alone. 

A  fierojihriiious  fleurisy  was  noted  in  1  case  as  the  result  of  strepto- 
coccus infection,  and  in  another  an  em])yema  witli  atelectasis  of  the 
lung.  In  the  latter  a  small  abscess  cavity  was  found  on  the  surface 
of  the  lung. 

Kidneys. — A  voluminous  and  somewhat  confusing  literature  has 
accumulated  upon  the  sul)ject  of  scarlatinal  nephritis. 

Klebs,  in  1870,  was  one  of  the  earliest  writers  to  call  attention  to  a 
glomerulonephritis  occurring  during  convalescence  from  scarlet  fever. 
He  divided  the  kidney  alterations  into  three  groups:  (1)  a  granular 
desquamation  of  the  epithelium  in  the  febrile  stage;  (2)  an  interstitial 
nephritis  frequently  seen  late  in  the  disease;  the  kidney  in  this  condition 
is  large,  lax,  smooth  on  section  and  shows  grayish-w'hite  nodules;  (3) 
a  glomerulonephritis  during  convalescence. 

In  1883,  Friedlander,  from  a  careful  study  of  the  kidney  in  229 
autopsies,  divided  scarlatinal  nephritis  into  three  classes:  (1)  an  early 
catarrhal  nephritis,  occurring  during  the  first  week;  (2)  an  interstitial 
nephritis  in  which  the  kidney  is  large,  white,  and  hemorrhagic;  this 
form  occurs  in  severe  cases  with  bad  throats  and  other  septic  com- 
plications; and  (3)  an  acute  glomerulonephritis  which  develops  during 
convalescence.  The  latter  condition  occurred  in  42  cases  and  was 
egarded  by  Friedlander  as  the  most  characteristic  kidney  'esion  of 
scarlet  fever.  In  this  condition  the  interstitial  tissue  is  practically 
normal,  the  glomeruli  being  solely  involved. 

Councilman  in  1897  characterized  the  condition  of  the  kidney  in 
3  cases  of  scarlet  fever  as  a  pure  interstitial  nephritis.  He  states  ihat 
glomerular  nephritis  occurs  chiefly  in  measles,  acute  endocarditis  and 
diphtheria,  and  acute  non-suppurative  interstitial  nephritis  in  diph- 
theria and  scarlet  fever.  In  the  latter  disease  the  kidney  is  large, 
pale,  and  mottled.  The  principal  lesion  is  an  acute  cellular  infiltration 
with  a  few  phagocytic  endothelial  cells  and  leukocytes.  The  origin  of 
the  plasma  cells  is  presumed  to  be  lymphoid  cells  which  have  undergone 
conversion  in  the  spleen,  and  which  emigrate  from  the  bloodvessels 
and  undergo  mitotic  change  in  the  kidneys. 

Pearce,^  in  a  study  of  23  cases,  found  degenerative  changes  in  all. 
Of  8  specimens  examined  in  the  fresh  state,  6  showed  a  more  or 
less  marked  fatty  degeneration.  Acute  interstitial  nephritis  was  the 
most  important  lesion  present.  In  4  cases  this  process  was  extensive 
and  in  5  slight.  In  the  former  the  cellular  infiltration  was  most  marked 
in  the  cortex  just  beneath  the  capsule,  around  the  glomeruli  and  around 

'  Loc.  cit. 


446  SCARLET  FEVER 

the  bloodvessels  in  the  intermediate  zone.  The  cellular  areas  were 
made  chiefly  of  plasma  cells  with  a  few  lymphoid  cells  and  leukocytes. 
The  glomeruli  were  unaffected.  These  cases  were  fatal  on  the  e  ghth, 
ninth,  fourteenth,  and  fifteenth  days  respectively. 

From  the  writings  of  various  authors  it  is  seen  that  a  considerable 
difference  of  Opinion  exists  as  to  the  most  characteristic  kidney  changes 
in  scarlet  fever.  Councilman  expresses  the  view  that  differences  in 
local  resistance  doubtless  influence  the  susceptibility  of  the  various 
structures.  He  believes  that  in  all  serious  lesions  of  the  kidneys  the 
changes  in  some  cases  may  be  principally  in  the  glomeruli,  and  in  others 
in  the  interstitial  connective  tissue.  The  glomerular  lesions  may  be 
accompanied  by  degenerative  alterations  in  the  epithelium  of  the 
tubules,  which  may  or  may  not  be  secondary.  Hyperplasia  of  the 
connective  tissue  cannot  be  regarded  as  secondary  to  tubular  changes. 

Certain  investigators,  particularly  Marie,  Haskine,  Guinon,  and 
Babes  have  found  streptococci  in  nearly  all  forms  of  scarlatinal  nephritis. 
How  far  the  inflammatory  changes  are  due  to  such  micro-organisms 
and  to  what  extent  the  scarlatinal  toxin  is  responsible,  time  and  future 
research  must  determine. 


CHAl'TKR    VIII. 

SCARLET  FEVER.  {Continued). 
THE    DIAGNOSIS    OF    SCARLET    FEVER. 

When  scarlet  fever  exhibits  itself  in  a  prononnccd  mid  typifjil  forin 
the  (lia<i;iio,sis  is  very  simple.  As  is  the  case  with  all  diseases,  however, 
aberrant  and  uinisnal  cases  cpiite  frecjuently  })resent  themselves,  in 
which  circumstance  the  establishing  of  the  nature  of  the  disease  offers 
the  most  perplexing  difficulties. 

We  are  of  the  belief  that  more  errors  of  diagnosis  are  made  in  con- 
nection with  scarlet  fever  than  with  any  other  acute  disease.  On  the 
one  hand,  many  cases  of  extremely  mild  scarlet  fever  are  overlooked, 
and,  on  the  other  hand,  rashes  from  other  causes  resembling  that  of 
scarlatina  are  not  infrequently  diagnosed  as  the  latter  disease. 

It  should  be  remembered  that  there  is  no  one  symptom  of  scarlatina 
which  is  pathognomonic  of  the  disease.  The  rash,  the  most  conspicuous 
symptom  and  the  one  which  has  given  the  affection  its  name,  is  not 
in  itself  characteristic,  inasmuch  as  an  almost  identical  exanthem 
may  occur  in  other  conditions.  Nor  does  its  absence  entirely  exclude 
the  diagnosis  of  scarlet  fever.  Indeed,  we  may  have  a  scarlet  fever 
without  eruption,  scarlatina  sine  eruptione;  without  fever,  scarlatina  sine 
febre;  or  without  sore  throat,  scarlatina  sine  angina. 

When  all  of  the  symptoms  of  scarlet  fever  are  developed  an  unmistak- 
able syndrome  is  presented.  Who  could  fail  to  diagnose  a  disease 
characterized  by  sudden  vomiting,  high  fever,  prostration,  diffuse 
punctiform  rash,  circumoral  pallor,  red  and  swollen  throat,  enlarged 
glands,  strawberry  tongue,  followed  by  desquamation  and  albuminuria  ? 
But,  unfortunately,  this  picture  is  often  incomplete.  Those  who  have 
had  experience  with  scarlet  fever  have  observed  that  in  severe  cases 
the  various  symptoms  are  usually  well  pronounced,  whereas  in  mikl 
cases  all  of  the  symptoms  are  commonly  poorly  marked.  When  the 
eruption  is  intense  the  throat  is  usually  severely  attacked,  the  tongue 
is  characteristic,  and  the  fever  is  high.  When,  on  the  other  hand,  the 
general  symptoms  are  very  mild  the  rash  is,  as  a  rule,  faint  or  poorly 
developed.  It  is  under  the  latter  circumstances  that  the  diagnosis 
becomes  so  difficult,  for  the  complex  of  symptoms  upon  which  the 
foundation  of  the  diagnosis  rests  is  too  weak  to  support  it. 

How  often  do  we  see  cases  in  which  the  rash  is  faint,  the  constitu- 
tional symptoms  mild,  and  the  throat  and  tongue  uncharacteristic  I 
The  evidence  appears  very  slender  upon  which  to  base  the  diagnosis 
of  a  disease  w^hich  necessitates  two  or  more  months  of  isolation.  Under 
these  circumstances  the  physician  will  do  best  to  postpone  the  pro- 


448  SCARLET  FEVER 

nouncement  of  a  diagnosis  until  the  further  course  of  the  disease  is 
watched.  In  some  cases  it  remains  impossible  to  be  sure  of  the  scar- 
latinous nature  of  the  disease. 

Etiological  Evidence. — The  diagnosis  in  cases  of  scarlet  fever  with 
obscure  symptoms  is  often  simplified  by  the  discovery  of  the  disease 
in  a  person  to  whom  the  patient  has  been  exposed.  In  institutions  for 
children  the  existence  of  an  epidemic  often  clarifies  an  individual 
diagnosis  which  would  be  quite  impossible  to  make  under  other  circum- 
stances. Close  enquiry  and  examination  will  sometimes  discover  a 
desquamating  and  hitherto  unrecognized  case  of  scarlet  fever  to  be  the 
origin  of  an  institution  epidemic. 

The  diagnosis  of  scarlet  fever  in  doubtful  cases  is  sometimes  con- 
firmed by  the  disease  being  transmitted  by  the  suspected  patient  to 
another  person. 

Diagnostic  Value  of  the  So-called  Strawberry  Tongue. — In  the  very 
beginning  the  tongue  in  scarlet  fever  is  heavily  coated  with  a  whitish 
fur  through  which  scattered  red  papillte  are  frequently  visible.  In 
about  forty-eight  hours  the  coating  peels  off  and  there  is  seen  a  red 
tongue  studded  with  enlarged  papillae.  This  condition  of  the  tongue 
is  certainly  a  symptom  of  considerable  diagnostic  importance,  and  its 
presence  or  absence  in  doubtful  cases  should  be  determined  and  con- 
sidered in  formulating  the  diagnosis.  But  several  sources  of  error  must 
be  kept  in  view.  In  mild  cases  of  scarlet  fever  in  which  the  rash  and 
general  symptoms  leave  doubt  as  to  the  nature  of  the  disease  the  tongue 
often  fails  to  present  its  characteristic  appearance.  We  cannot  agree 
with  McCollom,  of  Boston,  who  says  that  the  enlargement  of  the  papillae 
is  present  in  every  case  of  scarlet  fever,  if  carefully  looked  for.  We 
have  certainly  seen  a  number  of  children  in  scarlet-fever  wards  whose 
tongues  have  been  quite  normal  in  appearance.  Most  of  these  children 
had  mild  attacks. 

On  the  other  hand,  the  tongue  in  well  persons  shows  a  variable 
amount  of  prominence  of  the  lingual  papillae.  We  have  examined  the 
tongues  of  a  large  number  of  people  with  a  view  of  determining  this 
point.  Anyone  who  repeats  this  experience  may  satisfy  himself  that 
the  tongue  under  normal  conditions  exhibits  wide  variations  in  the  size 
and  prominence  of  the  papillae.  Moreover,  there  are  certain  chronic 
forms  of  superficial  glossitis  in  which  the  papillae  are  quite  large. 

It  must  be  remembered,  too,  that  the  most  typical  strawberry  tongue 
may,  in  rare  cases,  occur  in  affections  other  than  scarlet  fever.  In  a 
few  severe  cases  of  scarlatiniform  erythema,  occurring  during  the  course 
of  smallpox,  we  noted  very  distinct  "strawberry"  tongues. 

However,  these  exceptions  do  not  invalidate  the  force  of  the  state- 
ment that  the  presence  of  pronounced  enlargement  of  the  lingual 
papillae  in  cases  suspected  of  being  scarlet  fever  is  strong  confirmatory 
evidence.  The  negative  value  of  the  absence  of  the  characteristic 
tongue  is  of  less  importance. 

The  Diagnostic  Value  of  Desquamation.— The  statement  is  some- 
times made  that  the  occurrence  of  desquamation  after  a  scarlatiniform 


77//';  i)f  A  GNOSIS  OF  scA/aj'rr  fevkr  451 

This  affection,  if  i(  may  be  called  such,  is  characterized  by  an  eruption 
wlii('h  niiiy  be  (juiie  iiulistinf^ui.sliable  from  that  of  true  scarlet  fever. 
It  may  be  (HiVused  over  the  entire  cutaneons  snrfaee  and  may  be  jjuneti- 
form.  It  is  often  sudden  in  its  onset  and  may  be  attended  witli  mnlaise 
and  moderate  rise  of  temperature  (100°  to  102°  F.j.  (Occasionally  the 
initial  pyrexia  is  higher,  l)ut  under  such  circumstances  it  soon  declines. 
The  throat  may  be  reddened,  but  there  is  no  swelling  of  the  tonsils  and 
usually  no  eoinj)laint  of  sore  throat. 

The  eruption  has  about  the  same  duration  as  that  of  scarlet  fever, 
although  it  is  often  briefer.  It  is  follov^ed  by  a  descjuamation  wliich  is 
ordinarily  branny,  but  which  may  take  place  in  large  flakes. 

Desquamative  scarlatiniform  erythema,  termed  by  some  writers  acute 
exfoliative  dermatitis,  differs  from  the  above  type  in  degree  rather  than 
in  kind. 

It  is  characterized  by  the  appearance  of  an  extensive,  often  puncti- 
form  erythema,  which  rapidly  covers  the  entire  body  and  is  accompanied 
by  more  or  less  febrile  disturbance.  In  the  course  of  three  or  four  days 
the  skin  begins  to  desquamate  profusely,  being  thrown  off  in  large 
lamellae  or  sheets.  Epidermal  casts  of  the  palms  and  soles,  looking  not 
unlike  gloves  or  slippers,  may  be  exfoliated.  The  nails  may  be  lost 
and,  in  severe  cases,  the  hair  also.  Before  the  skin  has  returned  to  its 
normal  condition  a  relapse  may  occur  characterized  by  fever,  erythema, 
and  a  second  desquamation.  In  some  cases  three  or  four  such  relapses 
may  take  place. 

This  type  of  the  disease  is  peculiarly  prone  to  recurrences,  which  may 
appear  every  six  months  or  a  year.  Sometimes  marked  periodicity  is 
exhibited,  the  recurrent  attacks  developing  with  almost  calendar  pre- 
cision. Doubtless  many  of  the  cases  of  scarlet  fever  recorded  in  the 
literature  of  the  subject  which  are  alleged  to  have  recurred  five,  six, 
or  more  times  were  in  reality  cases  of  scarlatiniform  erythema  of  the 
desquamative  type. 

These  eruptions  are  due  to  toxic  or  septic  states  or  to  the  action  of 
drugs  or  sera.  Simple  scarlatiniform  erythema  may  occur  during  the 
course  of  various  infectious  processes,  such  as  rheumatism,  septicaemia 
(puerperal  or  other  forms),  pyaemia,  malaria,  typhoid  fever,  etc.  x^ 
evanescent  scarlatiniform  rash  may  appear  before  the  true  exanthem 
of  measles,  varicella,  smallpox,  and  vaccinia. 

All  grades  of  scarlatiniform  erythema  may  develop  during  the  stage 
of  decrustation  of  smallpox. 

Diphtheria  antitoxin  and  other  sera  may  produce  scarlatiniform 
rashes.  Antitoxin  rashes  developing  in  the  course  of  diphtheria  may, 
in  some  cases,  so  closely  simulate  the  eruption  of  scarlet  fever  as  to 
defy  all  eft'orts  at  satisfactory  differentiation.  Northrup^  very  truly 
says:  "Antitoxin  rashes  are,  at  times,  most  difficult  to  differentiate  from 
scarlet-fever  rashes. 

"At  the  Willard  Parker  Hospital  in  New  York,  where  both  diphtheria 

1  Addenda  to  vou  Jiirgensen's  article  on  Scarlet  Fever,  Nothnagel's  Encyclopedia  of  Practical 
Medicine,  American  edition. 


452  SCARLET  FEVER 

and  scarlet  fever  are  cared  for,  it  has  been  almost  beyond  the  power 
of  experts  to  pronounce  definitely  upon  certain  cases." 

Intestinal  autointoxication  may  give  rise  to  a  scarlatiniform  eruption. 
Crocker  says  this  may  follow  the  use  of  enemata,  which  sometimes 
facilitate  the  solution  and  absorption  of  toxins. 

The  drugs  which  most  commonly  give  rise  to  scarlatiniform  eruptions 
are  quinine,  mercury,  belladonna,  and  salicylic  acid.  Many  other 
medicaments  occasionally  produce  scarlatinoid  rashes  in  susceptible 
subjects.  The  eruption  resulting  from  the  administration  of  quinine  is 
the  most  frequent  and  the  most  likely  to  be  confounded  with  scarlet 
fever.    It  may  be  followed  by  well-marked  desquamation. 

It  is  often  a  matter  of  great  difficulty  to  differentiate  scarlatiniform 
erythema  from  true  scarlet  fever.  In  the  former  the  invasive  symptoms 
are  often  extremely  mild;  the  patient  commonly  does  not  complain  of 
feeling  ill;  the  temperature  elevation  is  slight,  perhaps  101°  or  102°  F. 
The  throat  may  be  reddened,  but  the  tonsils  and  uvula  are  not  swollen 
and  exudate  is  not  present  upon  the  tonsils. 

The  reddened,  papillated  tongue  is,  as  a  rule,  absent.  The  eruption 
may  begin  upon  any  portion  of  the  body;  it  may  be  patchy  and  irregular, 
or  it  may  be  diffuse,  with  or  without  punctation.  The  glands  at  the 
angles  of  the  jaws  are  not  apt  to  exhibit  any  pronounced  enlargement; 
albuminuria  is  rare  and  otitis  media  does  not  occur. 

It  is  thus  seen  that  scarlatiniform  erythema  may  be  readily  distin- 
guished from  a  well-pronounced  attack  of  scarlet  fever;  but  the  fact 
must  not  be  overlooked  that  there  are  many  mild  cases  of  scarlet  fever 
in  which  the  fever  is  slight,  the  eruption  poorly  marked,  and  the  other 
symptoms  correspondingly  uncharacteristic. 

The  significant  feature  in  scarlatiniform  erythema,  particularly  when 
the  rash  is  well  pronounced,  is  that  the  intensity  of  the  eruption  is  out 
of  all  proportion  to  the  amount  of  constitutional  disturbance.  There 
is  not  present  the  prostration  and  high  fever  which  would  accompany 
a  rash  of  similar  severity  in  scarlet  fever.  Furthermore,  there  is  never 
seen  in  scarlatiniform  erythema  a  severe  sore  throat. 

Another  point  of  great  diagnostic  importance  is  the  history  as  to 
previous  attacks;  the  tendency  to  recurrence  is  a  well-recognized  feature 
of  scarlatiniform  erythema. 

We  have  occasionally  had  patients  sent  into  the  Municipal  Hospital 
with  scarlatiniform  erythemata  which  had  been  diagnosed  as  scarlet 
fever.  We  recall  a  young  man  who  presented  a  generalized  scarlatinoid 
eruption  of  moderate  intensity  which  inaugurated  the  onset  of  a  typical 
intermittent  fever.  Another  patient,  a  girl  aged  five  years,  sent  in 
from  a  foster  home,  had  an  eruption  indistinguishg.ble  from  scarlet  fever, 
which  proved  to  be  a  prodromal  chickenpox  eruption;  this  girl  contracted 
a  well-pronounced  scarlet  fever  six  days  after  admission  to  the  scarlet- 
fever  ward. 

A  young  woman,  sent  into  the  hospital  with  an  intense  erythema 
which  was  diagnosed  as  scarlet  fever,  passed  through  an  attack  of 
exfoliative  dermatitis,  with  profuse  desquamation  and  subsequent  loss 


Till']  DIAdNOHH^  OF  SCAIUJCT  FI'JVM/i  453 

of  hair  and  nails.  She  had  previously  received  large  doses  of  antipyrin, 
and  this  (lrn<^  wiis  found  in  the  urine. 

We  liave  n^eently  had  under  ohseivntion  a  young  man,  aged  cigliteen 
years,  who  was  sent  into  the  Municipal  llf>s[)ital  three  times  vdthin  a 
year  with  the  diagno,sis  of  scarlet  fever,  lie  was  admitted  to  the  llos- 
{)ital  first  on  June  li,  1902.  He  had  vomiting,  sore  throat,  slight  fever, 
and  a  generalized  searlatiniform  eruption.  He  desquamated  y)rofusely. 
The  sealing  lasted  almost  nine  w(>eks,  and  the  patient  was  diseliarged 
on  September  8,  1002. 

The  patient  was  readmitted  on  January  9,  1903.  He  had  sore  throat, 
headache,  slight  fever,  and  a  well-marked  searlatiniform  rash.  Slight 
desquamation  occurred  upon  the  face  and  trunk. 

The  patient  was  admitted  for  the  third  time  on  June  28,  1903.  He 
had  had  repeated  vomiting,  headache,  sore  throat,  and  some  fever;  on 
admission  there  was  a  generalized,  well  pronounced  searlatiniform 
eruption,  not  punctated,  however.  The  tongue  was  heavily  coated,  but 
after  this  disappeared  there  w^as  no  enlargement  of  the  papillfe.  Desqua- 
mation was  well  marked,  being  particularly  copious  on  the  hands  and 
feet.  The  latter  were  still  peeling  in  large  lamellae  at  the  end  of  a 
month. 

Each  of  these  attacks  resembled  scarlet  fever  sufficiently  to  cause 
the  resident  physician  to  admit  the  patient. 

We  would  call  attention,  however,  to  the  fact  that  the  fever  and  sore 
throat  on  each  occasion  were  very  slight.  There  was  no  prostration 
and  the  characteristic  tongue  was  absent.  We  have  no  doubt  that  the 
patient  was  suffering  from  a  searlatiniform  erythema,  possibly  due  to 
intestinal  autointoxication. 

Drug  Rashes. — Quinine,  antipyrin,  opium,  belladonna,  chloral,  and 
mercury  at  times  produce  eruptions  which  may  closely  simulate  that 
of  scarlet  fever.  The  eruption  resulting  from  quinine  is  the  most 
frequent  and  the  most  likely  to  be  confounded  with  scarlet  fever.  x\s 
a  rule,  in  these  eruptions  the  constitutional  disturbance  is  dispro- 
portionately slight,  and  severe  sore  throat,  swelling  of  the  glands, 
strawberry  tongue,  and  middle-ear  disease  are  absent.  The  eruption 
often  fails  to  begin  on  the  chest  and  pursue  the  normal  progression 
of  the  scarlatinal  exanthem.  The  occurrence  of  desquamation  has  no 
diagnostic  value  in  these  cases,  as  the  drug  rashes  may  be  followed 
by  a  variable  amount  of  epidermal  exfoliation. 

Measles. — There  is  no  difficulty  in  distinguishing  between  measles 
and  scarlet  fever  under  ordinary  circumstances.  There  are,  however, 
irregular  cases  of  each  disease  in  which  the  elimination  of  the  other  in 
the  diagnosis  is  by  no  means  easy. 

The  rash  in  scarlet  fever  is  now  and  then  blotchy,  especially  upon 
the  extremities;  in  other  cases,  particularly  of  septic  scarlatina,  a  profuse 
rhinorrhoea  may  be  present,  even  early  in  the  course  of  the  disease; 
these  symptoms,  associated  with  an  otherwise  irregular  s^Tnptom- 
complex,  may  produce  quite  a  resemblance  to  measles. 

The  eruption  of  measles  may,  as  a  result  of  coalescence  of  the  macules, 


454  SCARLET  FEVER 

closely  simulate  that  of  scarlet  fever.  In  some  epidemics  the  proportion 
of  confluent  measles  eruptions  appears  to  be  greater  than  in  others. 
A  few  years  ago  during  the  prevalence  of  a  particularly  severe  form  of 
measles,  we  noted  a  frequent  tendency  of  the  exanthem,  after  the  lapse 
of  twenty-four  or  forty-eight  hours,  to  become  confluent  and  present 
the  appearance  of  a  diffuse  scarlatiniform  eruption.  Usually,  however, 
there  may  be  seen  somewhere  on  the  trunk  or  extremities  sharp  margin- 
ation  of  the  eruption  with  contiguous  areas  of  pale,  normal  skin. 

In  measles  the  face  is  earlier  and  more  copiously  affected  than  in 
scarlet  fever;  the  eruption  is  dusky  red  in  color,  palpably  raised  above 
the  skin,  and  distinctly  blotchy;  it  appears  later  than  the  eruption  of 
scarlet  fever  (about  the  fourth  day) ;  there  is  a  prodromal  stage,  during 
which  time  catarrhal  symptoms  affecting  the  eyes,  nose,  larynx,  and 
bronchial  tubes  are  present,  producing  watery  eyes,  sneezing,  running 
nose,  hoarseness,  and  frequent  cough.  The  initial  fever  is  not  as  high 
as  in  scarlatina  and  the  tendency  to  vomiting  is  less.  Sore  throat,  great 
glandular  intumescence,  strawberry  tongue,  lamellar  desquamation, 
and  nephritis,  commonly  seen  in  scarlet  fever,  are  absent  in  measles. 

The  presence  of  Koplik  spots  upon  the  buccal  mucous  membrane 
would  decide  in  favor  of  measles.  The  discovery  of  a  marked  leuko- 
cytosis would,  it  is  claimed,  point  strongly  toward  the  scarlatiniform 
nature  of  the  disease. 

At  times  a  secondary  roseolous  or  measles-like  eruption  appears  later 
in  the  course  of  scarlet  fever.  This  is  regarded  by  Thomas  as  a  pseudo- 
relapse,  but  it  seems  to  us  to  be  of  the  nature  of  a  septic  rash. 

Smallpox. — Scarlet  fever  may  be  confounded  with  the  prodromal 
scarlatiniform  rash  that  is  occasionally  seen  during  the  initial  stage  of 
smallpox.  The  absence  of  angina  and  the  appearance  of  the  variolous 
papules  will  make  the  diagnosis  clear. 

During  the  later  pustular  stage  of  variola  an  intense  scarlatiniform 
eruption  at  times  develops  which  may  raise  the  question  of  a  secondary 
infection  with  scarlet  fever.  There  may  be  high  fever,  prostration, 
and  subsequent  desquamation.  The  absence  of  vomiting,  sore  throat, . 
the  strawberry  tongue,  and  the  development  of  the  eruption  about  the 
twelfth  to  the  fifteenth  day  of  smallpox  will  usually  enable  one  to  recog- 
nize the  character  of  the  rash. 

Influenza. — Influenza  is  sometimes  accompanied  by  a  scarlatiniform 
eruption  which  may  cause  scarlet  fever  to  be  suspected.  The  presence 
of  severe  muscular  pains  and  catarrhal  symptoms,  and  the  absence  of 
the  angina  and  the  characteristic  tongue,  together  with  attention  to 
the  character  of  the  prevailing  epidemic  will  usually  suffice  to  distinguish 
the  two  affections. 

Rubella. — With  the  usual  type  of  rubella  scarlet  fever  scarcely  comes 
into  differential  confiict.  It  is  with  that  form  which  tends  to  present  a 
diffuse  eruption  that  errors  may  arise.     (See  article  on  Rubella.) 

Diphtheria. — Ordinarily  scarlet  fever  and  diphtheria  have  but  little 
in  common,  and  yet  errors  in  diagnosis  are  not  infrequent.  Too  often 
physicians  glance  into  the  throat,  see  exudate  present  upon  the  tonsils, 


THE  DTACJNOSrS  OF  SCARLET  FEVER  4.55 

and  perhaps  iij)()ii  tlie  soft  pnlatc,  and  straightway  make  the  diagnosis 
of  (lipl)theria.  Time  and  time  again  liave  w(;  received  calls  at  the 
Municipal  Hospital  for  cases  of  diphtheria,  only  to  discover  on  seeing 
the  patient  the  presence  of  a  scarlatinal  rash.  l)ij)htheri;i  is  ordinarily 
not  accom])anied  by  an  exanthem. 

Vomiting  is  nnich  more  common  as  an  invnsive  sym{>tfjm  of  scarlet 
fever  than  of  diphtheria.  The  exudate  in  diphtheria  is  tough  and  thick, 
of  a  grayish  or  grayish-yellow  color,  and  quite  firmly  adherent  to  the 
underlying  mucous  membrane.  That  of  scarlet  fever  is  yellowish,  thin 
and  smeary,  and  more  easily  wiped  off.  In  scarlet  fever,  moreover,  the 
tln-oat  ordinarily  shows  more  intense  redness  and  oedema  than  in 
diphtheria.  The  soft  palate  commonly  presents  a  punctated,  reddened 
appearance. 

Enlargement  of  the  maxillary  and  submaxillary  glands  occurs  in  both 
diseases.  The  temperature  in  diphtheria  tends  to  subside  in  a  few  days; 
in  scarlet  fever  it  commonly  persists  for  a  longer  period.  The  straw- 
berry tongue  of  scarlatina  is  absent  in  diphtheria. 

Otitis  media  may  occur  in  both  diseases,  but  it  is  more  common  in 
scarlet  fever.  Albuminuria  is  an  early  symptom  in  diphtheria  and  a 
late  symptom  in  scarlet  fever.  It  is  present  in  about  one-half  or  more 
of  the  cases  of  diphtheria  and  is  commonly  found  on  the  third  or  fourth 
day.  A  transient  albuminuria  may  occur  early  in  severe  cases  of  scarla- 
tina accompanied  by  high  fever,  but  the  true  scarlatinal  nephritis  is  ordi- 
narily discovered  about  the  end  of  the  third  week.  The  early  albuminuria 
of  diphtheria  is  apt  to  be  associated  with  the  presence  of  tube  casts. 

While  the  finding  of  Klebs-LoefHer  bacilli  in  the  throat  is  of  great 
diagnostic  importance,  their  presence  does  not  exclude  scarlet  fever. 
At  the  Municipal  Hospital  we  have  cultures  made  of  all  scarlet-fever 
patients  on  admission  to  the  hospital.  The  percentage  of  cases  in  which 
diphtheria  bacilli  have  been  found  varies  from  time  to  time.  It  has 
been  as  low  as  8  in  100  and  as  high  as  30  in  100.  It  is  by  no  means 
always  the  bad  throats  that  give  positive  cultures.  In  many  of  the 
cases  in  which  the  Klebs-LoefHer  bacilli  are  found  there  is  no  exudate 
at  all  in  the  throat. 

That  diphtheria  and  scarlet  fever  may  occur  at  the  same  time  is 
generally  admitted.  In  our  experience  scarlet  fever  has  more  often 
developed  in  the  course  of  diphtheria  than  the  reverse.  Diphtheria 
is  more  apt  to  appear  after  the  acute  symptoms  of  scarlatina  have 
subsided.  Scarlet  fever,  on  the  other  hand,  not  infrequently  makes  its 
appearance  early  in  the  course  of  diphtheria. 

To  distinguish  between  the  scarlatiniforin  rash  that  occasionally 
occurs  in  diphtheria  and  a  true  complicating  scarlet  fever  is  a  most 
difficult  and,  indeed,  an  often  impossible  task.  Clinicians  of  experience 
recognize  this  fact.  Osier,  for  example,  says:  "Scarlet  fever  and  diph- 
theria may  coexist,  but  in  a  case  presenting  widespread  erythema  and 
extensive  membranous  angina,  with  Loeffler's  bacillus,  it  would  puzzle 
Hippocrates  to  say  whether  the  two  diseases  coexisted,  or  whether  it 
was  only  an  intense  scarlatinal  rash  in  diphtheria." 


456  SCARLET  FEVER 

It  has  been  our  custom  to  regard  as  a  complicating  scarlet  fever  any 
well-pronounced  scarlatiniform  rash  accompanied  by  distinct  elevation 
of  temperature;  if  vomiting  occur  and  the  lingual  papillae  become 
enlarged  the  diagnosis  is  much  clearer.  We  have  sent  all  such  cases 
to  a  mixed  ward  in  which  there  have  been  undoubted  cases  of  scarlet 
fever,  and  it  has  been  extremely  rare  for  any  children  thus  transferred 
to  contract  scarlet  fever.  We  have  never  seen  an  intense,  well-pro- 
nounced scarlatiniform  rash  in  diphtheria  that  we  felt  could  be  regarded 
as  an  erythema  diphtheriticum. 

Since  the  introduction  of  the  use  of  diphtheria  antitoxin  the  difficulties 
of  diagnosis  have  been  increased,  for  a  third  possibility  presents  itself, 
namely,  a  scarlatiniform  antitoxin  rash. 

The  occurrence  of  scarlatiniform  eruptions  in  diphtheria  wards  is 
always  a  source  of  anxiety.  If  the  patient  is  allowed  to  remain,  other 
children  may  be  exposed  to  scarlet  fever;  if,  on  the  other  hand,  the 
patient  is  transferred  to  a  mixed  ward,  there  is  a  risk  of  his  contracting 
scarlet  fever.  It  is  well  to  have  nearby  a  number  of  small  rooms  in 
which  patients  may  be  placed  for  a  few  days  and  watched.  These  cases 
tax  the  diagnostic  acumen  of  even  the  most  experienced  physicians. 

Tonsillitis. — ^An  inflammation  and  enlargement  of  the  tonsils  with 
the  development  of  exudate  in  the  crypts  is  so  often  seen  in  scarlet 
fever  as  to  constitute  a  part  of  the  symptom-complex  of  this  disease. 
It  is  recognized  that  scarlatina  may  occur  without  an  exanthem.  The 
determination  of  the  scarlatinal  character  of  a  tonsillitis  occurring 
in  a  person  exposed  to  the  infection  of  scarlet  fever  is  a  most  difficult 
matter.  If  the  exposure  has  been  intimate,  the  individual  unprotected 
by  previous  attack  of  scarlet  fever,  the  characteristic  tongue  appearance 
and  the  angina  present,  and  otitis  media  or  nephritis  develop,  the 
existence  of  angina  scarlatinosa  would  be  highly  probable.  Follicular 
tons  llitis  not  infrequently  develops  in  persons  exposed  to  scarlatina 
who  have  previously  had  the  disease.  Thomas  says  that  all  such  cases 
should  be  regarded  with  suspicion,  but  we  would  hesitate  to  regard 
them  all  as  scarlet  fever.  The  symptoms  are  identical  with  follicular 
tonsillitis  occurring  from  other  sources.  We  have  known  persons 
unprotected  by  a  previous  attack  of  scarlet  fever  to  contract,  on  exposure 
to  the  disease,  what  appeared  to  be  an  ordinary  foil  cular  tonsillitis; 
although  no  eruption  was  discovered  in  these  patients,  they  have  at 
times  desquamated  on  the  feet  in  a  quite  characteristic  manner.  Patients 
with  sore  throats  of  this  nature  have  also  been  known  to  communicate 
scarlet  fever  to  others.  It  is  often  impossible  to  determ  ne  with  positive- 
ness  whether  or  not  cases  of  follicular  tonsillitis  resulting  from  exposure 
to  scarlet  fever  are  to  be  regarded  as  angina  scarlatinosa. 

Occasional  y  an  erythema  develops  in  the  course  of  an  ordinary 
follicular  tonsillitis.  This  eruption  is  often  partial  and  may  appear 
first  on  any  part  of  the  body.  The  exclusion  of  the  diagnosis  of  scarlatina 
is  only  possible  after  a  careful  study  of  all  of  the  symptoms,  general 
and  local,  and  attention  to  the  circumstances  of  exposure  and  epidemic 
influence. 


77//';  J'UOfJNOS/S  OF  SdAlffJ'/I'  FI'lVFIi  457 

THE  PROGNOSIS  OF  SCARLET  FEVER. 

The  most  important  factor  bearing  upon  the  prognosis  of  .scarlatina 
is  the  character  of  the  prevaiHng  epi(l(;mio.  Some  outbreaks  of  scarlet 
fever  are  of  extreme  mildness  and  others  are  frightfully  severe.  Syden- 
ham never  saw  a  severe  cas:^  of  the  disease  and,  tlierefore,  spoke  of  it 
"with  a  sort  of  coutcmj)t  wliich  ho  was  fjir  from  having  for  measles  or 
smallpox."  According  to  Trousseau,  his  illustrious  master,  liretonneau, 
had  not  seen  a  fatal  case  of  scarlet  fever  from  1799  to  1822;  he  was, 
therefore,  satisfied  that  "scarlet  fever  was  the  mildest  of  all  the  exan- 
themata." Later  experience  with  a  severe  form  of  the  disease  caused 
him  to  change  his  opinion  and  regard  the  malady  as  equally  mortal 
with  plague,  typhus,  and  cholera. 

The  character  of  scarlet-fever  epidemics,  as  regards  benignancy  or 
severity,  commonly  persists  for  a  period  of  years  before  a  change  in 
type  occurs.  Graves^  has  pointed  out  that  a  very  fatal  epidemic  ravaged 
Ireland  in  1800  to  1804.  Then  the  type  changed,  and  from  1804  to  18,31 
the  affection  was  so  wonderfully  mild  that  scarcely  any  deaths  occurred. 
In  1831,  however,  a  malignant  epidemic  broke  out  and  in  a  few  years 
spread  throughout  Ireland,  causing  tremendous  loss  of  life. 

It  is  evident,  therefore,  that  the  mortality  from  scarlatina  has  an 
extremely  wide  range.  It  may  fall  as  low  as  .3  per  cent.,  or  reach  the 
frightful  figure  of  40  per  cent.  Johannsen  states  that  in  an  epidemic 
in  certain  localities  in  Norway  the  death  rate  actually  reached  90  per 
cent.;  this  murderous  outbreak  is  absolutely  without  precedent. 

Hirsch  and  Thomas  hold  that  the  average  mortal  ty  of  scarlet  fever 
is  about  10  'per  cent.;  the  more  that  the  death  rate  exceeds  this  figure, 
the  greater  is  the  severity  of  the  epidemic.  When  the  death  rate  remains 
below  10  per  cent.,  the  epidemic  may  be  looked  upon  as  mild.  Thomas, 
in  enumerating  the  most  fatal  epidemics  of  scarlet  fever,  says  Hambursin 
in  Namur  lost  about  30  per  cent.;  Arrigoni  about  40  per  cent. ;  Salzmann, 
in  Esslinger,  from  1853  to  1857,  about  36  per  cent.;  at  Hornbach,  in  the 
Palatinate,  in  1868  to  1869,  34  per  cent. 

The  severity  of  scarlet  fever  has  been  diminishing  within  recent  years. 
Johannsen  says  that  among  84,580  reported  cases  in  Norway  there  were 
12,789  deaths,  a  mortality  of  14.17  per  cent.  He  regards  the  normal 
mortality  in  Norway  as  13  per  cent. 

Caiger^  states  that  during  the  past  twenty-three  years  81,350  cases 
of  scarlet  fever  have  been  treated  in  the  hospitals  of  the  ^Metropolitan 
Asylums  Board  of  London,  with  a  combined  mortality  of  8  per  cent. 
Since  1874  the  annual  percentage  has  progressivelv  fallen  from  12.2 
to  5.9. 

1  Quoted  by  Trousseau,  American  edition,  p.  137.  -  Loc.  cit.,  p.  128. 


458 


SCARLET  FEVER 


Year. 

Notifications. 

Deaths 

1890 

.    15,330 

876 

1891 

.     11,398 

589 

1892 

.     27,095 

1174 

1893 

.     36,901 

1596 

1894 

'      .        .     18,440 

962 

SCAELET-FEVER   MORTALITY   IN   LONDON   HOSPITALS.  (CaIGER.) 

General  Mortality.  Hospital  Mortality. 

5.71  7.86 

5.17  6.67 

4.33  '7.28 

4.32  6.11 

5.21  5.92 

The  higher  mortahty  in  the  hospitals  is  said  to  be  due  to  the  larger 
proportion  of  severe  cases  sent  in. 

The  death  rate  in  the  Municipal  Hospital  has  been  as  follows: 

Scarlet-fever  Mortality  in  the  Municipal  Hospital 
OF  Philadelphia. 


Year. 

Cases. 

Deaths. 

Percentage. 

Year. 

Cases. 

Deaths. 

Percent 

1891    . 

63 

2 

3.17 

1898    . 

380 

45 

11.84 

1892    . 

159 

14 

8:80 

1899    . 

604 

57 

9.43 

1893    . 

170 

32 

18.80 

1900    . 

646 

53 

8.20 

1894    . 

129 

11 

8.52 

1901    . 

.      1115 

108 

9.68 

1895    . 

163 

11 

6.73 

1902    . 

673 

56 

8.32 

1896     . 

253 

18 

7.11 

— 



1897     . 

858 

99 

10.37 

Total 

.      5213 

506 

9.72 

It  is  seen  from  these  figures  that  the  mortality  rate  is  somewhat  higher 
in  Philadelphia  than  in  London. 

The  factors  that  influence  the  prognosis  in  individual  cases  are  (1) 
the  age  of  the  patient,  (2)  the  virulency  of  the  infection,  and  (3)  the 
character  and  severity  of  the  complications. 

Age. — Age  affects  the  prognosis  in  a  most  striking  manner.  While 
the  general  mortality  of  scarlet  fever  is  from  10  to  12  per  cent.,  in  chil- 
dren under  five  years  of  age,  according  to  Holt,  it  is  between  20  and 
30  per  cent. 

In  our  own  cases  the  general  mortality  among  5213  cases  was  9.72 
per  cent.;  in  children  under  five  years  of  age  it  was  about  double  this 
figure — 18.6  per  cent. 

The  mort.ality  for  the  different  age  periods  of  patients  treated  in  the 
Municipal  Hospital  is  herewith  subjoined: 


Cases. 

Deaths. 

Percentage 

Under  one  year  of  age    . 

40 

13 

32.5 

One  to  five  years      .       .       .       . 

.    1670 

305 

18.32 

Five  to  ten  years      ... 

.     1766 

106 

6.0 

Ten  to  fifteen  years 

.      476 

19 

3.99 

Fifteen  to  twenty-five    . 

.      295 

18 

6.10 

Twenty-five  and  upward 

.      133 

7 

5.27 

The  above  table  shows  the  h'ghest  mortality  under  five  years  of  age, 
and  particularly  under  one  year.  In  the  first  year  of  life  about  one- 
third  of  our  patients  died. 

After  the  age  of  five  has  been  passed  the  mortality  diminishes  pro- 
gressively. The  death  rate,  in  our  own  experience,  reaches  its  minimum 
in  children  between  the  ages  of  ten  and  fifteen  years. 

Virulency  of  Infection. — Virulency  of  infect  on  is  indicated  by  great 
severity  of  the  invasive  symptoms.  The  prognosis  is  bad  when  the  tem- 
perature is  excessively  high — 106°  or  107°  F.;  when  convulsions,  stupor. 


TIII<:  TUf'JA  TMMNT  OF  SCA  IlLI'/r  FKVKR  45'J 

or  coma  develop;  when  the  eruption  is  irregular  or  partial  in  distribution, 
or  when  it  is  livid,  suppressed,  or  beniorrliaf^ic.  These  are  malignant 
cases  and  tlie  patient  is,  as  a,  rule,  overwli(;liried  early  iu  tlie  course  of 
the  disease. 

During  the  first  or  second  week  the  a[)pearance  of  severe  anginose  or 
septic  symptoms  renders  the  diagnosis  unfavorable. 

Patients  witli  a  sloughy  throat  with  tendency  to  gangrene,  great 
lymphatic  enlargement,  purulent  rhinitis,  and  otitis  are  apt  to  succumb 
to  the  poison  of  the  disease. 

Influence  of  Complications. — The  complications  which  are  most  apt 
to  cause  death  are  nephritis,  purulent  otitis,  meningitis,  endocarditis, 
pneumonia,  etc.  The  symptoms  of  evil  omen  in  nephritis  have  already 
been  referred  to.  It  shou'd  be  remembered  that  cases  of  scarlatina 
that  begin  in  the  most  benign  manner  may  develop  a  severe  nephritis 
with  its  attendant  dangers.  This  complication  comes  on  late,  during 
the  third  week,  at  a  period  when  the  patient  and  his  family  have  per- 
haps looked  forward  to  complete  convalescence. 

A  favorable  course  of  the  scarlet  fever  may  be  anticipated,  under 
ordinary  circumstances,  when  the  invasive  symptoms  are  but  moderately 
developed,  when  the  throat  is  but  mildly  involved,  when  the  eruption 
appears  at  the  proper  time,  gradually  reaches  its  maximum,  and  is 
uniformly  distributed;  when  the  fever  steadily  declines  with  the  fading 
of  the  exanthem,  and  when  complications  are  absent  or  of  short  duration. 

In  forecasting  the  result  of  an  attack  of  scarlet  fever,  it  is  wise  for  the 
physician  not  to  give  an  unqualifiedly  favorable  prognosis,  even  in  mild 
cases;  the  liability  to  serious  complications  in  this  disease  should  cause 
him  to  make  some  reservation  in  the  expression  of  an  opinion  as  to  the 
outcome  of  the  illness. 

THE  TREATMENT  OF  SCARLET  FEVER. 

In  the  discussion  of  the  treatment  of  scarlet  fever,  we  shall  take  up 
first  the  prophylactic  or  preventive  measures,  then  the  hygienic  care  of 
the  patient,  and,  finally,  the  direct  treatment  of  the  disease  and  its  various 
complications. 

Prophylaxis. — Scarlet  fever  is  an  endemic  disease  in  nearly  all  great 
centres  of  population,  and  the  health  authorities  of  these  common- 
wealths require  sanitary  regulations  for  the  control  and  prevention  of 
the  disease. 

As  a  prerequisite  to  the  prosecution  of  this  work  compulsory  notifica- 
tion is  essential.  The  health  authorities  must  know  when  and  where 
scarlet  fever  exists  in  order  to  be  able  to  check  its  farther  extension. 
It  is  the  custom  in  some  cities  to  placard  domiciles  in  which  scarlet 
fever  exists  in  order  to  warn  persons  who  might  be  otherwise  disposed 
to  enter  the  infected  houses.  While  this  plan  has  certain  distinct  advan- 
tages it  does  not  seem  to  have  found  favor  among  the  general  body  of 
physicians.  Boards  of  Health  should  have  the  power  of  thus  labeling 
infected  dwellings,  but  should  exercise  a  discriminating  judgment  in 


460  SCARLET  FEVER 

the  employment  thereof.  When  scarlet  fever  breaks  out  in  a  dwelling 
which  is  also  used  as  a  store  or  which  communicates  with  one,  the 
threatened  use  of  the  placard  will  often  determine  the  tenants  to  send 
the  patient  to  an  infectious  disease  hospital. 

In  the  event  of  refusal,  the  public  should  be  apprised  by  means  of  the 
placard  of  the  existence  in  the  building  of  the  disease  in  question. 

There  can  be  no  doubt  that  many  infectious  diseases  are  spread  through 
the  mingling  of  children  in  kindergartens  and  schools.  Scarlet  fever 
almost  invariably  decreases  during  the  summer  vacation  when  the 
schools  are  closed,  and  increases  again  when  the  sessions  begin.  Every 
effort  should  therefore  be  made  by  the  proper  authorities  to  prevent 
the  infection  from  being  transmitted  in  the  schools. 

The  procedure  in  vogue  in  most  large  cities  at  the  present  time  is  as 
follows:  The  head  of  the  school  is  notified  by  the  health  authorities 
that  one  of  the  pupils  is  sick  with  scarlet  fever,  and  that  he  is  not  to  be 
permitted  to  return,  save  after  certified  examination  by  a  medical 
nspector  or  some  other  duly  authorized  person.  Other  members  of 
the  same  household  that  are  in  attendance  at  school  should  likewise  be 
debarred  until  the  patient  has  been  sent  to  a  hospital  and  the  premises 
thoroughly  disinfected,  or  until  the  patient  has  completely  recovered 
from  his  illness  and  proper  domiciliary  disinfection  has  been  carried  out. 

A  child  who  develops  an  attack  of  scarlet  fever  should  be  debarred 
from  school  for  a  period  of  time  not  less  than  tivo  months.  Where  nasal 
or  aural  discharge  or  desquamation  persists  beyond  this  period  the 
enforced  vacation  must  be  still  further  extended.  While  such  a  rule 
often  works  hardship  it  will  be  found  to  best  conserve  the  public  health 
and  welfare. 

In  large  cities  it  is  an  excellent  plan  to  have  medical  inspectors  make 
frequent  examinations  of  the  pupils  in  the  public  schools,  with  a  view 
to  determining  the  existence  of  suspicious  sore  throats,  late  desqua- 
mation, etc.  Where  such  medical  service  cannot  be  commanded, 
teachers  should  be  instructed  in  the  symptoms  of  scarlet  fever,  so  that 
cases  presenting  suspicious  symptoms  might  be  immediately  sent  home. 
A  careful  and  intelligent  teacher  may  in  this  manner  often  discover  the 
disease  in  its  incipiency  and  send  the  patient  away  before  infection  is 
conveyed  to  others. 

If  these  precautions  be  carried  out  it  will  not  be  found  necessary 
except,  perhaps,  in  extensive  epidemics  to  close  public  schools.  The 
proper  ventilation  and  cleansing  of  schools,  rooms,  and  buildings  will 
greatly  lessen  the  danger  of  the  transmission  of  contagious  diseases. 

Isolation. — The  methods  of  isolation  which  are  employed  in  checking 
the  spread  of  infectious  diseases  in  general  can  be  utilized  with  much 
effectiveness  in  the  prevention  of  scarlet  fever.  This  is  true  (1)  because 
but  a  very  brief  period  elapses  before  the  appearance  of  the  characteristic 
eruption,  thus  making  possible  an  early  diagnosis,  and  (2)  because  the 
infection  is  not  apt  to  be  transmitted  during  the  first  few  days  of  the 
disease.  An  opportunity  is  thus  given  to  separate  the  patient  from  other 
members  of  the  family,  who  may  in  this  manner  be  protected.    In  this 


THF.  TUICATMFjNT  OF  HCAlifJiT  FEVER  461 

respect  scarlet  fever  differs  essentially  from  measles,  the  conta^ium  of 
which  is  given  off  at  a  very  early  date;  it  is  much  more  difficult  to  protect 
persons  who  have  been  exposed  to  a  case  of  measles  than  thf>se  who 
have  ])een  in  contact  with  scarlatina  during  the  (;;jrly  flays.  The  con- 
tagious principle  of  scarlatina  is  much  less  diffusihU'  than  that  of 
measles.  This  makes  it  possible  to  localize  the  infection  more  readily 
in  a  portion  of  a  house  or  a  hospital. 

In  households  in  wliich  an  ell'ective  isolation  can  be  carried  out,  the 
protection  of  other  members  of  the  family  can  be  accomplished  with 
reasonable  assurance.  It  must  be  recognized,  however,  under  these 
circumstances  that  eternal  vigilance  is  the  price  of  safety.  It  is  a  safer 
plan  to  remove  the  well  children  to  another  place.  The  liability  of 
their  contracting  the  disease  from  an  early  and  brief  exposure  and 
then  carrying  tlie  infection  with  them  is  not  very  great.  If  there  is 
fear  that  this  will  take  place  they  can  be  detained  at  home,  carefully 
separated  from  the  patient  for  a  week,  which  period  will  fully  cover 
the  stage  of  incubation. 

Where  effective  isolation  cannot  be  carried  out  at  home,  and  this  is 
the  case  in  the  large  majority  of  households  in  a  community,  the  patient 
should  be  sent  to  a  hospital,  the  whole  or  part  of  which  is  set  apart 
for  the  treatment  of  this  disease.  There  can  be  no  doubt  that  the 
treatment  of  scarlet  fever  in  special  hospitals  is  one  of  the  most  important 
means  of  preventing  the  spread  of  the  disease.  It  is  possible,  with 
hospital-treated  patients,  to  continue  the  isolation  until  every  vestige  of 
desquamation  has  disappeared,  and  until  discharges  from  the  nose  and 
ears  have  ceased.  This  may  in  some  cases  require  detention  in  the 
hospital  for  a  period  of  twelve  weeks  or  longer.  In  patients  treated  at 
home,  especially  among  the  poor,  who  are  not  so  apt  to  recognize  the 
responsibility  of  their  actions,  isolation  for  this  period  of  time  can 
seldom  be  enforced. 

A  very  large  number  of  cases  of  scarlet  fever  are  doubtless  contracted 
from  patients  who  are  prematurely  permitted  to  associate  with  others. 
This  naturally  brings  up  the  important  question:  i^oii'  long  are  scarlatina 
patients  to  be  isolated  and  quarantined  f 

This  query  is  by  no  means  easy  of  solution.  Indeed,  in  no  disease 
is  it  so  difficult  to  affirm  that  the  danger  of  infection  has  passed.  The 
rule  which  is  commonly  followed  is  to  continue  the  isolation  until 
desquamation  has  completely  ceased  and  the  patient  is  free  from  nasal 
and  aural  discharges.  In  the  average  case  this  will  cover  a  period  of 
six  or  seven  weeks.  In  some  cases  it  will  be  necessary  to  extend  the 
isolation  beyond  this  period  to  eight,  ten,  twelve,  or  even  fourteen  weeks. 
Despite  the  utmost  precaution  in  this  respect,  second  cases  will  at  times 
be  infected  at  a  late  date. 

All  large  scarlet-fever  -hospitals  receive  what  are  known  as  return 
cases.  A  certain  small  proportion,  about  2  per  cent,  of  the  dis- 
charged patients,  will  give  rise  to  cases  of  scarlet  fever  in  the  same 
household.  The  infection  may  be  conveyed  by  patients  who  have  been 
in  the  hospital  nine,  ten,  eleven  weeks  or  longer;  this  occurs  even  though 


462  SCARLET  FEVER 

desquamation  is  complete,  and  the  patient  antiseptically  bathed  and 
clad  in  perfectly  clean  garments.  The  infection  in  these  late  cases  is 
probably  derived  from  the  secretions  of  the  nose,  throat,  or  ears.  We 
have  already  made  mention  of  a  fatal  attack  of  scarlet  fever  contracted 
by  a  mother  from  a  child  who  was  discharged  from  the  Municipal 
Hospital  after  a  sojourn  of  nine  weeks.  This  woman  had  been  exposed 
to  her  child  at  an  early  stage  of  the  disease,  at  which  time  she  escaped 
infection.  We  have  observed  on  a  number  of  occasions  that  children 
who  are  exposed  to  the  infection  at  an  early  period  of  the  disease  may 
escape  only  to  contract  the  disease  from  a  patient  who  is  supposed  to 
be  free  of  contagion. 

The  Contagiousness  of  Desquamating  Epithelium. — The  view  has 
generally  been  maintained  that  the  infection  in  scarlet  fever  persists 
as  long  as  there  is  any  desquamation.  Within  recent  years  the  con- 
tagiousness of  the  scales  has  been  seriously  questioned. 

Millard,^  in  a  thoughtful  article,  challenges  the  view  that  scarlatinal 
desquamation  is  infectious.  The  author  obtained  the  opinions  of  a 
considerable  number  of  experts  whose  answers  he  has  formulated  as 
follows:  Sixteen  gentlemen  out  of  twenty-one  state  that  (1)  they  can 
adduce  no  evidence  that  desquamating  epithelium  is,  per  se,  a  source 
of  infection;  (2)  they  consider  that  too  much  importance  has  been  in 
the  past  attached  to  desquamation  as  a  source  of  infection;  (3)  their 
experience  does  not  support  the  popular  view  that  desquamation  after 
scarlet  fever  is  necessarily  an  indication  that  a  patient  is  still  infectious ; 
(4)  they  believe  that  a  patient  may  continue  to  desquamate  for  some 
time  after  he  has  ceased  to  be  infectious;  and  (5)  they  do  not  believe 
that  it  is  necessary,  in  order  to  prevent  the  spread  of  infection,  that 
patients  who  "otherwise  are  quite  ready  to  leave  the  hospital  should  be 
detained  until  every  visible  trace  of  desquamating  epithelium  has 
disappeared. 

In  conclusion  the  writer  briefly  sums  up  the  principal  arguments 
against  the  supposition  that  desquamation  is  infectious  as  follows: 
"1.  The  absence  of  evidence  supporting  it.  It  is  difficult  to  believe 
but  that  if  the  old  supposition  were  correct,  strong  evidence  of  it  would 
ere  this  have  been  forthcoming,  as  is  now  the  case  with  discharges  from 
the  nose  and  ears.  2.  The  fact  that  infectivity  begins  prior  to  the  onset 
of  desquamation  and  frequently  continues  long  after  desquamation  has 
ceased.  3.  The  fact  that  scarlet-fever  wards,  although  abounding  in 
desquamation  epithelium,  are  not  a  danger  to  neighboring  houses. 
4.  The  fact  that  the  proportion  of  'return  cases'  does  not  appear  to 
be  increased  among  patients  sent  out  from  hospital  still  desquamating. 
On  the  other  hand,  the  principal  argument  in  favor  of  the  view  that 
desquamation  is  infectious  is  the  fact  that  patients  still  desquamating, 
but  otherwise  apparently  free  from  infection,  have  frequently  been 
known  to  convey  the  disease  to  others.  The  whole  force  of  this  argu- 
ment disappears,  however,  when  we  consider  that  patients  apparently 

1  The  Supposed  Infectivity  of  the  Desquamation  in  Scarlet  Fever,  Lancet,  April  5, 1902. 


Tni<:  TfH<JATMf<JNT  OF  HCAItfJ'rr  FKVI'Hi  463 

quite  free  from  infection  and  \\\  wliorn  desquamation  has  entirely  ceased 
have  also  been  known  to  convey  the  disease;  moreover,  patients  still 
desquamatint^  have  fre(juently  mixed  freely  with  others  witliout  nntrnvard 
result." 

There  is  much  force  in  tlie  arguments  })resented  aljove.  It  is  quite 
possible  that  during  the  process  of  desquamation  the  infection  is  not 
in  tlie  scales,  but  in  the  pharyngeal,  nasal,  anrl  aural  secretions.  Not 
until  the  micro-organismal  cause  of  scarlet  fever  is  discovered  will  it 
be  possible  to  satisfactorily  solve  this  question.  In  the  mean  time  if 
we  err  it  should  be  upon  the  safe  side,  particularly  as  infection  apjjears 
to  reside  in  scarlatinal  convalescents  at  a  time  that  they  are  desqua- 
mating, and  often  for  a  long  period  subsequently. 

As  regards  second  desquamation,  most  observers  do  not  regard  it  as 
capable  of  transmitting  infection. 

There  are  some  apparent  cases  of  transmission  of  the  disease  during 
second  and  third  desquamation,  but  there  is  no  proof  that  the  scales 
conveyed  the  infection.  The  following  cases  were  mentioned  in  a 
committee  report  of  the  Clinical  Society  of  London:^ 

Case  24.==  On  April  1,  1878,  Master  P.  left  school  at  Wimbledon, 
on  the  fortieth  day  of  an  attack  of  scarlatina,  for  his  home  at  Brighton. 
Before  leaving,  desquamation  had  to  all  appearances  quite  terminated, 
the  feet  having  desquamated  twice.  Also,  he  had  repeated  carbolic  acid 
baths,  and  he  had  left  all  his  infected  clothes  behind.  After  reaching 
Brighton  his  face  and  feet  desquamated  again  and  four  days  after  his 
arrival  his  mother  fell  ill  with  scarlet  fever. 

Case  58.^  B.,  a  girl  aged  nineteen  years,  slept  one  night  with  a 
cousin  who  was  undergoing  a  second  desquamation  on  the  feet,  eight 
weeks  after  the  original  attack.  B.  developed  the  scarlet-fever  rash 
four  days  subsequently. 

Hygiene  of  the  Sick-apartments. — When  a  child  is  stricken  with 
scarlet  fever  it  should  be  immediately  isolated.  If  it  is  to  be  retained 
at  home  a  room  or  suite  of  rooms  in  the  uppermost  portion  of  the  house 
is  to  be  selected  as  the  sick-apartments.  Facilities  for  ventilation  should 
be  considered  whenever  a  choice  is  possible.  A  room  with  an  open 
fireplace  is  to  be  preferred,  although  such  a  convenience  is  seldom 
available.  An  excellent  plan  is  to  secure  the  ingress  of  fresh  air  through 
an  adjoining  room,  the  windows  of  which  may  be  kept  open  for  var^^ng 
periods  according  to  the  season.  This  room  should  constitute  the 
avenue  of  communication  with  other  portions  of  the  house. 

Carpets,  draperies,  ornaments,  and  all  dispensable  articles  of  furniture 
should  be  removed  from  the  room  before  occupancy  by  the  patient. 
The  spaces  about  doors  communicating  with  other  portions  of  the 
house  should  be  sealed  by  pasting  over  them  long  strips  of  wrapping 
paper.  Over  the  door  communicating  with  the  corridor  should  be 
suspended  a  sheet  which  is  kept  moistened  with  Labarraque's  fluid. 
a  5  per  cent,  carbolic  acid  solution,  or  1 :  1000  solution  of  bichloride 

1  Quoted  by  Millard.  =  Communicated  by  Dr.  Murchison  in  187S. 

3  Communicated  by  Dr.  Whitelegge. 


464  SCARLET  FEVER 

of  mercury.  InfectioUvS  particles  floating  in  the  atmosphere  will  adhere 
to  the  moistened  sheet. 

Great  care  should  be  exercised  to  keep  the  woodwork,  furniture, 
and  floors  scrupulously  clean;  this  is  best  accomplished  by  mopping 
with  cloths  saturated  with  one  of  the  above-mentioned  antiseptic 
solutions. 

No  one  save  the  person  selected  to  look  after  the  patient  should  be 
permitted  in  the  sick-room.  If  the  mother  acts  as  nurse  she  should 
devote  her  time  exclusively  to  the  patient  and  should  not  come  in 
contact  with  any  other  members  of  the  family.  The  nurse  should  not 
leave  the  sick-apartments  except  after  complete  change  of  clothing, 
bath,  and  shampooing  of  the  hair  with  an  antiseptic  solution.  Such 
garments  should  be  worn  by  the  nurse  or  mother  as  can  be  readily 
boiled  or  otherwise  disinfected.  The  hair  should  be  protected  by  a  cap 
in  order  that  it  harbor  as  little  infection  as  possible. 

Recognizing  that  the  scarlet-fever  contagium  is  readily  carried  in 
clothing  and  upon  various  articles,  it  becomes  the  duty  of  the  physician 
to  take  such  precautions  as  to  reduce  the  liability  of  transmitting  the 
disease  to  a  minimum.  He  should,  before  entering  the  sick-room,  don 
a  gown  which  extends  from  the  neck  to  the  feet.  A  cap  should  be  worn 
to  cover  the  hair,  and  it  is  a  good  plan,  during  the  desquamative  stage, 
to  protect  the  shoes  with  rubbers.  Upon  leaving  the  patient  the  physician 
should  wash  the  hands,  face,  beard,  and  exposed  portions  of  the  hair 
with  an  antiseptic  soap. 

Before  visiting  other  children  he  should  endeavor  to  get  a  thorough 
airing  out-doors.  It  is  best  for  physicians  who  happen  to  have  obstetrical 
and  scarlet-fever  patients  at  the  same  time  to  relinquish  the  care  of  the 
one  or  the  other. 

That  the  above  precautions  are  not  superfluous  is  evidenced  by  the 
not  infrequent  carrying  of  scarlatina  by  physicians.  Murchison  investi- 
gated this  subject  and  was  informed  by  many  physicians  that  they  had 
conveyed  the  disease  through  their  infected  clothing. 

Adult  members  of  a  household  in  which  scarlet  fever  exists  should 
safeguard  the  interests  of  others  by  avoiding  contact  with  the  world. 
The  best  guide  under  these  conditions  is  the  golden  rule. 

All  articles  coming  in  contact  with  the  patient  should  be  subjected 
to  disinfection.  In  the  room  adjoining  the  sick-apartment  should  be 
kept  a  5  per  cent,  solution  of  carbolic  acid  which  should  be  used  to 
cleanse  utensils,  body  and  bed  linen,  etc.  The  linen  should  be  steeped 
in  the  antiseptic  solution  for  an  hour  or  two,  then  wrung  out,  placed  in 
a  receptacle  outside  the  room,  and  finally  cleansed  with  scalding  water 
and  laundered. 

It  is  preferable  when  possible  to  retain  the  dishes  and  eating  utensils 
within  the  sick-apartments.  When  they  must  be  sent  to  other  parts 
of  the  house  to  be  cleansed  they  should  first  be  immersed  for  half  an 
hour  in  boiling  water. 

Discharges  from  the  ears,  nose,  and  throat  should  be  received  upon 
pieces  of  muslin  or  cheese-cloth,  which  should  be  burned  or  disinfected. 


Tiii<:  ruf'JATMi':NT  of  scaulht  fever.  405 

Where  a  sputum  ciij)  is  used  il,  slioiild  confjiin  a  solution  of  ciuholir; 
acid  or  cliloridc;  of  lime;  tlio  siuiu^  is  Iimk;  of  urinals  and  bed-pans. 

Disinfection.-  -  After  (lie  (ermination  of  \\\(\  illness  tlie  patient  ^liould 
be  given  an  antisepti(;  hath  of  1  :  1(),()0()  hicliloride  of  mereury.  The 
head  should  be  thoroughly  washed  with  antiseptic  soap  and  clean  or 
new  clothing  put  on.  It  is  a  wise  precaution  to  prevent  association  of 
the  patient  with  other  children  for  several  weeks  after  the  quarantine 
has  been  raised.  The  disinfection  of  the  sick  apartments  shou  d  }>e 
carried  out  with  tlioroughness.  If  perfunctory  fumigation  is  relied  upon 
to  destroy  all  infection,  unfortunate  consequences  may  follow.  The 
infection  of  scarlet  fever  has  a  remarkable  tenacity  and  may  remain 
resident  in  articles  for  months  or  years.  Numerous  instances  of  this 
are  referred  to  in  the  chapter  on  Ktiology. 

All  articles  of  little  or  no  value  in  the  sick-room  should  be  burned. 
This  is  particularly  true  of  those  things  with  which  the  patient  has 
been  in  contact,  such  as  body-linen,  books  and  toys. 

The  apartments  should  be  thoroughly  fumigated  or  sprayed,  prefer- 
ably with  formaldehyde  solution;  as  a  matter  of  extra  precaution  this 
should  be  used  in  greater  amounts  than  that  ordinarily  prescribed 
for  the  given  air  space.     (See  chapter  on  Disinfection.) 

The  floors,  woodwork,  and  furniture  should  be  vigorously  scrubbed 
with  a  carbolic  acid  solution  of  about  1  part  to  40.  The  walls,  if 
painted,  should  be  washed  with  the  same  solution.  If  the  walls  are 
covered  with  paper  it  is  wisest  to  have  them  scraped  and  repapered. 

Blankets,  mattresses,  upholstered  furniture,  clothing,  etc.,  should  be 
disinfected  by  superheated  steam  under  pressure.  Many  large  cities 
are  now  equipped  with  dis  nfecting  plants  to  wh'ch  all  such  articles 
may  be  sent.  Where  such  is  not  the  case  the  blankets  and  bed- linen 
after  being  fumigated  had  better  be  boiled  and  the  mattress  destroyed 
by  burning. 

It  is  a  wise  plan,  whenever  possible,  to  allow  the  sick-apartments  to 
remain  unoccupied  and  exposed  for  some  days  or  weeks  to  the  purif\'ing 
influence  of  sunlight  and  fresh  air. 

The  above  precautions  may  be  troublesome  and  expensive,  but  it  is 
by  careful  attention  to  these  matters  that  attacks  of  scarlet  fever  are 
often  prevented  and  human  life  and  faculties  thus  preserved. 

In  the  event  of  death  from  scarlet  fever  the  body  should  be  enveloped 
in  a  sheet  wet  with  a  1 :  1000  solution  of  bichloride  of  mercury.  It 
should  be  placed  in  a  hermetically  sealed  casket  and  buried  at  as  early 
a  date  as  possible.    The  interment  should,  of  course,  be  private. 

Care  of  Patient.  Diet.^ — During  the  early  days  of  scarlatina,  when 
the  fever  is  high,  milk  constitutes  the  best  and  usually  the  most  accept- 
able diet.  Cool  milk  is  soothing  to  the  throat  and  assuages  the  intense 
thirst  which  is  present  in  severe  cases.  ]Most  writers  insist  upon  an 
exclusive  milk  diet  throughout  the  entire  febrile  period,  and  many 
counsel  its  continuance  during  the  early  convalescent  stage.  When  the 
patient  is  willing  to  take  a  sufficient  quantity  of  milk  to  maintain  his 
body  weight  there  can  be  no  objection  to  an  exclusive  milk  diet;  but 

30 


466  SCARLET  FEVER 

some  children  and  many  youths  and  adults  object  to  the  monotony  of 
an  exclusive  milk  diet.  We  have  had  an  excellent  opportunity  of  judging 
of  the  effect  of  diet  in  scarlet  fever.  For  many  years  the  scarlatina 
patients  in  the  Municipal  Hospital  received  an  exclusive  milk  diet 
during  the  febrile  period.  For  the  past  eight  months,  during  which 
time  over  500  patients  were  treated,  the  patients  have  had  a  more 
liberal  dietary.  They  were  encouraged  to  drink  plenty  of  milk,  but 
were  permitted  as  soon  as  they  cared  to,  to  have  bread  and  butter  with 
their  meals  and  a  simple  pudding  and  stewed  fruit  once  a  day.  We 
found  that  patients  desired  nothing  but  the  milk  while  the  temperature 
was  high,  but  that  when  it  became  lower  they  were  eager  to  obtain 
bread  and  butter  in  addition.  Our  patients  appeared  to  progress  just 
as  well  under  the  enlarged  dietary.  Urinary  examinations  were  made 
every  other  day  and  the  results  compared  with  those  under  the  exclusive 
milk  diet. 

Albuminuria  was  not  more  frequent  in  the  former  than  in  the  latter 
and  the  renal  complications  altogether  were  of  a  mild  character.  We 
present  these  facts  for  what  they  are  worth.  It  is  a  hardship  for  some 
patients  to  be  denied  solid  food  for  weeks,  and  they  may  as  a  result 
receive  an  insufficient  amount  of  nourishment.  We  have  never  seen 
the  above  diet  do  any  harm. 

Caiger^  allows  patients,  during  the  febrile  stage,  milk  with  eggs  beaten 
up,  broths,  and  calves-foot  jelly.  When  the  temperature  falls  he  permits 
eggs,  custard,  light  puddings,  and  bread  and  butter.  Ripe  and  succulent 
fruit  is  given  at  any  time  throughout  the  illness.  Caiger  states  that 
there  is  no  risk,  as  has  been  alleged,  of  inducing  a  nephritis  by  permitting 
these  articles  of  food  to  be  taken. 

Our  present  practice  is  to  use  an  exclusive  milk  diet  in  infants  and 
very  young  children  and  in  cases  of  nephritis,  but  to  allow  older  children 
and  adults  a  little  more  latitude.  The  latter  frequently  request  light 
solid  foods,  and  we  believe  that  when  there  is  an  appetite  for  such 
articles  they  do  no  harm. 

Confinement  to  bed  should  be  enforced  during  the  febrile  period,  and, 
during  cold  and  inclement  weather,  in  severe  cases  for  a  week  or 
more  after  the  subsidence  of  the  fever.  Young  and  restless  children 
whose  actions  cannot  be  well  controlled  had  better  be  kept  in  bed 
from  three  to  four  weeks,  or  until  the  liability  of  nephritis  has  passed. 

While  it  is  generally  believed  that  "catching  cold"  has  been  greatly 
exaggerated  as  a  factor  in  nephritis,  Griffith  states  that  chilling  of  the 
surface  certainly  acts  as  a  powerful  accessory  cause  in  the  production 
of  complications. 

The  detention  of  the  patient  in  his  bed  or  room  will  be  influenced 
by  the  age  of  the  individual,  the  season,  and  other  factors  which  the 
discretion  of  the  physician  must  solve. 

In  view  of  the  liability  to  kidney  complications,  it  is  necessary  to 
keep  the  skin,  which  is  an  important  eliminatory  organ,  in  a  functionally 

1  Loc.  cit.,  p.  170. 


77//';  rU/'JATMI'JNT  OF  HCAULI'/I'  Fl-Vhlli  467 

active  state.  All  (clinicians  are  agreed  as  to  the  a(]visal)ility  of  cinployiiig 
sponge  baths;  tepid  water  is  preferably  used  and  should  be;  apph(;d 
twice  daily.  In  addition  to  promoting  gentle  diaphoresis  these  baths 
subserve  the  ends  of  comfort  and  cleanliness. 

To  lessen  the  tension  of  the  skin  and  allay  it(;hing  the  inunction  of 
some  unguentous  substance  is  desirable.  We  have  for  years  employed 
cacao-butter  for  this  purpose  and  have  found  it  cleanly  and  agreeable 
alike  to  nurses  and  patients.  When  much  itching  is  present  a  1  per  cent, 
menthol  or  2  per  cent,  carbolic  ointment  may  be  used. 

Inunctions  of  salves  containing  oil  of  eucalyptus,  ichthyol,  certain 
silver  salts,  and  many  other  substances  have  from  time  to  time  been 
lauded  as  possessing  special  therapeutic  virtues. 

Medical  Treatment.^ — It  must  be  frankly  admitted  that  we  possess 
no  medicament  capable  of  directly  influencing  or  abridging  the  course 
of  scarlet  fever.  Our  therapeutic  efforts  must  be  directed  toward 
combating  excessive  development  of  the  symptoms  and  toward  prevent- 
ing and  modifying  complications.  The  treatment  is,  therefore,  purely 
symptomatic  in  character. 

In  mild  cases  of  scarlet  fever  special  medication  is  often  unnecessary, 
the  disease  progressing  to  a  favorable  termination  under  the  influence 
of  proper  hygienic  care  and  nursing. 

During  the  febrile  stage  it  is  customary  to  administer  a  febrifuge 
mixture.  We  have  been  in  the  habit  of  using  a  combination  of  the 
liquor  ammonite  acetatis  and  sweet  spirit  of  nitre,  sw^eetened  with  a 
little  syrup. 

Vomiting,  when  present,  may  be  controlled  by  abstinence  from  food 
and  the  administration  of  fractional  doses  of  calomel.  Constipation 
may  be  corrected  by  the  latter  drug,  or  one  of  the  mild  vegetable 
laxatives. 

It  is  advisable  to  use  some  mild  antiseptic  in  the  throat,  not  only  to 
relieve  the  congestion  and  soreness,  but  to  lessen  secondary  infection 
and  the  habihty  of  extension  of  inflammation  to  the  middle  ear. 

Fever. — There  are  many  cases  in  which  attention  must  be  directed 
to  the  control  of  high  temperature  and  the  accompanying  nervous 
phenomena.  Scar.et  fever  is  frequently  characterized  by  a  very  high 
initial  pyrexia,  which  tends  in  a  few  days  to  defervesce.  When  the  fever 
is  above  103°  F.,  and  particularly  when  there  are  severe  nervous  symptoms, 
such  as  headache,  delirium,  stupor,  or  convulsions,  antipyretic  measures 
should  be  employed.  In  the  reduction  of  temperature  preponderant 
reliance  is  now  placed  upon  hydrotherapy.  Different  clinicians  have 
individual  preferences  as  to  the  mode  of  appl^-ing  water ;  the  methods  m 
vogue  are  tepid  sponge  baths,  cold  sponge  baths,  wet  or  cold  packs,  and 
warm,  graduated,  or  cold  tub  baths.  Ice-bags  and  Leiter's  coils  are 
also  employed. 

The  routine  treatment  of  scarlet  fever  with  cold  tub  baths,  as  in  the 
case  of  typhoid  fever,  has  not  met  with  general  favor.  They  may  be 
employed  in  cases  accompanied  by  great  hyperpyrexia,  provided  there 
is  no  pronounced  cardiac  depression.     Cold  baths  are  not  borne  well 


468  SCARLET  FEVER   ' 

by  infants  or  very  young  children,  and  should  not  be  used  in  such 
cases. 

In  cases  of  average  severity  with  high  fever,  sponging  with  cold  water, 
with  or  without  alcohol,  will  usually  suffice  to  keep  the  temperature 
within  proper  bounds.  If  this  does  not  control  the  fever  and  nervous 
symptoms,  resort  may  be  had  to  the  cold  pack,  which  has  a  more  pro- 
nounced antipyretic  influence.  In  milder  cases  it  may  be  all  sufficient 
to  keep  an  ice-bag  or  cold  coils  applied  to  the  head. 

Warm  tub  baths  of  about  the  temperature  of  95°  F.  are  recommended 
by  many  physicians.  These  will  frequently  reduce  a  high  temperature, 
and  are  more  acceptable  to  the  patient  and  the  members  of  his  family 
than  cold  baths;  or  the  graduated  bath  may  be  used,  the  temperature 
gradually  being  lowered  until  the  desired  reduction  in  the  fever  is 
accomplished. 

The  old  superstition  about  baths  being  dangerous  and  causing 
patients  to  "catch  cold"  has  been  dissipated,  and  a  complete  unanimity 
of  sentiment  now  exists  among  physicians  as  to  the  desirability  of  using 
baths  of  one  kind  or  another  in  scarlet  fever. 

Medicinal  antipyretics  are  used  to  a  very  limited  extent  nowadays. 
The  general  feeling  is  that  they  are  dangerous  in  large  doses  and  in- 
effective in  small  amounts.  Phenacetin  in  small  doses  (2  to  3  grains) 
may  be  given  as  an  adjunct  to  hydrotherapy  in  bad  cases,  or  to  relieve 
headache  and  nervous  symptoms  in  milder  cases,  Antipyrin  and 
acetanilid  are  not  in  favor,  as  they  are  apt  to  cause  too  much  cardiac 
depression. 

Throat. — Where  the  throat  shows  but  slight  involvement  mild  anti- 
septic fluids  may  be  employed,  either  in  the  form  of  a  spray  or  a  gargle. 
For  this  purpose  a  weak  Dobell  solution  or  a  solution  of  boric  acid 
or  chlorate  of  potash  may  be  employed.  Very  young  children  cannot 
use  a  gargle,  and  often  vigorously  object  to  efforts  at  swabbing  or  spray- 
ing the  throat.  Where  the  physical  resistance  is  so  pronounced  as  to 
exhaust  the  child  the  procedure  is  of  doubtful  advantage  and  had 
better  be  discontinued.  In  the  anginose  variety  of  the  disease  it  is 
equally  important  to  cleanse  the  nares  and  throat  and  to  avoid  an 
exhausting  resistance.  A  firm  and  skilful  nurse  is  of  great  assistance 
under  such  circumstances. 

When  the  throat  is  severely  involved  and  a  streptococcus  pseudo- 
membrane  is  present,  systematic  and  vigorous  treatment  is  indicated. 
Not  only  does  the  pharyngeal  inflammation  tend  to  spread  to  the  nares 
and  middle  ear,  but  a  general  infection  is  apt  to  result  from  strepto- 
coccic absorption. 

In  these  cases  the  throat  should  be  frequently  sprayed  with  peroxide 
of  hydrogen,  plain  or  diluted,  according  to  the  age  of  the  patient  and 
the  degree  of  inflammation  present  in  the  fauces. 

In  septic  cases  with  ulceration  of  some  of  the  soft  tissues,  Caiger^ 
speaks  in  terms  of  high  praise  of  a  strongly  acid  solution  of  chlorate  of 

1  Loc.  cit.,  p.  171. 


77//';  THKATM/'JNT  OF  SdAh'LI'/J'  h'EVI'lll  4G9 

potash -containing  a  large  amonnf  of  Free  cliloiinc.'  Tlio  lliro;it  .-md 
nose  are  irrigated  witli  tliis  fluid  by  means  of  a  soft-rubber  syringe 
with  a  vulcanite  nozzle,  the  head  being  held  over  a  bnsiri  wifli  tlie 
mouth  kept  open. 

Caiger  says:  "No  amount  of  gargling,  spraying,  or  swabbing  fan 
compare  with  it  (this  method)  in  ])oint  of  cflicaey." 

Forchheimer  speaks  highly  of  direct  applications  to  flic  throat  by 
means  of  a  swab  saturated  with  I^oeffler's  iron-toluol  solution.  This 
shonld  be  applied  once  or  twice  a  day  and  held  in  contact  with  the 
diseased  parts  for  a  little  while  to  secure  the  best  results.  In  cases  of 
extensive  streptococcic  exudate  in  the  throat  this  writer  counsels  the 
use  of  antistreptococcus  serum,  which,  he  believes,  will  occasionally 
improve  the  local  symptoms  in  a  remarkable  manner. 

Purulent  Rhinitis. — Purident  rhinitis  in  scarlet  fever  is  apt  to  accom- 
pany severe  throat  involvement.  The  extension  of  the  suppurative 
inflammation  to  the  nasal  mucous  membrane  increases  the  1  ability  to 
general  sepsis  and  augments  the  gravity  of  the  disease.  A  sanious,  sero- 
purulent  discharge  issues  from  the  nostrils  in  great  quantities.  The 
efforts  of  the  nurse  must  be  directed  toward  systematic  and  frequent 
cleansing  of  the  nasal  cavities.  But  this  must  be  done  with  great  care 
and  gentleness.  The  forcible  projection  of  liquids  into  the  nose  will 
do  harm,  as  will,  hkewise,  the  use  of  strong  and  irritating  antiseptics. 
It  has  been  our  custom  to  have  the  nose  gently  irrigated  with  a  warm 
saline  solution;  this  is  done  with  a  small  glass  piston-syringe  with  a 
blunt  end.  In  obstinate  cases  we  have  recently  employed  a  10  per  cent, 
solution  of  argyrol,  one  of  the  newer  silver  compounds.  This  remedy 
has  lessened  the  profuse  discharge  and  has  led  to  a  healthier  condition 
of  the  parts. 

Patients  with  gangrenous  destruction  of  the  soft  palate  or  tonsils  do 
not,  as  a  rule,  recover.  Apart  from  the  stronger  remedies  referred  to 
in  the  treatment  of  membranous  angina,  one  may,  in  this  condition, 
employ  a  warm  solution  of  permanganate  of  potash,  1 :  2000.  In 
circumscribed  gangrenous  patches  we  have  frequently  applied  the 
tincture  of  iodine  with  good  results. 

Noma. — Noma  is  fortunately  an  uncommon  complication  of  scarlet 
fever.  When  the  condition  is  still  in  its  incipiency  the  pultaceous  deposit 
upon  the  mucous  surface  should  be  scraped  away  with  a  curette  and  the 
base  thoroughlv  cauterized  with  fuming  nitric  acid.  This  had  better 
be  done  under  the  use  of  ether,  which  can  be  given  in  just  sufficient 
quantity  to  benumb  the  patient's  sensibilities.  If  the  cutaneous  surface 
becomes  attacked,  free  excision  will  be  found  to  be  a  not  too  radical 
procedure. 

Glands. — The  glands  at  the  angle  of  the  jaw  commonly  attain  the 
greatest  size  and  most  frequently  undergo  suppuration.     Glandular 

1  According  to  Caiger  the  solution  is  prepared  by  pouring  strong  hydrochloric  acid  upon  powdered 
chlorate  of  potash  in  a  large,  stoppered  bottle.  The  proportions  advised  are  5  minims  of  strong 
acid  to  9  grains  of  the  salt,  with  suflScieut  water  to  make  an  ounce.  The  solution  is  of  a  greenish 
cplor,  and  has  a  strong  chlorine  odor. 


470  SCARLET  FEVER 

abscess  may  be  expected  in  nearly  all  cases  of  anginose  scarlatina.  In 
the  beginning  an  ice-bag  should  be  applied  about  the  neck.  A  special 
bag  manufactured  for  this  purpose  buttons  around  the  neck  and  keeps 
the  ice  in  close  apposition  with  the  affected  glands.  A  piece  of  flannel 
should  be  interposed  between  the  bag  and  the  skin.  A  dried  pig  s 
bladder  filled  with  small  pieces  of  ice  will  answer  the  purpose  when  an 
ice-bag  is  not  'available. 

If,  despite  the  application  of  cold,  the  gland  increases  in  size  and 
suppuration  becomes  inevitable,  heat  should  be  substituted.  Flaxseed 
poultices,  rendered  antiseptic  by  having  incorporated  in  them  a  1 :  4000 
solution  of  corrosive  sublimate,  hasten  the  suppurative  process.  Upon 
the  first  suspicion  of  pus  formation  an  incision  into  the  gland  should 
be  made  and  free  drainage  established.  It  is  better  to  lance  prematur-ely 
than  to  delay  too  long,  for  inflammation  may  spread  to  the  periglandular 
tissues.  When  cellular  infiltration  takes  place  free  incisions  should  be 
made,  even  though  no  pus  focus  can  be  demonstrated,  for  by  this  means 
the  deep -burrowing  pus  which  forms  later  may  be  anticipated  and  the 
most  fatal  of  complications — Ludwig's  angina — may  be  prevented. 

The  Ears. — Inasmuch  as  otitis  media  is  an  extremely  common  com- 
plication of  scarlet  fever,  it  should  be  guarded  against  as  much  as 
possible  and  the  condition  promptly  met  when  it  develops.  The  prophy- 
lactic treatment  relates  to  those  measures  which  are  designed  to  keep 
the  nasopharynx  clean  and  free  of  infective  secretions.  While  this 
object  is  a  laudable  one,  no  treatment  will,  in  bad  cases,  prevent  the 
development  of  otitis  media.  Indeed,  it  may  be  stated  that  the  liability 
to  ear  complications  is  directly  proportionate  to  the  severity  of  involve- 
ment of  the  throat  and  nose. 

Pain  in  the  ear  is  best  relieved  by  the  application  of  heat;  this  may 
be  accomplished  by  syringing  gently  with  water  as  hot  as  can  be  borne, 
or,  better  still,  by  the  use  of  external  dry  heat.  The  hot-water  bag  or 
hot  salt  or  bran  bag  may  be  placed  against  the  ear.  Dench  suggests 
heating  a  little  salt  in  the  tip  of  a  kid-glove  finger  and  thrusting  the 
same  into  the  ear.  The  instillation  of  a  few  drops  of  a  warm  4  per  cent, 
solution  of  cocaine  is  advised  by  some  writers. 

When  the  pain  continues  despite  these  measures,  suppuration  is 
probable.  If  upon  inspection  of  the  tympanic  membrane  bulging  is 
seen,  an  incision  should  be  made  to  evacuate  the  pus.  It  should  be 
remembered,  however,  that  in  very  young  children,  in  whom  otitis 
is  commonest,  the  small  size  of  the  canal  and  the  restlessness  of  the 
patient  make  aural  inspection  and  paracentesis  extremely  difficult  and 
unsatisfactory.  Furthermore,  spontaneous  rupture  is  the  rule  in  these 
cases,  and  may  be  the  first  evidence  of  involvement  of  the  ears. 

After  drainage  is  established  it  is  necessary  to  keep  the  external 
auditory  meatus  clean  and  free  of  pus.  Various  liquids  are  advised, 
such  as  1:5000  solution  of  bichloride  of  mercury,  1  in  4  solution  of 
peroxide  of  hydrogen,  saturated  solution  of  boric  acid,  etc.  We  have 
found  boiled  water  containing  a  little  carbolic  soapsuds  very  useful. 
All  solutions  should  be  used  warm  and  injected  gently  with  a  soft-rubber 


Till']  tiii<:atmi<:nt  of  s(jaiuj<:t  Fi'!V/<jfi  471 

bulb  ear  syringe.  The  meatus  should  not  be  plugged  with  fottfHi. 
Sudden  ri.se  of  teni})eratur(!  indicates  a  stoppage  of  flr;iinag(?  or  cxlcn.sion 
of  iiiflaminidion  to  adjacent  ,stni('turcs.  Any  swelling  in  tlie  mastoid 
region  should  be  promj)tly  and  fre(;ly  incisctd  juid  f)rop(;r  drainage 
maintained.  There  should  be  no  hesitancy  about  ('nt<;ring  the  mastoid 
antrum  if  the  bone  exhibits  evidence  of  disease.  In  all  such  cases  the 
services  of  an  aural  surgeon  should  be  called  into  rcc|uisition. 

Joints. — Scarlatinal  synovitis  or  arthritis  fscai'latinal  rheumatism) 
calls  for  both  local  and  constitutional  treatinent.  Physiciuns  are  not 
all  in  accord  as  to  the  value  of  the  salicylates  in  inflamed  joints  in  this 
disease,  although  many  testify  to  their  efficiency.  Where  the  joint 
involvement  is  pronounced  they  should  be  given  a  trial;  if  no  improve- 
ment is  noted,  or  if  the  stomach  is  deranged  or  the  heart  depressed, 
their  adm  nistration  had  better  be  interrupted.  The  inflamed  joints 
should  be  painted  v^ith  tincture  of  iodine,  surrounded  by  cotton-wool 
and  bandaged  with  a  flannel  bandage.  Increase  of  fever,  chills  and 
sweats,  with  aggravation  of  the  local  symptoms,  indicate  the  presence 
of  pus  in  the  joints.  The  joints  should  be  incised,  through  and  through 
drainage  established,  and  the  cavity  washed  out  with  antiseptic  solutions. 
When  there  is  doubt  as  to  the  presence  of  pus,  the  aspirating  needle  may 
be  used  and  a  small  quantity  of  fluid  drawn  out.  When  streptococci 
are  present  in  the  synovial  fluid  the  use  of  antistreptococcic  serum  is 
advised.  During  convalescence  from  articular  complications  care  should 
be  taken  to  preserve  the  mobility  of  the  joint  by  gentle  massage  and 
passive  movements.  In  all  cases  of  joint  involvement  the  heart  should 
be  carefully  watched,  for  cardiac  complications  are  much  more  common 
under  these  circumstances. 

Kidneys. — Nephritis  is  one  of  the  most  common  and  most  serious 
complications  of  scarlet  fever.  It  not  infrequently  occurs  in  mild  cases, 
at  a  time  when  the  patient  is  considered  almost  well.  It  is  a  good  plan 
to  keep  patients  in  bed  for  at  least  three  weeks,  as  it  is  during  the  third 
week  of  the  disease  that  nephritis  is  most  frequently  discovered.  The 
urine  should  be  examined  each  day  for  both  albumen  and  tube  casts. 
Ordinarily  the  chemical  and  microscopic  examinations  of  the  urine 
will  enable  one  to  determine  the  onset  of  a  nephritis.  In  rare  cases 
sudden  and  alarming  symptoms  may  develop  without  the  previous 
occurrence  of  albuminuria.  It  is  of  importance,  where  nephritis  is 
suspected,  to  have  the  quantity  of  urine  excreted  in  each  twenty-four 
hours  carefully  measured.  Pallor,  puffing  of  the  face,  and  elevation 
of  temperature  are  among  the  early  clinical  evidences  of  oncoming 
nephritis. 

When  albumin  is  found  the  patient  should  be  kept  in  bed  and  the 
temperature  of  the  room  kept  w^arm  and  equable.  The  diet  should  be 
restricted  to  milk,  which,  with  water,  the  patient  should  be  encouraged 
to  drink  in  large  quantities.  The  bowels  should  be  kept  freely  open 
and  the  action  of  the  skin  encouraged  by  daily  warm  baths.  Under  this 
simple  regimen  the  vast  majority  of  cases  will  make  a  good  recover}'. 

If  the  urine  is  reduced  in  quantity  and  the  s^nnptoms  do  not  improve, 


472  SCARLET  FEVER 

a  more  active  treatment  should  be  pursued.  We  have  found  the  use  of 
a  diuretic  mixture  containing  infusion  of  digitalis  and  acetate  of  potash 
of  especial  value.  Calomel  may  be  given  in  sufficient  dosage — about 
■^  gr.  three  times  a  day— to  produce  two  or  three  movements  a  day; 
this  drug  has  the  advantage  of  increasing  renal  secretion  at  the 
same  time.  It  is  an  excellent  plan  to  place  over  the  kidneys  a  warm 
poultice  composed  of  1  part  of  ground  mustard  to  15  parts  of  flaxseed 
meal.     This  should  be  renewed  every  two  or  three  hours. 

Vomiting,  flushed  face,  and  a  high-tension  pulse  indicate  the  use 
of  nitroglycerin.  This  drug  may  be  administered  to  children  in  the 
dosage  of  -g-^Q-  to  ^-o^o"  gr.  every  few  hours  until  the  physiological  efi^ect 
is  produced. 

The  development  of  ursemic  symptoms  such  as  twitchings,  delirium, 
or  stupor  necessitates  vigorous  treatment.  Free  but  not  excessive 
catharsis  should  be  produced  by  calomel  or  salines.  The  patient  should 
be  given  a  hot  pack  or  a  hot  vapor  or  hot-air  bath.  In  using  the  pack 
the  patient  is  enveloped  in  a  blanket  which  is  wrung  out  of  water  of 
100°  F.  temperature;  this  is  surrounded  by  a  dry  blanket  and  this  in  turn 
by  a  rubber  mackintosh.  After  free  sweating  is  induced,  the  blankets 
can  be  removed  and  the  patient  rubbed  dry.  The  hot  pack  may  be 
used  twice  a  day. 

In  the  hot-air  bath  the  patient  is  enveloped  in  blankets  between 
the  folds  of  which  are  placed  hot  bricks  or  bottles.  Where  these 
measures  do  not  sufiice,  pilocarpine  may  be  given  hypodermically. 
The  dose  varies  from  -^^  gr.  to  -j-^  gr.  according  to  age;  for  a  child  five 
years  of  age  -^  gr.  may  be  given.  Owing  to  the  frequent  depressing 
effect  of  this  drug  in  children  its  administration  had  better  be  preceded 
or  accompanied  by  alcoholic  stimulation.  It  is  advised  that  pilocarpine 
be  withheld  in  cases  in  which  there  is  profuse  bronchial  secretion,  to 
avoid  a  possible  pulmonary  oedema. 

If  convulsions  develop  the  hydrate  of  chloral  should  be  given  either 
by  the  mouth  or  bowel.  A  hypodermic  injection  of  morphine  is  often 
of  great  value.  If  the  convulsive  seizures  are  persistent  they  should  be 
controlled  by  inhalations  of  chloroform.  In  desperate  cases  it  is  well 
to  perform  venesection  and  follow  the  abstraction  of  blood  by  the  intra- 
venous injection  of  salt  solution. 

Alarming  symptoms  may  result  from  cedema  of  the  lungs  or  from 
effusion  of  serum  into  the  pleural  or  pericardial  sac.  These  conditions 
must  be  borne  in  mind  and  carefully  wa  ched  for. 

A  certain  degree  of  anaemia  is  apt  to  follow  severe  cases  of  nephritis. 
For  this  condition  iron  in  the  form  of  Basham's  mixture  will  be  found 
to  serve  a  useful  purpose. 

After  a  severe  nephritis  great  care  should  be  exercised  concerning 
the  patient's  diet  and  hygiene.  The  urine  should  be  carefully  examined 
at  frequent  intervals.  If  albuminuria  persists  and  becomes  subacute, 
the  child  should,  if  possible,  be  sent  to  a  warm  climate,  where  he  should 
remain  during  the  winter  months.  Every  precaution  should  be  taken 
to  protect  the  patient  against  exposure. 


77//';  TUf'JATM/'JNT  OF  SCARfJCT  FFVh'U.  473 

The  Heart. — In  severe  cases  of  scarlet  fever  it  is  frequently  necessary 
to  support  a  flafr^infj^  heart.  When  the  first  sound  is  weak  or  the  pulse 
is  rapid,  small,  or  irregular,  cjirdiac  stimulation  is  imperative.  The 
majority  of  cases  of  scarlot  fev(;r  will  not  r(!f|uirc  the  us(;  of  alcoljol, 
but  one  should  not  hesitate  to  use  a  good  brandy  or  whiskey  in  full 
doses  when  the  heart  gives  evidence  of  failing  power.  Digitalis  will 
serve  a  useful  purpose  when  the  stomach  is  tolerant.  When  digitalis 
is  not  well  l)orne,  strophanthus  maybe  su})stituted.  Stryc-hnine  in  .^ ,',  r» 
to  y,V()  gr.  doses  will  often  i)e  found  valuable.  When  the  ])crij)h('ral 
circulation  is  feeble,  resort  may  be  had  to  hypodermics  of  nitroglycerin, 
g^-  Tfio"  to  TTiyj  every  few  hours.  The  subcutaneous  injection  of  camphor 
dissolved  in  ether  or  almond  oil  may  tide  over  a  threatened  collapse. 

Endocarditis  and  pericarditis  develop  most  commonly  in  association 
with  scarlatinal  rheumatism.  Involvement  of  the  joints  should  cause 
one  to  be  vigilant  concerning  cardiac  complications.  Upon  the  first 
suspicion  of  valvular  trouble  an  ice-bag  should  be  placed  over  the  heart 
and  the  salicylates  should  be  cautiously  administered  or  continued  if 
they  were  previously  being  used.  The  patient  should  })e  kept  at  perfect 
rest  in  a  horizontal  position.  We  have  seen  sudden  dilatation  of  the 
heart  result  from  the  patient  sitting  up.  If  pericarditis  with  effusion 
is  present,  it  may  become  necessary  to  attempt  an  evacuation  of  the 
pericardial  fluid. 

Gastrointestinal  Tract. — The  early  vomiting  is  seldom  persistent; 
when  treatment  is  necessary,  abstinence  from  food,  the  swallowing  of 
pellets  of  ice,  and  the  administration  of  fractional  doses  of  calomel  will 
control  the  emesis.  Early  diarrhoea  need  not  be  interfered  with  if  it  is 
mild.  If  it  is  severe  it  may  be  controlled  by  the  use  of  bismuth,  vegetable 
astringents,  and,  if  necessary,  opium.  The  same  treatment  should  be 
applied  to  profuse  bowel  movements  developing  late  in  the  disease. 
If  the  inflammation  is  in  the  large  intestines,  irrigation  of  the  colon 
with  a  warm  saline  solution  or  mild  astringents  and  antiseptics  wil'  be 
found  useful. 

Purpura. — Hemorrhages  into  the  skin  and  from  the  nose,  mouth, 
kidneys,  bowels,  etc.,  may  develop  during  the  second  or  third  week  of 
scarlet  fever.  The  patients  become  extremely  anaemic  and  may  die 
from  the  loss  of  blood.  In  a  case  under  our  care  of  purpura  -with  epis- 
taxis  and  bleeding  from  the  mouth  and  kidneys,  the  patient  gradually 
going  from  bad  to  worse,  rapid  improvement  followed  the  administra- 
tion of  turpentine.  Five  minims  of  turpentine  were  given  in  an  emul- 
sion of  acacia  and  elixir  of  orange,  every  two  or  three  hours.  The 
hemorrhage  stopped  in  less  than  a  day  and  the  patient  made  a  good 
recovery,  the  previously  existing  nephritis  not  being  aggravated  by  the 
turpentine.  This  drug  is  highly  recommended  in  purpura  by  Crocker, 
of  London.  Ferruginous  preparations  are  indicated  in  the  anaemia  that 
follows  these  attacks 

Malignant  cases  of  scarlet  fever,  characterized  by  a  mottled  and 
cyanotic  surface,  cold  extremities,  with  or  without  high  internal  fever 
(as  indicated  by  the  rectal  temperature),  require  vigorous  stimu-ation. 


474  SCARLET  FEVER 

A  hot  mustard  bath  should  be  given  to  increase  the  peripheral  circulation 
and  lessen  internal  congestion.  Trousseau  counselled  the  use  of  ammonia 
and  musk  in  this  condition.  Jacobi  advises  the  use  of  ammonia,  musk, 
and  camphor,  and  considers  these  drugs  superior  to  alcohol.  He  also 
recommends  in  these  cases,  when  the  temperature  is  low,  the  use  of 
morphine  in  doses  of  -^-q  to  -j^  of  a  grain,  repeated  according  to  effect. 

In  malignant  attacks  and  also  when  uraemia  is  threatened  it  is  advis- 
able to  employ  subcutaneous  or  intravenous  injections  of  a  decinormal 
saline  solution  (yq-  per  cent,  solution  of  sodium  chloride  in  sterilized 
water) ;  200  to  500  c.c.  may  be  injected  in  a  child.  In  uraemia  the 
injection  may  be  preceded  by  venesection. 

Serotherapy. — On  account  of  the  great  frequency  with  which  strepto- 
cocci are  found  in  the  throat  and  in  various  organs  which  are  the  seat 
of  complications  in  scarlet  fever,  attenapts  have  been  made  to  make 
an  antistreptococcus  serum  to  combat  the  complications  and  even  the 
disease  itself. 

Marmorek  prepared  an  antistreptococcus  serum  which  has  been 
used  to  a  considerable  extent  in  this  disease.  The  results  are  inconclusive 
and  not  particularly  encouraging.  Josias,  in  1896,  used  the  Marmorek 
serum  at  the  Trousseau  Hospital  with  disappointing  results.  The  serum 
cases  appeared  to  do  no  better  than  a  control  series  of  cases  receiving 
no  serum.  Baginsky  employed  this  same  serum  without  benefit.  Forch- 
heimer  used  the  serum  as  a  routine  practice  in  a  limited  number  of 
cases  of  scarlet  fever.  The  serum  did  not  affect  the  course  of  the  disease 
in  any  way,  but  occasionally  the  local  symptoms  of  streptococcus  angina 
were  improved  most  remarkably. 

More  recently  Moser^  has  employed  a  new  antistreptococcus  serum. 
He  states  that  among  669  cases  of  scarlet  fever  in  the  St.  Anna  Hospital 
in  Vienna,  81  received  the  serum.  Among  cases  receiving  injections  on 
the  first  and  second  days  of  the  disease  there  was  no  mortality.  Later 
injections  gave  a  gradually  rising  death  rate:  third  day,  14.29  per 
cent.;  fourth  day,  23.88  per  cent.;  fifth  day,  40  per  cent.  Moser  states 
that  the  clinical  symptoms  improve  promptly  after  the  serum  is  intro- 
duced. The  different  pus  processes  and  nephritis  are  lessened  in 
frequency,  but  not  altogether  prevented.  The  mortality  among  400 
cases  of  scarlet  fever  in  the  St.  Anna  Kinderspital  in  1901  was  8.9  per 
cent.,  as  against  an  average  mortality  for  scarlatina  of  13.09  per  cent, 
in  other  hospitals  in  Vienna  in  which  serum  was  not  used. 

Baginsky  has  attacked  Moser's  conclusions  as  to  the  value  of  his 
serum.  Baginsky  has  treated  50  cases  of  scarlet  fever  with  a  serum 
made  by  Aronson  from  a  throat  streptococcus,  and  from  one  obtained 
from  bone-marrow  from  a  scarlatinal  subject.  Of  these  58  cases,  3  died, 
giving  a  mortality  of  4.2  per  cent.  Including  moribund  cases  and  several 
cases  that  died  from  other  causes,  there  were  62  cases  with  7  deaths, 
or  11.3  per  cent,  mortality.  As  compared  with  this  series  there  were 
63  not  treated  by  serum,  of  whom  9  died,  a  mortality  of  17.3  per  cent. 

1  Berliner  klin.  Wochenschrift,  October  20, 1902,  p.  995. 


TlfE  TREATMENT  OF  SCARLET  FEVER  475 

Ba^insky  is  inclined  to  look  favor;i,hly  upon  tfie  .serum  treatment, 
although  the  results  thus  far  have  not  been  very  striking. 

Use  of  Blood  Serum  of  Convalescents. — Roger'  reports  the  case 
of  a  boy,  aged  fifteen  years,  suffering  from  an  extremely  severe  scarlet 
fever,  who  entered  the  hospital  on  the  second  day  of  the  disease.  A 
hypodermoclysis  of  400  grams  of  saline  solution  was  administered. 
The  patient  was  semicomatose,  pulse  120,  respirations  08,  and  temper- 
ature 40.2°  C.  Urine  almost  suppressed.  The  prognosis  was  almost 
hopeless.  A  convalescent  was  bled  and  100  grams  of  blood  recovered. 
This  was  rapidly  defibrinated  and  80  c.c.  injected  beneath  the  skin  of 
the  patient's  abdomen,  after  venesection  had  been  performed  uy)on  him. 
Five  hours  later  the  patient  was  sleeping  quietly  and  breathing  more 
easily,  but  still  in  a  dangerous  condition,  with  suppression  of  urine. 
The  patient  was  given  a  bath  to  reduce  the  temperature  and  saline 
solution  was  again  injected.  The  following  day  the  patient  was  com- 
pletely transformed;  consciousness  returned;  the  patient  spoke  freely, 
felt  well,  and  asked  for  food.  The  patient  made  a  good  recovery.  Roger 
remarks  that  he  never  saw  such  a  rapid  recovery  after  so  grave  a  case. 

Hiiber  and  BlumenthaP  also  used  human  blood  serum  in  scarlet  fever. 
They  obtained  the  serum  by  venesection  of  convalescents  from  four 
to  twenty-one  days  after  the  subsidence  of  fever.  The  blood  was 
immediately  mixed  with  an  equal  amount  of  a  sterile  saline  solution 
and  1  per  cent,  of  chloroform  added.  It  was  then  vigorously  shaken 
and  allowed  to  stand  for  twenty-four  hours.  It  was  then  strained 
through  linen  and  filtered  through  a  Berkefeld-Nordmeyer  apparatus. 
Thirteen  cases  of  scarlet  fever  were  injected  with  this  serum,  20  c.c.  to 
40  c.c.  being  employed.  In  only  3  cases  was  a  positive  beneficial  result 
noted;  in  8  cases  the  result  was  not  very  pronounced. 

More  evidence  is  needed  before  any  conclusions  can  be  drawn  as  to 
the  value  of  this  method  of  treatment. 

Baginsky  has  used  Crede's  ointment  of  colloidal  silver  in  the  treatment 
of  a  number  of  grave  cases  of  scarlet  fever.  The  cases  were  septic  ones 
of  unusual  severity,  and  but  3  out  of  the  13  recovered.  The  results  were 
disappointing  and  serve  to  negative  the  claims  made  for  this  method 
of  treatment. 

1  Presse  m6d.,  1896,  iv.  p.  245 ;  also  Les  maladies  iufect.,  p.  1372. 

2  Berliner  klinische  Wochenschrift,  1897,  No.  31. 


CHAPTEE    IX. 

MEASLES. 

Definition. — Measles  is  an  acute,  contagious,  febrile  disorder,  char- 
acterized by  catarrhal  symptoms  affecting  the  upper  respiratory  tract, 
and  an  eruption  of  dusky-red,  slightly  elevated  macules.  The  disease 
commoly  occurs  in  epidemics  and  attacks  for  the  most  part  children; 
one  attack  confers  immunity  in  the  vast  majority  of  cases. 

Synonyms  and  Derivation. — Rubeola,  morhilli;  French,  la  rougeole; 
German,  masern,  flecken;  Italian,  morhilli,  rosalia;  Spanish,  serampion. 

The  word  measles  is  probably  derived  from  an  old  English  word, 
maseles.  Hirsch  calls  attention  to  the  resemblance  to  the  German 
masern  and  the  Sanskrit  masura,  meaning  spots.  The  term  morhilli  is 
derived  from  the  Italian  morhillo,  which  signifies  the  little  disease.  This 
diminutive  was  doubtless  employed  to  distinguish  measles  from  small- 
pox, the  plague,  il  morho,  probably  referring  to  the  latter  affection. 

History. — It  is  impossible  to  state  with  any  degree  of  positiveness  the 
date  of  origin  of  measles.  Some  writers  have  attempted  to  prove  that 
measles  existed  in  the  days  of  Hippocrates,  but  such  an  assertion  does 
not  appear  to  be  warranted  by  the  writings  of  the  Greek  and  early 
Roman  physicians.  The  references  in  the  medical  literature  of  this 
period  are  so  vague  as  to  offer  a  very  inadequate  basis  for  the  belief 
that  they  refer  to  so  clear-cut  a  disease  as  measles.  Most  writers  concur 
in  the  opinion  that  both  measles  and  smallpox  definitely  made  their 
appearance  about  the  tenth  century.  They  appeared  to  have  had  their 
origin  in  the  countries  bordering  on  the  Red  Sea,  and  from  this  region 
to  have  spread  westwardly  throughout  Europe.  The  first  clear  mention 
of  measles  is  attributed  to  that  master  Arabian  physician,  Rhazes,  who 
lived  about  a.d.  910.  His  distinguished  successors,  Hali  Abbas  and 
Avicenna,  described  measles  under  its  Arabic  designation,  Hasha,  or 
al  hashet.  The  term  rubeola  was  later  brought  into  use  by  the  Latin 
translators  of  the  Arabian  writings.  Morbilli  was  very  loosely  applied 
to  many  exanthematous  conditions. 

The  Arabian  physicians  regarded  measles  as  a  variety  of  smallpox. 
Willan^  attempted  to  identify  in  the  writings  of  Hippocrates  and  other 
early  writers  references  to  smallpox  and  measles,  and  quotes  the  descrip- 
tion of  Serapion,  an  Arabian  physician.^ 

Avicenna  looked  upon  measles  as  a  bilious  smallpox.  Sennertus  in 
1640  proposed  as  a  subject  of  enquiry  the  reason  why  the  disease  in 
some  constitutions  appeared  as  smallpox  and  in  others  as  measles. 

Diemerbroeck,  in  a  posthumous  work  published  in  1687,  says:  "The 
matter  by  which  the  measles  is  generated  is  not  so  thick  as  in  the  case 

1  Robert  Willan's  Miscellaneous  Works,  edited  by  Ashby  Smitb,  London,  1821,  p,  46. 

2  Tbeorice,  lib.  viii.  cap.  14, 


MEAHLKH  477 

of  smallpox.  It  is  drier  and  somewhat  choleric;."  He  rcgarderl  rnea.sles 
and  smallpox  as  diflerent  varieties  of  the  same  disease. 

SydenliJiin,  altliouf^h  a  eonteniporary  of  the  Dutch  physician  just 
quoted,  was  a  mu(;h  closer  observer.  lie  carefully  studied  the  symj>toms 
of  measles  during  the  epidemic  of  1070-74,  and  his  description  of  the 
disease  (barring  a  few  terms,  for  instance  the  use  of  the  word  pustule) 
com})ares  not  unfavorably  with  j)resent-day  writings:  "The  measles 
generally  attack  children.  On  the  first  day  th(;y  have  chills  and  shivers, 
and  are  hot  and  cold  in  turns.  On  the  second  day  they  have  the  fever 
in  full — disquietude,  thirst,  want  of  appetite,  a  white  (but  not  a  dry) 
tongue,  slight  cough,  heaviness  of  the  head  and  eyes,  and  somnolence. 
The  nose  and  eyes  run  continually,  and  this  is  the  surest  sign  of  measles. 
To  this  may  be  added  sneezing,  a  swelling  of  the  eyelids  a  little  before 
the  eruption,  vomiting,  and  diarrhoea  with  green  stools.  These  appear 
more  especially  during  teething  time.  The  symptoms  increase  until  the 
fourth  day.  Then,  or  sometimes  on  the  fifth,  there  appear  on  the  face 
and  forehead  small  red  spots,  very  like  the  bites  of  fleas.  These  increase 
in  number  and  cluster  together,  so  as  to  mark  the  face  with  large  red 
blotches.  They  are  formed  by  small  papulae,  so  slightly  elevated  above 
the  skin  that  their  prominence  can  hardly  be  detected  by  the  eye,  but 
can  just  be  felt  by  passing  the  fingers  lightly  along  the  skin. 

"The  spots  take  hold  of  the  face  first,  from  which  they  spread  to 
the  chest  and  belly,  and  afterward  to  the  legs  and  ankles.  On  these 
parts  may  be  seen  broad,  red  maculae,  on  but  not  above  the  level  of 
the  skin.  In  measles  the  eruption  does  not  so  thoroughly  allay  the 
other  symptoms  as  in  smallpox.  There  is,  however,  no  vomiting  after 
its  appearance;  nevertheless  there  is  slight  cough  instead,  which,  with 
the  fever  and  the  difficulty  of  breathing,  increases.  There  is  also  a 
running  from  the  eyes,  somnolence,  and  want  of  appetite.  On  the  sixth 
day,  or  thereabouts,  the  forehead  and  face  begin  to  grow  rough  as  the 
pustules  (?)  die  off  and  as  the  skin  breaks.  Over  the  rest  of  the  body 
the  blotches  are  both  very  broad  and  very  red.  About  the  eighth  day 
they  disappear  from  the  face  and  scarcely  show  on  the  rest  of  the  body. 
On  the  ninth  there  are  none  anywhere.  On  the  face,  however,  and 
on  the  extremities— sometimes  over  the  trunk — they  peel  off  in  thin, 
mealy,  squamulae,  at  which  time  the  fever,  the  difficulty  of  breathing, 
and  the  cough  are  aggravated." 

To  Sydenham  belongs  the  distinction  of  trenchantly  separating  small- 
pox and  measles.  But  scarlatina  and  measles  were  still  confounded. 
Twenty  years  later  jNIorton  regarded  measles  and  scarlet  fever  as  due 
to  the  same  miasm;  he  asserted  that  they  bore  the  same  relation  to  each 
other  as  discrete  and  confluent  smallpox.  ]Many  writers  of  this  period 
spoke  of  scarlatina  under  the  designation  of  morhUli  confJuenfes. 

Reports  of  epidemics  which  were  undoubtedly  mealses  were,  according 
to  Fuchs,  published  bv  Forestus  (1563),  Lange  (1565),  Ballonius 
(1574-75),  and  Schenk  (1600). 

As  far  as  any  accurate  knowledge  is  concerned,  measles  is  a  disease  of 
comparatively  modern  origin. 


**^' 


478  MEASLES 

THE  ETIOLOGY  OF  MEASLES. 

Measles  may  be  regarded  as  the  inost  contagious  of  the  various 
exanthematous  affections.  When  it  breaks  out  in  a  household  or  an 
institution  it  is  almost  impossible  to  prevent  its  spread,  so  diffusible  is 
the  contagious  principle  which  causes  it.  This  fact  and  the  universal 
susceptibility  to  the  disease  make  ^measles  the  commonest  malad^i.to 
which  human  flesh  is  heir.  But  few  persons  go  through  life  without 
at  some  time  or  other  passing  through  an  attack  of  measles.  When  it  is 
escaped  during  childhood  it  is  extremely  apt  to  be  contracted  during 
dult  life;  in  this  respect  it  differs  markedly  from  scarlatina,  against 
which  most  adults  acquire  an  immunity. 

Whether  or  not  measles  can  be  successfully  inoculated  still  remains 
in  doubt,  despite  the  very  considerable  experimentation  and  literature 
on  the  subject. 

In  1758,  Francis  Home,  of  Edinburgh,  attempted  the  inoculation  of 
measles  at  the  suggestion  of  Monro.  He  saturated  bits  of  muslin  with 
blood  obtained  by  incising  through  the  measle  lesions.  These  were  laid 
open  upon  the  excoriated  arms  of  healthy  persons.  In  this  manner 
he  claims  to  have  inoculated  twelve  children,  in  most  cases  with  success, 
although  the  disease  appeared  in  a  mild  form.  Pieces  of  muslin  moist- 
ened with  the  nasal  secretion  which  were  placed  in  the  nostrils  of  healthy 
children  failed  to  produce  the  disease.  Theussink,^  who  attended 
Home's  clinics  and  saw  these  experiments,  expresses  doubt  as  to  Home's 
interpretation  of  the  results.  At  Theussink's  suggestion,  his  friend 
Themmen  later  repeated  these  inoculations  in  1816  with  negative  results. 

In  1822  Speranza  successfully  inoculated  measles,  and  claims  to  have 
had  the  disease  himself  in  this  manner.  In  1854,  an  Italian  physician, 
Bufalini,  reported  successful  results  both  of  his  own  and  his  countrymen, 
Locatelli,  Rossi,  and  Figueri;  Horst  and  Percival  are  likewise  credited 
with  positive  inoculations. 

In  1842  Katona^  performed  1122  inoculations  in  twenty-six  townships 
of  the  Borsoder  Comitates;  93  per  cent,  of  these  were  successful,  the 
attacks  being  of  a  mild  character.  An  admixture  of  blood  and  the  con- 
tents of  miliary  vesicles  taken  at  the  height  of  the  rash  was  rubbed  into 
excoriations  made  after  the  manner  of  vaccination.  At  the  end  of  seven 
days  fever  and  the  usual  prodromal  symptoms  developed;  the  eruption 
appeared  two  or  three  days  later,  about  the  ninth  or  tenth  day  after 
the  inoculation. 

Mayr  successfully  inoculated  measles  in  1848  and  in  1852.  He  placed 
freshly  secreted  nasal  mucus  from  a  case  of  measles  in  the  nostrils  of 
two  children  living  at  a  distance  from  one  another.  At  the  end  of  eight 
and  nine  days,  respectively,  catarrhal  symptoms  developed,  followed  in 
a  few  days  by  fever  and  the  eruption.    In  an  article  on  measles^  published 

1  Abhandlung  iiberdie  Maseru,  translated  from  the  Dutch  by  Dr.  Doden,  of  Giittingen. 

2  Nachricht  von  einer  im  Grossen  erfolgreich  vorgenommenen  Impfung  der  Masern  wiihrend  einer 
epidemischen  Verbreitung  derselben,  Osterreich.  med.  Wochenschrift,  1842,  No.  29,  pp.  697-98. 

3  Mayr's  article  on  Measles  in  Hebra's  Diseases  of  the  Skin,  1866. 


77//';  i<:ti()IJ)(!y  of  m/'JAsiJ'JS  470 

in  1866,  Mayr  remarks:  " Inoculations  with  l)Iood  made  by  myself  in 
1848  and  1852  afforded  iiepjative  results."  The  use  of  d(;s(juainatin^ 
skin  also  failed  to  traiisnn't  the  disease,  as  had  previously  oeeurred  in 
the  ex])eriineiits  of  Ahix.'uider  Monro.  The  negative  n.-sults  in  the 
transmission  of  measles  by  the  inoculation  of  blood,  in  the  hands  of 
Thenimen,  Albers,  Mayr,  and  Thomson,  should  cause  us  to  accept  the 
alleged  successful  results  with  some  reservation.  Only  after  there  has 
been  confirmation  by  ])erfectly  relial)le  and  careful  observers,  under 
conditions  that  preclude  the  possibility  of  the  natural  transmission  of 
the  disease,  should  measles  be  regarded  as  an  inoculable  affection. 

The  usual  mode  of  contagion  in  measles  is  by  direct  exposure  to  a 
person  suffering  from  the  disease.  The  contagium  of  measles  differs 
from  that  of  scarlet  fever  in  two  respects — it  is  more  diffusible  anrl  it  is 
less  tenacious;  the  infection  does  not  tend  to  any  marked  degree  to  cling 
to  objects  or  apartments,  and  transmission  of  the  disease  by  fomites  is, 
therefore,  distinctly  unusual. 

Richard^  claims  that  the  contagium  of  measles  cannot  be  carried  by 
fomites  nor  by  a  protected  person.  Bard^  states  that  the  contagium  of 
measles  does  not  remain  viable  in  a  locality  from  which  patients  have 

removed.     Comby^  says  that  the  germ  of  measles  has  but  little  vitality  . 

outside  of  the  body,  and  that  every  germ  that  emanates  from  a  measles 
patient  is  dead  at  the  end  of  a  few  hours. 

While  we  are  not  prepared  to  dogmatically  state  that  measles  cannot 
be  carried  by  infected  objects  or  third  persons,  our  experience  is  in 
accord  with  that  of  most  writers  that  such  occurrences  must  be  ver\' 
rare.  Von  Kerchensteiner  calls  attention  to  the  observation  that 
physicians'  children  do  not  as  a  class  contract  measles  earlier  in  life 
than  other  children.  Considering  the  frequent  neglect  of  precautionary 
measures,  this  would  not  be  the  case  if  the  disease  were  readily  trans- 
missible through  infected  garments. 

Official  reports  of  the  extensive  epidemic  of  measles  in  the  Faroe    / 
Islands  in  1846  (at  which  time  over  6000  persons  were  attacked)  gave 
no  instances  of  transmission  of  the  disease  by  infected  articles  or  by 
third  persons,  and  this  point  was  carefully  investigated  by  the  physicians 
who  studied  this  epidemic. 

Theussink  states  that  he  knew  of  a  case  where  the  infection  was 
conveyed  by  a  letter  sent  through  the  post,  and  also  an  instance  where 
it  was  attributed  to  an  engraving  sent  by  mail.  The  negative  evidence 
of  intermediate  infection  is  so  abundant  that  such  cases  must  be  sub- 
stantiated beyond  the  perad venture  of  a  doubt  before  they  can  be 
unreservedly  accepted. 

When  measles  breaks  out  in  a  family  circle  it  attacks  all  of  the  sus- 
ceptible members  thereof.  Kindergartens  and  schools  offer  fertile 
opportunity  for  the  dissemination  of  diseases.  Consequently  measles, 
as  well   as    the  other   contagious   diseases  of   children,  is   much  more 

1  Therapeutic  Gazette,  July  16,  18SS. 

-  Revue  d'hygioue  et  de  Police  Sanitaire,  May  20, 1S91. 

3  Trait6  des  mal.  de  I'enfauce. 


480  MEASLES 

common  during  the  periods  of  the  year  that  these  institutions  are  in 
session. 

SusceptibiHty  to  measles  is  practically  universal.  All  mankind, 
almost  without  exception,  will  take  the  disease  when  exposed  to  it. 
The  temporary  insusceptibility  exhibited  by  very  young  infants  will 
be  referred  to  later. 

One  of  the  most  remarkable  and  instructive  epidemics  of  measles 
in  history  is  that  which  visited  the  Faroe  Islands_ija,-I846.^  These 
islands  had  been  free  from  measles  since  ITSl^  a  period  oFsixty-five 
years.  The  disease  was  introduced  by  a  Danish  cabinetmaker  who  had 
become  infected  in  Copenhagen.  On  his  arrival  at  Thorshavn,  the  chief 
port  of  the  islands,  he  communicated  the  disease  to  two  friends.  These 
persons  gave  rise  to  an  epidemic  which  in  a  short  space  of  time  attacked 
over  6000  subjects  out  of  a  population  of  7782.  Persons  of  all  ages  were 
stricken  and  almost  every  household  was  converted  into  a  hospital. 
The  old  inhabitants  who  had  passed  through  an  attack  as  children  in 
1781  alone  escaped.  Not  one  old  person  who  was  exposed  to  the 
infection,  and  was  unprotected  by  previous  attack,  failed  to  take  the 
disease. 

That  certain  individuals  may  exhibit  a  temporary  immunity  against 
measles  is  recognized  by  most  writers.  THomas  says :^**T~oB'served, 
during  an  epidemic  among  about  130  cases,  5  children,  2  of  whom  were 
boys  of  two  and  three  years,  evince  an  immunity  during  this  epidemic, 
while  2,  boys  of  eight  and  twelve  years,  and  a  girl  of  nine  years  had 
evinced  it  as  well  during  previous  ones." 

Hoff  makes  mention  of  3  .men,  acting  as  nurses  in  the  epidemic  of 
1846  in  the  Faroe  Islands,  who  remained  exempt,  but  who  contracted 
the  diseas  '  when  it  recurred  in  the  islands  in  1875. 

Spiess^  states  that  a  number  of  children,  varying  in  age  from  four  to 
seventeen  years,  after  having  been  previously  exposed  to  measles  without 
contracting  it,  fell  ill  in  2  cases  after  seven  weeks,  in  1  after  two 
months,  in  4  after  two  and  a  half  months,  and  in  1  after  five  months. 

Moore^  reports  the  case  of  a  boy  who,  passing  through  two  epidemics 
of  measles  with  impunity,  fell  ill  during  a  third  and  gave  the  disease  to 
a  younger  brother,  who  at  the  time  of  the  first  invasion  was  not  born, 
but  who  had  successfully  resisted  the  second  one. 

It  is  difficult  to  explain  this  temporarily  absent  susceptibility,  but  it 
is  quite  analogous  to  that  observed  in  suckling  infants. 

The  presence  of  an  acute  disease  is  apt  to  temporarily  diminish 
susceptibility  to  measles,  or,  when  the  infection  is  received,  to  postpone 
its  outbreak  until  convalescence  from  the  first  disease.  This  is  true  of 
most  of  the  exanthematous  affections.  The  susceptibility  to  measles 
may  even  be  temporarily  abolished  during  the  existence  of  another  acute 
malady.    An  instance  of  this  has  recently  attracted  our  attention. 

1  This  remarkable  epidemic  was  carefully  studied  and  reported  by  Panum,  who  visited  seventeen 
of  the  twenty  islands  of  the  group  during  a  period  of  four  months.  A  later  epidemic  in  1875  was 
assiduously  investigated  by  E.  M.  HoflF;  SundhedscoUegiets  Aarsberetning  for  1876. 

*  Quoted  by  Thomas,  loc.  cit.  s  Quoted  by  Thomas,  loc.  cit. 


77//!,'  KTIOLOCIV  OF  M/'JASLFS  481 

A  boy,  aged  five  years,  was  believed  to  be  su fieri ug  from  smallpox  and 
was  sent  into  the  wards  of  the  Municipal  IFospitaJ  devoted  to  this  dis- 
ease. On  making  our  rounds  we  discovered  tliat  the  boy  harl  measles 
at  the  height  of  Uw.  eruj)tive  stage  aufl  not  small[)Ox;  he  was  immedi- 
ately transferred  to  other  quarters.  He  had  been  in  the  ward  about 
fifteen  hours;  in  this  same  ward  were  about  fifteen  children,  from  a  few 
months  to  twelve  years  of  age,  suffering  from  smallpox  in  its  various 
stages.  Some  of  these  children  later  succumbed  to  small})Ox;  but  not 
one  contracted  measles. 

Age. — Measles  most  commonly  attacks  indivichials  l^etween  the  ages 
of  one  and  ten  years.  Jllliis  age .  incideucc  is.  determined  by  several 
factors  ail  ahnosi  universal  vulnerability  to  the  disease,  a  diminished, 
"siiscepliltiliiy  (hii-ing  the  (irst  year  of  life,  and.  the  imiiiunity  conferred- 
by  one  altack.  There  can  be  no  doubt  that  infants  under  one  year  of 
age  and  particularly  those  under  six  months  will  commonly  escape 
measles  when  exposed  to  the  disease.  This  is  ef|ually  true  of  rubella, 
and,  in  a  measure,  true  also  of  scarlet  fever.  This  immunity  is  not 
absolute,  but  only  relative.  There  are  numerous  records  of  infants  of 
tender  age  who  have  contracted  measles,  but  under  six  rnontlis  tliey 
are  very  apt  to  resist  the  infection  altogether. 

Pfeilsticker^  reports  an  interesting  epidemic  of  measles  occurring  in 
Hagelloch,  near  Tubingen,  in  which  188  out  of  197  children  under 
fourteen  years  of  age,  contracted  the  disease.  Seven  of  the  children 
were  under  six  months  of  age  and  all  of  this  number  remained  xcell. 
Of  10  infants  between  six  months  and  one  year,  9  contracted  measles. 
Tiiis-^kperience  would  tend  toshow  that-infants  under  six  mjonths  of 
age  are  very  nuKjli -more  immune  than  those  a  few  mouths  older. 

r]e~13arbillier,"  in  an  epidemic  of  measles  in  the  Foundling  Hospital 
at  Bordeaux,  noted  but  7  cases  among  40  children  under  one  year  of 
age.  Mayr  reports  that  of  10  newborn  and  suckling  infants  exposed 
to  the  disease,  but  1  contracted  it. 

The  susceptibility,  then,  to  measles  is  largely  in  abeyance  during  the 
first  six  months  of  life;  after  this  period  it  gradually  increases  so  that 
after  the  first  year  the  temporary  immunity  has  entirely  vanished. 

Measles  may  in  extremely  rare  cases  be  contracted  during  intra- 
uterine existence,  and  children  may  be  born  with  fully  developed  erup- 
tions. After  careful  search  of  the  literature  Thomas  was  able  to  find 
but  6  properly  authenticated  instances  of  this  occurrence.  Numerous 
authors  refer  to  congenital  measles,  but  the  facts  in  many  cases  render 
the  diagnosis  doubtful.  Several  authors  cited  by  Thomas  record  cases 
which  bear  the  stamp  of  genuineness.  Clarus  reported  to  the  ^Medical 
Society  of  Leipzig  that  he  had  seen  the  eruption  of  measles  quite  plainly 
on  a  foetus  the  mother  of  which  had  died  during  the  exfoliative  stage  of 
the  disease.  Hedrich  speaks  of  a  female  child  born  on  the  fourth  day 
of  an  attack  of  measles  in  the  mother  that  was  covered  with  the  measles 
exanthem  and  had  catarrhal  symptoms,  sneezing,  coughing,  and  inflamed 

1  Beitriige  zur  Pathologie  der  Masern,  etc.,  Tubingen,  1863. 

2  Quoted  by  Thomas,  loc.  cit. 

31 


482  MEASLES 

eyelids.  Vogel,  Guersent,  Hildanus,  Lidelius,  Michaelson,  Seidle, 
Ballantyne,  and  others  have  also  reported  cases  which  in  all  number 
about  20.  The  diagnosis  in  such  cases  could  be  controlled,  as  Thomas 
suggests,  by  noting  the  susceptibility  or  immunity  of  these  children  in 
later  years.  He  reports  an  attack  of  measles  in  a  woman  five  months 
pregnant,  in  which  the  susceptibility  of  the  foetus  was  not  affected,  for 
the  child  contracted  measles  at  the  age  of  nine  years. 

Von  Jiirgensen  says:  "The  poison  must  be  able  to  pass  through  the 
placenta.  It  is  presumed  that  the  child  becomes  infected  very  soon  after 
the  disease  organisms  have  attacked  the  mother,  since  the  disease 
presents  the  same  stage  of  development  in  mother  and  child  at  the  time 
of  the  latter's  birth." 

Hoff,  on  the  other  hand,  states  that  "without  exception  everybody 
born  in  the  year  1846  whose  mother,  according  to  her  own  statement  and 
as  affirmed  by  comparison  with  the  church  records,  contracted  measles 
during  pregnancy,  was  attacked  by  the  disease,  if  exposed  to  it,  at  the 
time  of  the  epidemic  of  1875."  Hoff  states  that  this  was  true  no  matter 
what  month  of  pregnancy  the  mother  happened  to  be  in  when  she  was 
suffering  from  the  measles.  This  experience  throws  a  flood  of  light 
upon  the  question  of  the  placental  transmission  of  measles.  Hoff  draws 
therefrom  the  conclusion  that  "there  is  not  the  slightest  ground  for 
believing  the  contagion  to  be  carried  to  the  foetus  through  the  placental 
circulation." 

Adult  life  offers  no  such  immunity  against  meiE!<sles -as -is  .cobm»©»1^ 
observed  toward  scarlet  fever;  Those  wKo  escape  measles  in  childhood 
do  not  fail  to  take  the  disease  when  exposed  in  later  years.  Measles 
in  adults  is  comparatively  uncommon  only  because  most  persons  have 
suffered  an  attack  in  childhood.  Gregory  states  that  measles  was  absent 
from  the  island  of  Madeira  for  twenty-five  years;  when,  in  1808,  it  did 
invade  the  island,  it  found  almost  the  whole  population  susceptible, 
and  in  four  months  destroyed  700  lives. 

Panum  states  that  in  the  epidemic  of  measles  in  the  Faroe  Island 
in  1846  not  one  person  v/ho  had  escaped  measles  in  the  epidemic  of 
1791  remained  free  of  the  disease.  It  is  evident  that  all  of  these  persons 
must  have  been  over  fifty  years  old.  Measles  may  even  attack  persons 
in  the  decrepitude  of  old  age.  Drake^  in  1844  observed  several  cases 
in  negroes  of  advanced  age,  one  of  them  at  least  eighty  years  old.  Heim 
saw  a  woman  of  seventy-six  years  with  measles,  and  Michaelson  reports 
a  case  in  a  patient  eighty-three  years  old. 

Measles  is  undoubtedly  the  most  common  of  all  of  the  exanthematous 
diseases.  Owing  to  its  extremely  contagious  chai'acter  epidemics  are 
far  more  extensive  and  widespread  than  those  of  scarlet  fever.  While 
large  cities  are  stibject  to  epidemic  outbreaks  from  time  to  time,  the 
disease  seldom  dies  out  altogether.  In  great  centres  of  population  the 
disease  may  be  said  to  be  endemic,  sporadic  cases  developing  every 
now  and  then.     When  the  increase  in  population  by  births  or  other 

1  Drake,  Heim,  and  Michaelson,  all  cited  by  Thomas,  loc.  cit.,  p.  48. 


Till':  I'JTIOLOGY  OF  MI'JASIJ'JS  483 

causes  creates  n  siiflici(;nt  riiiinWor  of  unj)r()l,(;f;tf;(i  .suf>j(;cts  fix;  inf(M;f.ion 
takes  hold  and  an  e})ideniic  results.  Thomas  asserts  that  in  large 
communities  epidemics  mny  be  expected  al)ont  every  two  or  four  years. 
In  small  towns  and  villii,<i!;es  the  interval  of  freedom  is  rriiieh  longer. 

Whitelegge,'  from  a  carcfnl  study  of  English  statistics,  estimates  that 
epidemics  of  measles  aj)pear  about  every  two  years.  About  every  ten 
years  an  epidemic  of  considerable  severity  with  high  death  rate  may 
be  expected. 

In  localities  isolated  by  geographical  position,  such  as  islands  in  the 
ocean,  communities  may  remain  free  from  measles  infection  for  decades, 
a  half-century,  or  for  even  a  longer  period,  (iregory,  writing  in  l'S4.':{, 
says,  "Australia  and  Van  Diemen's  Land  are  to  this  day  exempt  horn 
measles."  When  the  disease  is  once  introduced  into  such  isolated 
communities,  it  finds  almost  the  entire  population  susceptible  and 
smites  with  the  hand  of  a  plague.  It  has  already  been  mentioned  that 
in  the  Fiiroe  Islands,  which  had  been  free  of  measles  for  sixty-five  years 
^11  (il  INK),  (iOOO  out  of  a  population  of  less  than  SOOO  were  attacke7r.'"7'- 

Measles  may,  from  time  to  time,  cover  so  extensive  a  territory  as  to 
become  pandemic,  in  the  same  manner  as  smallpox,  particularly  before 
the  days  of  vaccination.  At  such  times  an  entire  country,  or,  indeed, 
several  countries  may  be  attacked,  llirsch  mentions  a  number  of  such 
general  outbreaks  during  the  century  just  passed.  In  1796-1801  measles 
\vas  present  in  a  large  part  of  England  and  France;  in  1823-24  it  pre- 
vailed extensively  in  Germany,  and  in  1826-28  in  the  Netherlands  and 
Germany.  In  the  two  years  from  1834  to  1836  it  swept  over  the  greater 
part  of  northern  and  middle  Europe.  An  extensive  epidemic  prevailed 
in  1846-47  in  both  the  new  and  the  old  hemispheres.  Since  the  days 
of  rapid  transoceanic  travel  it  is  quite  easy  for  diseases  like  measles  and 
smallpox  to  be  contracted  on  one  side  of  the  ocean  and  to  develop  on 
the  other.  Infectious  diseases  follow  the  channels  of  travel.  ^Measles 
is  not  apt  to  be  carried  by  infected  baggage  or  clothing,  but  by  the  breed- 
ing disease  in  an  exposed  and  unprotected  person. 

Season. — According  to  Gregory  it  was  formerly  believed  that  measles 
began  in  January,  reached  its  crisis  at  the  vernal  equinox,  and  ceased 
in  the  summer  solstice.  Gregory  dissents  from  this  view  and  states 
that  "the  recurrence  and  duration  of  epidemics  are,  in  Europe,  wholly 
irrespective  of  season.  In  Bengal,  however,  measles  never  originates 
except  in  the  cold  season.  Season  affects,  too,  there  the  character  of 
the  symptoms.  In  the  hot  months  the  eruption  is  more  vivid  and  more 
elevated,  and  the  internal  organs  comparatively  but  little  affected.  In 
the  cold  season  the  affection  of  the  mucous  tissues  is  best  developed." 

Hirsch's  figures  show  that  while  measles  most  commonlv  occurs  during 
the  winter  months,  no  season  of  the  year  is  entirely  exempt. 

Three  hundred  and  nine  epidemics  collated  by  Hirsch  began  in  the 
following  months: 

1  British  Medical  Journal,  1893,  vol.  i.  p.  541. 


484  MEASLES 

Three  Hundred  and  Nine  Epidemics  of  Measles  Classified  According 

TO  Season  (Hirsch). 

December     .....    28                          June 19 

January 54                          July 16 

February      .       .       .       .       .14                          August 8 

Winter,  96  epidemics.  Summer,  43  epidemics. 

March 4S  September 16 

April 28  October 34 

May      ■ 23  November 26 

Spring,  94  epidemics.  Autumn,  76  epidemics. 

Thomas  suggests  that  the  lessened  incidence  of  measles  in  mild 
weather  may  be,  in  part,  due  to  the  better  ventilation  of  sick-chambers 
and  the  consequent  diminished  concentration  of  the  infection.  In  cities 
a  much  more  important  cause  of  the  falling  off  of  measles  in  hot  weather 
is  the  closing  of  the  schools.  All  of  the  exanthematous  diseases  in  large 
communities  diminish  during  the  school  vacations  and  increase  upon 
resumption  of  the  sessions  in  the  fall.  There  can  be  no  doubt  that  the 
close  contact  of  children  in  the  schools  is  a  fertile  cause  of  the  spread 
of  the  various  contagious  diseases. 

Contagious  Period. — The  contagious  period  of  measles  may,  in 
general  terms,  be  said  to  last  from  the  beginning  of  the  prodromal 
stage  to  the  complete  disappearance  of  the  eruption.  That  measles 
can  be  communicated  before  the  appearance  of  the  eruption  is  generally 
admitted  by  writers,  and  is  borne  out  by  observation. 

Panum^  details  the  history  of  a  case  in  the  Faroe  Islands  in  which  a 
young  man  had  slept  in  a  bed  with  an  infected  patient  "several  days" 
before  the  rash  broke  out;  fourteen  days  later  the  eruption  of  measles 
appeared  upon  him.  Hoff  reports  an  equally  conclusive  instance  in  the 
case  of  a  clerk  infected  at  Thorshavn. 

Eyre^  reports  an  interesting  and  apparently  conclusive  instance  of 
pre-eruptive  contagion.  A  schoolmaster  at  Beckenham  returned  to  his 
school  on  April  30,  1888,  at  the  end  of  the  Easter  holidays;  he  did  not 
feel  well,  but  continued  his  work  on  May  1  and  2.  He  went  to  bed  on 
the  evening  of  May  2,  and  during  the  night  the  eruption  appeared. 
Although  the  students  were  sent  away,  all  of  the  susceptible  ones — 
fourteen  in  number — contracted  the  disease. 

Ransom^  collected  five  instances  of  measles  infection  conveyed  before 
the  appearance  of  the  rash.  In  two  of  these  cases  the  disease  was 
communicated  two  days  before  the  eruption.  In  a  case  seen  by  Croskey,* 
the  infection  was  believed  to  have  been  transmitted  four  days  before 
the  appearance  of  the  rash.  Holt  reports  a  similar  case  occurring  in 
the  Babies'  Hospital  in  which  the  disease  was  conveyed  four  days  before 
the  eruption  appeared.  On  the  other  hand,  one  of  Ransom's  cases 
failed  to  give  the  disease  to  seven  susceptible  children  exposed  three 
days  before  the  eruption  appeared. 

Measles  is  most  contagious  at  the  height  of  the  eruption.     Indeed, 

1  Virchow's  Archiv,  vol.  i.  p.  499.  "  British  Medical  Journal,  February  23,  1899. 

3  British  Medical  Journal,  January,  1877.  *  Quoted  by  Ransom,  loc.  cit. 


77//';  hrrioiAxiY  of  mJ'JASLK.s  485 

some  writers  contend  that  the  conurninicatioii  of  confiif^ion  is  limitcfl 
to  the  eni])live  stage.  This  is  the  opinion  of  lIofF,  who  h;ul  a  splendid 
opportunity  of  studying  the  Faroe  Islands  cases,  i'anuin  says  it  is 
uncertain  whether  the  catarrhal  and  descjuamative  stages  are  con- 
tagious. Peterson,  a  colleague  of  HofF,  concedes  that  the  catarrhal 
|)eriod  may  be  contagious,  but  denies  that  this  extends  to  the  stage  of 
desquamation. 

We  have  on  several  occasions  had  children  bnjught  into  the  wards  of 
the  Municipal  Hospital  with  the  stains  of  the  measles  exanthem  still 
visible;  although  in  each  of  these  instances  a  score  of  children  were  freely 
exposed,  many  of  whom  were  unprotected  by  previous  atta(;k,  no  cases 
of  measles  developed  among  them. 

There  can  be  no  doubt  that  the  contagiousness  of  measles  is  distinctly 
iii^^il^l^^JJ^^SSjMj^sCH^isquamation.  We  would  be  extremely 
loath~to^assertniowever,  that  it  is  abolished  at  this  time,  and  we  would 
certainly  not  act  upon  the  assumption  that  it  is.  In  the  al)sence  of 
adequate  and  conclusive  data  upon  this  point  it  is  advisable  to  isolate 
measles  patients  until  the  completion  of  desquamation,  or,  at  any  rate, 
for  a  period  of  three  weeks  from  the  commencement  of  the  disease. 

Second  Attacks. — One  attack  of  measles  nearly  always  confers 
immunity  against  subsequent  attacks.  It  is  generally  admitted  by 
careful  and  experienced  observers  that  second  attacks  are  extrouely 
rare.  The  infrequency  of  this  occurrence  may  be  ap})reciated  when  it 
is-^tai£-d^tliat.Maizelis^~!a'as  a,ble  to  find  only  106  instances  of  multiple 
-attaclvs  ill  the  entire  literature  of  the  subject.  (J)f  these  10.3  were  second 
attacks  and  3  were  alleged  to  be  third  attacks.  This  is  an  exceedingly 
-i^«a41r- number,  even  admitting  many  unpublished  cases,  when  the 
universal  extent  of  measles  is  considered. 

Panum,  who  saw  6000  cases  in  persons  of  all  ages  in  the  Faroe  Islands 
epidemic,  did  not  observe  one  instance  of  second  attack.  Rosenstein, 
in  an  experience  extending  over  forty  years,  met  with  but  a  single  instance 
of  the  recurrence  of  measles.  Willan,  in  a  rich  experience  of  twenty 
years,  did  not  see  one  case.  Camby  could  not  recall  one  instance  of 
relapse  or  recurrence  among  700  cases  of  measles.  Thomas'  large 
experience  did  not  include  a  case  and  the  same  may  be  said  of  the 
authorities  quoted  by  him — Berndt,  Theussink,  Schonlein,  ^Mayr,  Schott, 
and  Bartscher.  While  the  experience  of  these  eminent  physicians 
indicates  the  great  infrequency  of  second  attacks,  a  sufficient  number 
of  cases  has  been  reported  to  prove  their  occasional  occurrence. 

Recurrences  may  take  place  a  few  days  to  a  few  weeks  after  the  first 
attack,  in  wdiich  event  one  might  properly  speak  of  a  relapse,  or  they 
may  take  place  months  or  years  later,  constituting  true  second  attacks. 
Relapses  have  been  reported  by  a  considerable  number  of  observers.^ 

1  Ueber  die  durch  das  Ueberstehen  vou  Infectionskrankheiten  Immuiiitiit,  Virchow's  Archiv,  vol. 
cxxxvii.  p.  46S. 

-  Among  those  who  have  reported  relapses  of  measles  may  be  mentioned  Van  Diezeu,  Battersey, 
Robediere,  Flemming,  de  Haen,  Haartman,  Webster,  Kassowitz,  Stiebel.  Brunzlow,  Luithlen, 
Mauthuer,  Kierulf,  Trojanowsky,  Home,  Lewin,  Gauster,  Karg,  Behier,  Tresling,  Spiess,  Feltz, 
Lemoine,  Vergeley,  Fischer,  Roger,  and  others. 


/ 


486  MEASLES 

v.The  relapses  commonly  occur  from  two  to  four  weeks_af]fceiLihefirst 
.  attack.  Thomas  believes  most  of  these  cases  to  ibe'3ue  to  autoinfection 
similar  to  the  relapses  of  typhoid  fever.  Lippe,  who  saw  fifteen  relapses 
in  three  epidemics,  claims  that  the  children  contracted  the  second  attack 
three  or  four  weeks  after  the  first,  from  contact  with  another  case  of 
measles.  In  quite  a  number  of  reported  cases  the  relapse  has  developed 
immediately  after  the  completion  of  the  course  of  the  original  attack. 
It  is  not  uncommon  for  the  second  attack  to  be  inversely  proportionate 
in  gravity  to  the  severity  of  the  first.  SeidP  reports  three  malignant 
recurrences,  two  of  which  ended  fatally. 

Second  attacks  proper  may  occur  from  two  or  three  months  to  twenty 
years  or  more  after  the  first  illness.  Gregory  states  that  Dr.  Baillie 
reported  7  instances  of  recurring  measles,  5  of  which  occurred  in  one 
family;  4  had  second  attacks  after  an  interval  of  six  months,  and  1  at 
the  end  of  twenty-one  years.  Webster^  published  3  cases  in  which  the 
intervals  were  two,  four,  and  six  years  respectively. 

The  list  of  reported  instances  is  quite  a  long  one  and  includes  cases 
published  by  most  reliable  writers. 

Several  apparently  authentic  instances  of  third  attacks  of  measles  are 
on  record.  Van  Diezen,^  of  Antwerp,  published  an  account  of  three 
successive  attacks  in  a  child  three  years  of  age.  The  first  attack  occurred 
early  in  February,  the  second  on  March  4th,  and  the  third  on  April  12th. 
The  attacks  were  well  marked,  the  last  being  preceded  by  vomiting  and 
convulsions.  All  were  followed  by  a  branny  desquamation.  Hennig* 
relates  having  attended  a  woman  during  two  attacks  of  measles  at  the 
age  of  thirty-two  and  thirty-three  years  respectively,  who  had  had  in  all 
probability  an  attack  at  the  age  of  thirteen.  Cases  have  also  been 
reported  by  Drysen,  Bierbaum,  Spiess,  Home,  and  Streng,  although 
Thomas  is  of  the  opinion  that  the  facts  in  the  most  of  these  cases  are 
not  entirely  convincing.  The  probabilities  are  that  many  cases  of  alleged 
multiple  attacks  have  represented  an  error  of  diagnosis  in  one  of  the 
illnesses. 

The  eruption  of  measles  may  at  times  be  so  closely  simulated  by 
that  of  rubella  that  an  error  may  very  readily  be  made.  Histories 
given  by  patients  are  not  authentic  in  determining  the  character  of  an 
illness  long  past.  The  experience  of  such  men  as  Willan,  Panum, 
Rosenstein,  and  Thomas,  which  is  in  accord  with  that  of  most  of  the 
careful  observers,  teaches  that  second  attacks  of  measles  are  exceedingly 
rare. 

The  view  is  held  by  some  veterinarians  that  measles  may  attack 
certain  of  the  lower  animals.  Behla,"  of  Luckau,  Germany,  claims  to 
have  produced  in  a  young  pig  a  disease  closely  resembling  measles  by 
inoculating  the  nose,  mouth,  and  throat  with  mucus  from  the  nose  and 
mouth  of  a  child  suffering  from  measles.     Four  days  later  the  pig 

1  Cited  by  Thomas,  loc.  cit.  2  Med.  Chirurg.  Trans.,  vol.  xxii.  p.  245. 

3  Bull.  g6n.  de  tli6r.,  September  15,  1848,  p.  239. 

*  Exanthematica,  Jahrbuch  fiir  Kinderheilkunde,  new  series,  vol.  viii.  p.  417. 
5  Centralblatt  f.  Bakt.  uad  Parasit.,  xx.,  16  and  17  ;  quoted  by  Williams,  Twentieth  Century 
Practice  of  Medicine,  p.  123. 


77//';  HYMI'T()MAT()I/)(JY  OF  Mf'JASLES  487 

developed  a  discharging  nose  and  congested  and  watery  eyes.  <^)ri  the 
fifth  (lay  the  animal  was  sick,  had  a  ternjKTaturcof  lO.T  V.,  shivered,  and 
refused  food.  On  the  eighth  (Jay  tlie  non-hairy  portions  of  the  face 
showed  red  spots,  which  spread  in  another  day  over  tiie  body,  being 
followed  by  a  mild  desquamation.  Two  pigs  that  had  been  exposed  to 
the  first  one  developed  similar  symptoms  in  the  course  of  two  weeks. 
The  attendant  regarded  the  disease  as  swine  fever,  but  examination  of 
the  blood  and  mucus  failed  to  show  the  presence  r^f  the  bacilhis  found 
in  this  disease. 

Josias^  failed  to  confirm  the  results  obtained  by  Behla,  but  succeeded 
in  communicating  the  disease  to  monkeys.  Chavigny^  also  ob.served 
measles  in  a  monkey. 

THE  SYMPTOMATOLOGY  OF  MEASLES. 

Incubation  Period. — The  incubation  stage  of  measles  may  be  said  to 
be  the  period  elapsing  between  the  date  of  infection,  which,  in  most  cases, 
is  the  time  of  initial  exposure  and  the  development  of  febrile  symptoms. 
In  the  maj^ri^y  "^  cflgpg  ih\^  stage  is  in  the  neighborhood  of  ten  ilay^; 
tJif  eruptipn  ngiifl11y-a.p|ap.iLr-g  nn  qx  about  the  fourteenth  day.  It  is  only 
possible  to  accurately  determine  the  duration  of  the  incubation  stage  in 
cases  in  which  the  exposure  has  been  but  once  and  for  a  brief  period. 

While  persons  susceptible  to  measles  will  ordinarily  take  the  disease 
upon  first  contact,  this  is  not  invariably  the  case.  Where  there  has  been 
prolonged  exposure  it  is  not  possible  to  accurately  fix  the  time  of 
infection. 

Some  writers  speak  of  tlie  incubation  period  of  measles  as  about 
fniirtep.D  days-  In  such  a  statement  there  is  either  an  inaccuracy  of 
.time  or  terms.  The  incubation  period  ceases  when  the  usual  symptoms 
of  measles  manifest  themselves.  While  there  is  a  decided  variability 
in  the  duration  of  Jlie_symptoms  preceding  the  eruption,  we  are  not 
justified  in  speaking  of  the  incubation  periodas  extending  to  the  appear- 
ance of  the  eruption. 

In  general  terms  it  may  be  said  that  the  incubation  stage  of  measles 
is  fl.bnnt  jp.n  nr  p.lp/^^p.n.  dfl,y-q.  Thejieiiad-from  exposure  to  the  develop- 
ment of  the  rash_is..atbouA-io'U3^.te€in-days.  The  incubation  period  in  this 
disease  iS-Su1(3J.eet  to  less  variation  than  in  scarlet  fever,  rubella,  or  chicken- 
^x.  Panum  had  a  spleiictid  opportunity  of  studying  the  incubation 
period  in  the  Faroe  Islands  epidemic.  He  reports  about  40  cases,  in  all 
of  which  the  ^riodJiXlhe-appearance  of  the  rash  was  thirteen  or  fourteen 
days.  The  facts  in  these  cases  are  thoroughly  reliable,  the  date  of 
exposure  having  been  accurately  determmed  in  each.  Smith  and 
Dabney^  report  an  outbreak  of  measles  in  an  institution  in  Virginia, 
in  which  the  disease  developed  in  twenty  children  just  eleven  days  after 
the  rash  appeared  in  the  first  patient.  Spiess*  estimated  the  time 
elapsing  between  the  appearance  of  eruptions  in  the  infecting  and 

1  La  m4d.  mod.,  1898,  No.  29.  -  Bull.  med.  de  Paris,  1S9S,  xii.  p.  334. 

s  Quoted  by  Holt,  loc.  cit.  *  Cited  by  Thomas,  loc.  cit. 


488  MEASLES 

infected  patients  in  147  cases.  In  117  cases  the  interval  was  between 
ten  and  fourteen  days,  in  8  cases  it  was  nine  days,  and  in  22  cases  it  was 
between  fifteen  and  eighteen  days.  Salzman^  found  the  interval  between 
the  eruptions  in  25  cases  infected  from  a  single  patient  to  be  as  follows : 
In  3  cases  it  was  nine  days,  in  8  cases  ten  days,  in  13  cases  eleven  days, 
and  in  1  case  twelve  days. 

Holt^  has  collected  a  series  of  144  cases,  of  which  25  were  his  own,  in 
which  the  incubation  period  could  be  traced  definitely.  The  periods 
were  as  follows:  Incubation  of  less  than  nine  days,  3  cases;  incubation 
of  nine  or  ten  days,  22  cases;  incubation  of  eleven  to  fourteen  days, 
15  cases;  incubation  of  fifteen  to  seventeen  days,  19  cases;  incubation  of 
eighteen  to  twenty  days,  5  cases. 

In  66  per  cent,  of  the  cases  the  incubation  was  between  eleven  and 
fourteen  days,  and  in  but  1  case  was  it  under  a  week.  There  have  been 
cases  in  which  the  incubation  period  has  been  but  five  days,  but  such 
instances  must  be  exceedingly  rare.  On  the  other  hand,  unusually  long 
periods  are  on  record.  Roux^  observed  a^n  epidemic  of  measles  that 
.developed-  a^nong  a  jQuniber  ,of  people  on  shipboard  after^  the  vessel- 
— was  seventeen  days  out  o£ -pert;  no  case  of  measles  had  previously 
existed  among  those  on  board. 

While  it  is  seen  that  some  variability  exists  in  the  incubation  period 
of  measles,  it  will  be  found  in  the  majority  of  cases  to  be  in  the  neighbor- 
hood of  ten  or  eleven  days. 

While  the  incubation  stage  is  generally  devoid  of  symptoms,  patients 
occasionally  feel  unwell  and  complain  of  lassitude,  headache,  malaise, 
etc.,  during  the  latter  part  of  the  period.  Gregory  says:  "Sometimes 
the  entire  incubation  stage  is  marked  by  languor,  lassitude,  and  a  sense 
of  malaise  and  occasionally  a  characteristic  symptom  such  as  cough." 

Prodromal  or  Invasive  Period. — In  those  cases  in  which  the  latter 
days  of  the  incubation  period  are  marked  by  mild  constitutional  disturb- 
ances the  invasive  stage  comes  on  insidiously.     It  is  rather  uncommon 
,  for  measles  to  be  ushered  in  abruptly  with  high  fever.     The  onset  is 
...more  gradual  and  characterized  by  less  intensity  than  that  of  scarlet 
-fever.     Convulsions  and  vomiting  are  rare  occurrences.     The  mucous 
membranes  are  early  attacked,  giving  rise  to  symptoms  which  have 
caused  this  period  to  be  known  as  the  iiatarr-hal-gta>ge.     The  eyes  are 
reddened  and  watery,  sensitive  to  light,  and  often  show  puffiness  of  the 
lids.     The  nose  at  first  feels  obstructed,  but  soon  a  discharge  issues 
therefrom,  accompanied  by  repeated  sneezing.    Occasionally  nose-bleed 
occurs,  but  this  is  seldom  severe.     In  pronounced  cases  the  face  may 
present  a  pufl^y  and  swollen  appearance.    The  involvement  of  the  larynx 
and  trachea  gives  rise  to  hoarseness  a^d  to  a  dry,  hjrd^  and-high-pitchfid 
..,££aigh.    At  times  the  throat  is  sore,  exhibiting'^upon  inspection  redness 
and  swelling  of  the  tonsils,  soft  palate,  and  pharynx.     The  constitutional 
symptoms  consist  of  fever,  headache,  loss  of  appetite,  drowsiness,  and 
irritability.    Somnolence  is  often  a  prominent  feature.     Chills  are  rare, 

1  Cited  by  Thomas,  loc.  cit.  2  Diseases  of  Infancy  and  Childhood,  New  York,  1899,  p.  911. 

3  Quoted  by  Thomas,  loc.  cit. 


PLATE  XLVIL 


Fig.   I. 


'ig-  2. 


Fig.  3. 


Fig. 


The  Pathognomonic  Sign  of  Measles  (Koplik's  Spots). 

^^•^^  1-  The  discrete  measles  spots  on  the  buccal  or  labial  mucous  membrane,  showing  the  isolated 
rose-red  spot,  with  the  minute  bluish-white  centre,  on  the  normally  colored  mucous  membrane. 

Fig.  2. — Shows  the  partially  diffuse  eruption  on  the  mucous  membrane  of  the  cheeks  and  lips;  patches 
of  pale  i)ink  interspersed  among  rose-red  patches,  the  latter  showing  numerous  pale  bluish-white  spots. 

Fig.  3.  The  appearance  of  the  buccal  or  labial  mucous  membrane  when  the  measles  spots  completely 
coalesce  and  give  a  diffuse  redness,  with  the  myriads  of  bluish-white  specks.  The  exanthema  on  the  skin 
is  at  this  time  generally  fully  developed. 

Fig.  4.— Aphthous  stomatitis  apt  to  be  mistaken  for  measles  spots.  Mucous  membrane  normal  in  hue. 
Minute  yellow  points  are  .surrounded  by  a  red  area.      Always  discrete. 


Tlir<:  SYM/'T()MAT()I/)(;V  OF  M/'JASfJ'JS 


489 


occiirriiifi;,  ;i,('Cor(lin<^  (o  Zi(Mr),s,S(;n  and  KniMcr,  only  five  limes  in  ''>\\ 
cases  studied  by  tlicin.  'I'lie  bowfds  arc  iisnjdiy  conslipjilcd,  idtlioiif^li 
occasionally  a  slight  diarriura  is  ()l)serv('d. 

3.^hejeyer  does  not,  ol)serv<;  any  set  standard,  hut  ia  subject  to  con- 
._sideral)le  variation.  Ju  some  cases  it  rises  rapidly  fJuring  tbe  first 
i3Vuiaty-fonr  Iionrs,  reaching  by  eveniiif,'  102°  to  lO.T  F.  On  tlie  morning 
of  the  se<'()n<l  day,  or  occasionally  tli(^  lliird,  tlie  temperature  may  decline 
to  normal  or.tllL'reaboiils,  aceouipanied  by  an  imprf)vement  in  all  of  the 
symptoms.  After  this  i-emission  the  lem|)erafnre  again  begins  to  rise,. 
usually  on  the  eveninjj;  of  the  third  day,  eoiitiuuiiifj  its  ascent  on  the 
Tbiirth  dayTwi th  the  a])])earanee  of  the  eruption.  In  otlier  cases  the  fever 
is  very  moderate  at  the  outset,  not  exceeding  101°  V.  A  grarhjal  increase 
in  the  temperature  and  in  the  catarrhal  symptoms  occurs  up  to  the 
appearance  of  the  rash.  J.o  ,some  epidemics  the  prodromal  symptoms 
are  so  mild  as  to  escape  tlie  observation  of  the  parents  of  the  patient, 
"who  then  asseiTlTie  eruption  to  be  the  first  symptom.  On  the  other 
hand,  there  are  epidemics  in  which  measles  develops  abruptly  with  liigh 
fever  in  such  a  manner  as  to  disguise  the  oncoming  disease  until  the 
appearance  of  the  rash  solves  the  diagnosis. 

In  the  average  case  of  measles  the  invasive  period  lasts  about  four 
days;  there  are,  however,  numerous  exceptions  to  this  duration,  par- 
ticularly in  infants.  Holt  made  notes  of  the  duration  of  the  invasive 
stage  in  270  cases.    His  figures  are  appended: 


One  day  or  less 

.    35  cases. 

Six  days 

.    20  cases. 

Two  davs 

.    47      " 

Seven  days    . 

.      6      " 

Three  days    . 

.     64      " 

Eight  days    . 

.      2      " 

Four  days 

.     64      " 

Nine  days 

.      2      ■' 

Five  days 

.     29      " 

Ten  days 

.     1  case. 

Enanthem,  or  Mucous-membrane  Eruption. — It  is  a  proved  observa- 
tion that  the  eruption  of  measles  may  be  seen  on  the  mucous  membrane 
of  the  mouth  in  advance  of  its  appearance  on  the  cutaneous  surface. 
Xl£a3iin.QJldy,  on  the  second,  day,  inspection  of  the  mouth  will  disclose 
tt]e  presence  of  an  enanthem.  The  presence  of  a  mucous-membrane 
eruption  was  recognized  by  physicians  in  the  early  part  of  the  nineteenth 
century,  as  is  evidenced  by  the  writings  of  ^Villan,  Heim,  and  others. 
Most  of  these  and  later  observers  have  described  the  enanthem  as 
consisting  of  dark-red  or  light-red  spots. 

Flindt^  in  1880  described  the  enanthem  of  measles  in  a  most  accurate 
and  detailed  manner.  He  says:  "The  eruption  consists  of  round  or 
somewhat  irregularly  shaped,  light-red  spots,  not  very  distinctly  circum- 
scribed, and  only  just  raised  above  the  level  of  the  mucous  surface.  The 
spots  vary  in  size  from  a  pinhead  to  a  lentil,  are  in  part  isolated  and  in 
part  collected  into  groups,  quite  irregular  in  shape,  and,  in  some  places, 
coalescent.  At  the  centre  of  the  small  red  spots,  and  giving  them  a 
peculiar  appearance,  are  situated  numbers  of  tiny,  whitish,  shiny,  raised 
points,  apparently  vesicular  in  character  and  irregularly  grouped  accord- 
ing to  the  arrangement  of  the  spots  on  which  they  lie.     These  tiny 

1  Reports  of  the  Danish  Board  of  Health,  translated  and  cited  by  von  Jiirgeiisen. 


490 


MEASLES 


miliary  vesicles  can  be  both  seen  and  felt  as  distinct  elevations.  The 
palpebral  conjunctiva  is  reddened  throughout,  and  besides  the  net-like 
injection  dependent  on  the  distribution  of  its  blood  supply  it  sometimes 
appears  spotted  and  covered  with  miliary,  pearl-covered,  raised  points, 
similar  to  those  on  the  mucous  membrane  of  the  palate. 

"Similar  groups  of  spots  and  vesicles  can  now  also  be  perceived  on 
the  mucous  membrane  of  the  cheeks,  especially  on  the  parts  correspond- 
ing to  the  space  between  the  upper  and  lower  molar  teeth." 


Fig.  79 


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A  case  of  measles  in  a  child  three  and  one-half  years  of  age,  developing  in  the  Municipal 
Hospital ;  temperature  record  from  the  first  day  of  illness. 

The  measles  enanthem  has  been  carefully  studied  in  recent  years  by 
Filatow  (1895),  Canby  (1895),  and  Koplik  (1896).  The  last-named 
physician^  describes  the  mucous-membrane  eruption  as  follows:  "If 
we  look  in  the  mouth  at  this  period  (invasion)  we  see  a  redness  of  the 
fauces;  perhaps,  not  in  all  cases,  a  few  spots  on  the  soft  palate.  On 
the  buccal  mucous  membrane  and  inside  of  the  lips  we  invariably  see 
a  distinct  eruption  which  consists  of  small,  irregular  spots  of  a  bright- 

1  Archives  of  Pediatrics,  December,  1896,  vol.  xiii.,  and  Medical  Record,  New  York,  1898. 


PLATE  XLVIir. 


Patient  with  Measles  Exhibiting  Eruption  and  Catarrhal 
Inflanin-iation  of  tlie  Eyes. 


Tllli  HYMI'TOMATOI/XIY  OF  M/'JASfJ'JS  491 

red  color.  In  the  centre  of  each  spot  there  is  noted,  in  strong  daylight,  a 
minute,  hlidsh-ivhite  speck.  These  red  spots  with  aeeornpanying  sfjceks 
of  a  })hiish-white  eolor  are  ahsohjtely  j)atliogiionioi)if-  of  beginning 
measles,  and  when  seen  can  be  relied  upon  as  a  forerunner  of  the 
erui)tion.  No  one  has  to  my  knowledge  called  attention  to  the  pathog- 
nomonic nature  of  these  small,  bluish-white  spots.  Sometimes  only  a 
few  red  spots  with  this  central  bluish  point  may  exist — six  or  more; 
in  marked  cases  they  may  cover  the  whole  inside  of  the  buccal  mucous 
membrane. 

"The  eruption  just  described  is  of  greatest  value  at  the  very  outset 
of  the  disease,  the  invasion.  As  the  skin  eruption  begins  to  appear  and 
spreads,  tlie  eruption  on  the  mucous  membrane  becomes  diffuse  and 
the  characters  of  a  discrete  eruption  disappear  and  lose  themselves  in 
an  intense  general  redness.  AVhen  the  skin  eruption  is  at  the  efflorescence 
the  eruption  on  the  buccal  mucous  membrane  has  lost  the  character  of 
a  discrete  spotting  and  has  become  a  diffuse  red  background,  with 
innumerable  bluish-white  specks  scattered  on  its  surface.  The  mucous 
membrane  retrogrades  to  the  normal  appearance  long  before  the  erup- 
tion on  the  skin  has  disappeared." 

Koplik  also  speaks  of  irregularly  shaped,  rose-colored  spots  and 
streaks  which  are  commonly  seen  on  the  hard  and  soft  palate  and  also 
on  the  cheeks.  They  present  small,  whitish,  punctate,  miliary  vesicles. 
Koplik  states  that  the  rose-colored  papules  or  streaks  with  super- 
imposed miliary  vesicles  are  found  in  rotheln,  scarlet  fever,  and  some 
cases  of  simple  angina,  but  the  reddish  spots  with  bluish-white  specks 
in  their  centres  occur  only  in  measles. 

Subsequent  observations  have  confirmed  the  claims  as  to  the  pathog- 
nomonic nature  of  these  spots.  They  do  not  appear  to  be  present  in 
any  other  disease.  We  have  examined  the  mouth  in  many  cases  of 
rubella  and  have  noted  the  presence  of  red  spots  similar  in  appearance 
to  those  seen  on  the  skin,  but  we  have  never  seen  such  spots  surmounted 
by  bluish-white  specks  as  occur  in  measles. 

Filatow  speaks  of  a  desquamation  of  the  epitheliimi  of  the  mucous 
membrane  of  the  lips  and  cheeks  in  the  form  of  whitish  shreds. 

Baginsky  noted  desquamation  on  the  gums  in  the  form  of  whitish 
patches  and  thought  this  appearance  to  be  characteristic  of  measles. 
We  have  repeatedly  noted  the  presence  of  these  whitish  patches  on  the 
gums  in  scarlet  fever. 

The  presence  of  the  measles  enanthem  is  of  great  diagnostic  value; 
its  absence  has  a  less  important  negative  evidence  because  in  a  small 
proportion  of  measles  cases  the  spots  are  not  present.  We  have  seen 
a  small  proportion  of  cases  of  measles  in  which  the  Koplik  spots  were 
absent.  Of  187  cases  of  measles  examined  by  Cotter^  at  the  New  York 
Foundling  Hospital,  169  showed  the  characteristic  spots.  In  8  patients 
the  spots  were  absent,  while  in  10  patients  their  presence  was  doubtful. 
In   78   cases   the   spots   appeared   synchronously  with   the   cutaneous 

1  Archives  of  Pediatrics,  1900,  xTii. 


492  MEASLES 

eruption;  in  88  cases  the  spots  preceded  the  eruption  by  one  to  five  days; 
in  2  cases  the  spots  did  not  appear  until  after  the  rash. 

Lorand^  studied  the  incidence  of  Kophk's  spots  in  two  series  of  cases 
of  measles,  numbering  in  all  523.  The  spots  were  absent  in  30  cases 
out  of  this  number. 

Pre-eruptive  Rashes  in  Measles. — In  almost  all  of  the  exanthematous 
fevers  the  true  specific  eruptions  may  be  preceded  by  accidental  rashes. 
Measles  is  no  exception,  although  prodromal  erythemata  in  this  disease 
are  rare. 

Meredith  Richards^  says:  " In  the  pre-eruptive  stage  of  measles  there 
inay  be  a  scarlatiniform  rash,  usually  more  transient  and  more  diffuse 
than  the  eruption  of  scarlatina.  This  rash  is  responsible  for  some  of 
^the  cases  in  which  measles  is  diagnosed  as  scarlet  fever.  Another  pre- 
eruptive  accidental  rash  is  a  somewhat  faint  general  erythema,  not 
unlike  the  true  measles  eruption  in  its  general  appearance,  but  almost 
confined  to  the  trunk  and  limbs,  and  more  diffuse  and  less  distinctly 
papular. 

Roger''  records  5  cases  of  prerubeolic  erythema  occurring  among 
1917  cases  of  measles.  These  developed  in  an  infant  of  fourteen  months, 
a  child  of  three  years,  and  three  adults,  and  appeared  two  or  three  days 
before  the  time  of  the  measles  eruption.  We  recall  a  young  girl,  aged 
fourteen  years,  in  whom  a  partial  scarlatiniform  erythema  of  con- 
siderable intensity  developed  upon  the  neck,  face,  and  upper  part  of 
the  chest,  on  the  second  day  of  the  febrile  symptoms,  .  The  symptoms 
suggested  at  first  an  atypical  scarlatina.  The  rash  disappeared,  however, 
in  about  thirty-six  hours,  and  twelve  hours  later,  on  the  fourth  day  of 
the  illness,  the  eruption  of  measles  appeared.  Gerhard t*  observed  a 
prodromal  exanthem  in  the  femoral  triangle  which  appeared  a  day 
before  the  measles  eruption.  Comby"*  records  2  cases  of  pre-eruptive 
rashes.  A  girl,  aged  four  and  a  half  years,  developed  at  the  beginning 
of  the  invasive  stage  of  measles  a  scarlatiniform  eruption  which  persisted 
throughout  the  18th  and  19th  of  July,  the  true  measles  exanthem  appear- 
ing on  July  22d.  Another  child  of  the  same  age  was  admitted  to  the 
hospital  on  July  20th  with  a  morbilliform  rash ;  on  July  22d  the  measles 
eruption  appeared. 

The  cause  of  these  accidental  rashes  cannot  be  readily  assigned.  In 
most  of  Roger's  cases  the  rashes  were  morbilliform;  it  is  possible  that 
these  represent  abortive  attempts  of  the  true  eruption  to  appear  before 
the  usual  time.  Thomas  says:  "The  earliest  signs  of  the  eruption,  at 
first  in  a  thoroughly  undeveloped  condition,  appear  not  infrequently 
upon  the  first  day  of  the  febrile  period,  more  often  on  the  second  or 
third."  The  scarlatiniform  rash,  whatever  may  be  the  cause,  is  of 
importance  because  of  errors  of  diagnosis  which  its  presence  may 
occasion. 

1  Jahrbuch  f.  Kinderheilk.,  1901,  iii.  p.  658. 

3  Accidental  Rashes  Occurring  in  the  Course  of  the  Exanthemata,  Quarterly  Medical  Journal 
1898,  vol.  V.  p.  31. 
3  Les  maladies  infectieuses,  Paris,  1902,  p.  874. 
*  Quoted  by  Thomas.  '  6  Trait6  des  maladies  d'enfance,  Paris,  1897. 


77/ A'  HYMPTOMATOr/KlY  OF  M /'JASfJ'J.'i  493 

The  Eruptive  Period.-  TIk;  iih;i  I(  <  xantlicin  usually  appears  upon 
f,li('  foil  rill  (|;iy  of  the  febrile  disorder.  It  does  not  Invarlaltly  appear 
ill  one  |»;ii(i(id;ir  locality,  as  sonu;  writers  siufc.  TIk-  most  erunnion 
initial-sLtcs  arc  llic  side  of  neck,  llic  maslold  i(;:i'.ii  'if  il,.-  temples  and 
fronlal  border  of  hair,  tlic  cliecks,  and  the  chin  in  oUi(;r  words,  about 
(lie  face  and  neck.  Tlic  ciiipiion  of  measles  has  a  spLTJal.  [i rc.( I i leclioii 
for  the  iacfi^JSKhich  is  earlier  and  n)ore  copiously  covered  than  other 
areas. 

JLt  is  n<»t  uncommon  for  tlu;  eruption  in  this  region  to  become  c.OJi- 
Jluent  and  to  ^ive  rise  to  a  dusky  turgesccnec  of  the  skin.  From  the  face 
and  neck  the  rash  rapidly  extends  over  die  liiink  and  upper  extrem- 
ities. Xlie  lower  extremities  are  the  last  and -least  intensely  attacked; 
Qomrnonly  but  a  few  scattered  lesions  are  seen   upon   the   legs. 

Aitken^  descril)es  the  measles  eruption  as  apj)earing  in  three  crops. 
The  first  crop  appears  on  the  face,  neck,  and  upper  extremities,  on  the 
third  or  fourth  day  of  the  disease;  on  the  following  day  the  second  crop 
covers  the  trunk,  and  on  the  third  day  the  third  crop  appears  on  the 
lower  extremities. 

Character  of  the  Eruption.^ — ^The. e:ssential  lesion  of  measles  is  a 
slightly  elevated  macule;  it  is  sufficiently  elevated  to  Ije  recognized  Tjoth 
by  the  sense  of  sight  and  touch.  The  more  circumscribed  the  lesion  is 
the  more  is  it  distinctly  papular,  and  the  more  diffuse  and  confluent 
tlie  eruption  is  the  more  does  it  approach  an  erythematous  and  un- 
elevated  efflorescence.  The  macules,  vary  greatly  in  size  from  a  pin- 
bead.  to~a  "bean  or  finger-nail.  They  are  irregular  in  outline,  being  at 
times  rounded  or  oval,  but  at  other  times  angular,  indented,  and  spun 
out.  They  are  usiially  sharply  marginated  and  stand  outsharply  against 
the, pale,  integumentary  background. 

To  the  fingers  passed  over  the  lesions  a  soft  or  velvety  feel  is  imparted, 
ouitejanlike  the Jj^  feel  of  the  early  sinallpox  eruption.     The 

color  of  the  measles  exanthem  varies  in  dift'erent  patients  and  at  different 
stages  in  the  same  individual.  Itis^^aeldom  as  vivid  a  red  as  is  seen  in. 
the  exanthem  of  scarlatina.  The  macules  in  the  beginning  have 
■''coinnu)nly  been  compared  M'ith  the  appearance  of  flea-bites;  they  are 
of  a, dull-red  color,  not  infrequently  becoming  duskyi  Tii  'some  patients 
flie  eruption,  particularly  when  it  becomes  confluent,  has  a  distinct 
bluish  tinge.  The  bluish  coloration  is  not  at  all  uncommon  upon 
dependent  areas  such  as  the  back.  In  pronounced  cases,  particularly 
in  adults,  the  face  may  exhibit  an  extremely  dusky-red  appearance,, 
whigJv-with  a  slight  swelling  of  the  skin, ' produces  a  strange  and  dis- 
Sgiuucing  tm-gescence. 

On  the  first  day  of  the  eruption  the  lesions  are  small  and  discrete, 
in  many  cases  bearing  a  resemblance  to  the  eruption  of  rubella.  The 
macules  subsequently  enlarge  in  size  and  in  number,  coalesce  in  areas, 
^an"(i"produce  a  rash  which  is  essentially  blotchy.    The  arrangement  of^ 

ie^easleslesions  lacks  symmetry  and  uniformity.     At  times  distmct 

1  The  Science  and  Practice  of  Medicine,  1868,  p.  288. 


494 


MEASLES 


crescents  and  segments  of  circles  can  be  distinguished;  at  other  times 
such  configurations  are  absent.  The  rash  of  measles  does  not  invariably 
consist  of  slightly  elevated,  velvety  macules.  There  are  at  tini^S-dJslinct 
papules  present,  and  miliary  vesicles  are  not  infrequently  seen.-- 

Mayr,  in  his  article  on  "Measles"  in  Hebra's  Diseases  of  the  Skin 
(1866),  distinguishes  a  number  of  varieties  of  measles  based  upon  the 
character  of  the  eruption.  The  term  morhilli  Iceves  is  applied  to  the 
common  form  in  which  the  character  of  the  eruption  is  smooth  and  flat, 
the  individual  macules  being  separated  by  areas  of  healthy  skin. 

In  morhilli  papulosi  there  appear  dark-red  or  reddish-brown  points 
or  papules,  the  size  of  millet  or  hemp  seed,  situated  at  the  mouths  of 
hair  follicles.  This  form  of  measles  is  said  to  occur  in  certain  epidemics, 
taking  the  place  of  the  more  usual  variety. 

We  have  known  the  papular  form  to  be  confounded  with  smallpox 
otT  more  than  one  occasion. 

Fig.  : 


Measles  exanthem  on  the  third  day  of  the  eruption  and  the  seventh  day  of  the  disease. 

^In  morhilli  vesiculosi  or  miliares  small,. pinpoint  to  pinhead-si^ied^-. 
—-vesicles  are  seen  upon  the  summits  of  the  lesions.  This  gives  the  skin 
an  appearance  resembling  prickly  heat,-  and,  indeed,  the  presence  of 
the  miliary  vesicles  has  been  ascribed  to  the  sweating  process.  This 
is  probably  not  the  case,  as  the  vesicles  are  identical  with  those  com- 
monly seen  in  scarlet  fever,  in  which  disease  the  sweating  process  is  in 
abeyance. 

Morhilli  confiuentes  describes  the  form  in  which  the  macules  run 
together  and  become  confluent.  It  will  be  remembered  that  this  was 
ihe  term  applied  to  scarlatina  before  the  days  of  Sydenham. 

We  have  seen  numerous  cases  which  justify  the  use  of  the  term 
confluent  measles.  We  recall  a  very  severe  epidemic  of  measles  which 
prevailed  in  the  scarlet-fever  wards  of  the  Municipal  Hospital  a  few 
winters  ago.  The  eruption  in  these  cases  was  normal  in  the  beginning, 
but  in  a  few  days  became  intensely  confluent  and  vivid  over  the  greater 


TIIM  HYMrrOMATOLOfJY  OF  MKASLES  495 

part  of  the  cutaneous  surface.  The  resemblance  of  tlie  rash  aftf;r  a  few 
days  to  that  of  scarlet  fever  was  strikin^^  although  in  most  every  instance 
there  could  be  found  in  one  region  or  other,  and  commonly  about  the 
buttocks,  [)ale  areas  of  skin  against  which  the  marginate  border  of  the 
confluent  rash  stood  out  in  sharp  contrast.  The  mortality  among  these 
patients  was  very  high. 

Morhilli  hemorrhagicl  is  that  variety  in  which  the  macules  are  puq)lish 
or  bluish  and  from  which  the  color  cannot  be  made  to  disappear  by  the 
pressure  of  the  fingers.  This  condition  is  usually  observed  in  malignant 
cases. 

The  various  lesions  here  described  may  be  seen  to  a  certain  extent  in 
ordinary  cases,  but  the  form  characterized  by  papules,  miliary  vesicles, 
or  confluence  may  each  be  particularly  well  pronounced  in  certain 
epidemics. 

As  regards  the  rapidity  of  extension  of  the  measles  eruption,  Thomas 
observes  that  if  it  appears  early  in  the  invasive  stage  it  is  apt  to  remain 
in  a  moderately  developed  condition  for  several  days  upon  the  face 
alone.  A  more  rapid  evolution  and  spread  occur  when  the  temperature 
begins  to  rise  sharply.  On  the  other  hand,  when  the  exanthem  first 
appears  at  a  late  period,  when  the  fever  is  reaching  the  acme,  the  rash 
spreads  rapidly  over  tlie  body.  The  intensity  of  the  eruption  and  the 
tleu-ree  o!"  the  ivxcr  iiicroiisc  juiri  pas.su.  At  the  l)eginning  of  the  eruption 
fhe  temperature  does  not  register  its  maximum;  it  is  only  after  the  full 
development  of  the  exanthem  that  the  pyrexial  fastigium  is  reached. 
The  temperature  at  this  time  is  commonly  104°  F.,  and  not  infrequently 
105°  F.  The  fever  may  reach  even  a  higher  degree  than  this.  Temper- 
atures of  108°  and  109°  F.  have  been  observed,  and  Hunter^  saw  a  child 
of  sixteen  months  with  a  temperature  of  110°  F.,  the  patient  ultimately 
recovering.  When  the  maximum  fever  is  attained  the  eruption  is  copious 
and  intense;  the  face  is  often  of  a  uniform  dusky-red  color  and  oedematous, 
particularly  about  the  eyelids.  The  entire  body  is,  as  a  rule,  covered, 
not  even  the  palms  and  soles  being  exempted.  Not  infrequently  the 
rash  gives  rise  to  a  considerable  degree  of  itching. 

During  the  development  of  the  eruption,  the  local  as  well  as  the 
constitutional  symptoms  increase  in  intensity.  The  conjunctivge  are  red 
and  swollen  and  an  abundant  mucopurulent  discharge  issues  from  the 
palpebral  cleft,  later  drying  and  gluing  the  lids  shut.  When  the  lids  are 
open  there  is  great  sensitiveness  to  light.  A  similar  profuse  discharge 
from  the  nose  irritates  and  excoriates  the  nostrils  and  upper  lip.  There 
is  commonly  painful  swallowing  and  enlargement  of  the  glands  at  the 
angles  of  the  ]aw.  The  cough  is  frequent  and  harassing,  and  the  voice 
hoarse  and  aphonic.  Evidences  of  bronchitis  are  usually  present  at 
this  time.  The  ear  placed  to  the  chest  will  discover  the  presence  of  dry 
anS  moist  rales.  In  large  children  and  adults  there  is  expectoration  of 
mucopurulent  material.  Children  are  much  prostrated,  manifest  great 
thirst,  refuse  food,  and  are  either  extremely  restless  and  peevish  or 

1  British  Medical  Journal,  April,  1S9S. 


496  MEASLES 

somnolent,  ypmiting^nd  cibdominal  pain  are  1 1  n rom m nn ,  .hjn LdJMrbff «■ 
is  frequent,  the  stools  being  offensive  and  often  slimy.  The  eruptive" 
stage  lasts  ordinarily  four  or  five  days.  With  the  fading  of  the  rash 
there  is  a  gradual  subsidence  of  the  fever  and  the  catarrhal  symptoms. 
_  It  is  rare  for  a  critical  fall  of  temperature  with  sweating  to  occur.  When 
this  does  take  place  there  is  apt  to  be  alarming  prostration.  The  decline 
of  the  fever  is  by  steps,  but  is  nevertheless  moderately  rapid.  Ordinarily 
but  twenty-four  to  thirty-six  hours  elapse  between  the  acme  of  the  fever 
and  the  return  to  normal.  When  the  decline  is  slower  than  this  it  is 
characterized  by  morning  remissions  and  evening  exacerbations.  During 
convalescence  the  temperature  may,  for  several  days,  be  below  the 
normal  line. 

As  the  rash  fades,  the  appetite  improves,  somnolence  and  irritability 
disappear,  and  the  child  begins  to  acquire  its  normal  brightness,  and 
desires  to  leave  the  bed.  The  inflammation  about  the  eyelids  and  the 
mucous  discharges  gradually  improve,  although  the  eyes  may  remain 
sensitive  to  light  for  some  days.  The  hoarseness  and  cough  persist  for 
some  time,  but  in  favorable  cases  improve  from  day  to  day.  Where  no 
bronchial  or  pulmonary  complications  develop  the  patient  is  practically 
well  at  the  end  of  ten  days  or  two  weeks,  but,  of  course,  requires  to  be 
*"  carefully  guarded  against  exposure. 

Stains  (Pigmentation). — As  the  rash  disappears  there  are  left  on  the 
skin  faint  reddish-brown  stains  which  may  be  detected  for  a  number  of 
days.  The  stains  correspond  with  the  size  and  shape  of  the  original 
lesions  and  are  highly  characteristic;  they  are  of  considerable  diagnostic 
value,  and  will  often  enable  one  to  diagnosticate  an  attack  of  measles  after 
it  has  subsided.  When  children  presenting  the  stains  of  the  measles 
exanthem  are  admitted  into  a  hospital  or  other  institution,  they  should 
be  isolated  in  order  that  they  do  not  transmit  the  disease  to  others.  The 
stains  may  persist  for  a  week  or  even  longer. 

Hemorrhagic  Eruption  in  Measles  of  Moderate  Severity. — It  is  not 
rare  for  the  eruption  in  cases  of  measles  of  average  severity  to  exhibit 
hemorrhagic  extravasation  into  the  skin.  The  macules  in  such  cases 
are  of  a  deeper  hue,  varying  from  a  claret  red  to  a  reddish-blue  tint. 
It  is  observed  that  the  spots  do  not  disappear  upon  pressure  of  the 
fingers.  The  hemorrhage  into  the  skin  may  be  noticed  at  the  height 
of  the  eruption,  or  it  may  become  evident  only  during  the  decline,  when 
the  redness  begins  to  fade.  Claret-color  or  bluish  discolorations  are  left 
which  pass  through  the  color  variations  observed  in  an  ordinary  bruise. 
The  discolorations  coincide  in  size  and  shape  with  the  original  measles 
spots. 

_J[t  is  impojtant  to  distinguish  this  benign  form,^hemorrhagic  eruption^ 
from  the  malignant  variety.  In  the  former  the  constitutional  symptoms 
are  not  unusually  severe  and  hemorrhages  do  not  take  place  from  the 
Various  mucous  membranes.  We  have  not  infrequently  noted  hemor- 
rhagic measles  spots  in  cases  of  average  severity,  which  pursued  a 
favorable  course,  terminating  in  recovery.  Holt  observed  hemorrhagic 
eruptions  in  about  5  per  cent,  of  his  cases.  "^  >.«^~,  .,.».«,...>■       :  •»— 


77//';  S)'MI"r()MAT()f/X;Y  OF  MFASLFS  497 

Desquamation  begins  as  tlu;  rii.sli  f.-ulcs  iiwiiy  inid  is  fir,-,(  /irjfc*]  upon 
inili.'u  sites  of  llie  ci'dpiioii,  ii;i,iiH'iy,  (Ik;  tuc(;  uiid  (he  neck,  llie  scaling 
is  braiuiy  ;ui(I  fiirriirjiccous,  and  is  often  ,so  fine  as  to  require  careful 
"scrutiny  (o  obsnvc  il.  'i'he  skin  seldom  comes  off  in  large  flakes  as  it 
does  in  scarlet  icvcr.  'Vlw.  junount  of  des()uair);itif)M  varies  in  difl'erent 
cases  and  is  usually  ])ro|)()rti()nate  to  tlie  intensity  of  the  antec^edent 
eruption.  In  many  [)atients  no  descjuamation  will  be  seen  at  all.  On 
the  trunk  the  perspiration  which  is  common  in  measles  obscures  the 
fine  scales  or  enables  them  to  cling  to  the  body  linen.  The  desquamation 
is  usually  most  observable  on  the  face.  S<"ding  continues  ordinaVily 
from  a  few  days  to  a  week,  but  may  rarely  be  j)rotracted  for  ten  fJays 
or  iwo   weeks. 

Anomalous  Cases  of  Measles. — All  exanthematous  diseases  exhibit  at 
times  variations  from  what  might  be  regarded  as  the  normal  standard. 
Anomalous  cases  of  measles  may  develop  individually  during  the  course 
of  a  normal  epidemic,  or  there  may  be  special  aberrant  features  peculiar 
to  prevailing  forms  of  the  disease.  The  special  predominance  of  the 
papular  element  of  the  eruption  is  more  common  in  certain  epidemics. 
Mayr  says  that  the  Nirlas  or  "Nirles  of  Alibert"  was  mostly  probal^ly 
a  papular  form  of  measles. 

The  chief  deviations  from  the  normal  type  are  those  forms  that 
exhibit  unusual  benignity  or  exaggerated  severity. 

Mild  Measles. — In  rare  cases  there  may  be  an  absence  of  one  or  several 
of  the  important  manifestations  of  the  disease  that  go  to  make  up  the 
characteristic  symptom-complex,  ^hus,  measles  inay  exist  ^^■ithout 
fever,  without  catarrhal  symptoms,  or,  indeed,  without  an  eruption. 
^'Measles  Without  Fever  (Morbilli  sine  febre),  Morbilli  Apyretica. — Leulje 
says:  "Although  there  may  be  very  little  fever  in  mild  cases,  it  is  never 
entirely  absent."  Nevertheless,  von  Jiirgensen^  reports  two  cases  of 
measles  occurring  in  infants  of  four  weeks  and  twenty-one  months  of 
age,  respectively,  who  had  catarrhal  symptoms  and  undoubted  eruptions, 
and  who  had  been  exposed  to  measles,  who  never  had  any  elevation 
beyond  99°  F.  Extremely  mild  and  abortive  cases  of  measles  appear  to 
be  more  common  in  young  infants,  who,  as  has  been  stated,  possess 
only  a  very  limited  susceptibility  to  the  disease. 

Measles  Without  Catarrhal  Symptoms  (Morbilli  sine  catarrho). — The 
absence  of  catarrhal  symptoms  is  occasionally  noted  in  infants  during 
the  prevalence  of  measles  of  the  ordinary  type.  In  such  cases  there  is 
usually  very  little  elevation  of  temperature  and  the  eruption  is  not 
intense.  The  genuineness  of  these  attacks  is  established  not  only  by 
previous  exposure  to  regular  measles,  but  by  the  immunity  conferred 
against  subsequent  attacks.  J.t.. 14. evident  that  when  the  fever  and 
catarrhal  symptoms  are  insignificant  the  case  must  present  considerable 
resemblance  to  rubella.  If  a  disease  prevails  epidemically,  in  which 
these  two  groups  of  symptoms  are  uniformly  in  abeyance,  the  strong 
probabilities  are  that  the  disease  is  rubella  and  not  measles. 

1  Loc.  cit.,  p.  267. 
32 


498  MEASLES 

Measles  Without  Eruption  (Morbilli  sine  exanthemate,  Morbilli  sine 
morbillis). — As  is  the  case  in  sniallpox  and  scarlet  fever,  it  is  possible 
^for  measles  to  occur  without  the  development  of  the  exanthem..  Such 
cases  are,  of  course,  excessively  rare,  but  are  recognized  by  careful  and 
conservative  writers.  Thomas  says  that  the  diagnosis  is  more  often 
made  than  is  justified,  but  remarks  that  "this  form  of  the  disease  may 
be  diagnosticated  in  persons  previously  unattacked,  if  in  a  single  case, 
during  an  epidemic  of  measles,  the  characteristic  mucous  membrane 
synaptoms  together  with  fever  appear  and  become  exactly  as  much 
developed  as  in  measles  with  an  exanthem,  so  that  we  have  ground  for 
assuming  that  this  symptom  alone  is  lacking  from  a  normal  course." 
Cases  may  occur  in  which  the  attack  of  measles  is  typical  up  to  the 
eruptive  stage,  but  at  this  point  the  anticipated  exanthem  fails  to  appear 
and  convalescence  is  established.  Embden^  claims  to  have  observed 
20  patients  among  461  cases  of  measles  in  Heidelberg,  in  whom  the 
eruption  was  absent.  The  cases  were  of  a  mild  type,  but  some  few 
had  severe  complications. 

Rush  makes  mention  of  persons  who  in  1789  presented  the  usual 
manifestations  of  measles,  fever,  cough,  etc.,  but  no  eruption  except 
in  some  cases  a  trifling  efflorescence  about  the  neck  and  breast.  Webster^ 
claims  to  have  seen  similar  cases  in  1773  and  1783. 

Well-authenticated  cases  of  this  kind  are  said  to  have  been  seen  in 
an  epidemic  in  Paris  in  1850.  The  usual  premonitary  symptoms  of 
measles  appeared  in  a  number  of  children;  the  regular  course  was 
followed  in  a  certain  proportion,  but  in  a  number  of  others  some  present- 
ing unequivocal  spots  of  measles  on  the  neck  and  chest,  which  rapidly 
disappeared,  the  lungs  became  quickly  involved.^ 

Rilliet*  reports  a  case  of  severe  measles  without  eruption  in  a  twenty- 
one-month-old  child  who  contracted  the  disease  twelve  days  after  other 
cases  in  the  same  family.  There  were  fever,  coughing,  and  sneezing, 
but  the  eruption  did  not  appear.  On  the  fourth  day  a  lobular  pneu- 
monia developed,  the  child  succumbing  on  the  eighth  day.  Some 
authors  accept  the  statement  that  desquamation  may  occur  in  measles 
without  eruption.  We  contend,  as  in  the  case  of  scarlet  fever,  that 
desquamation  does  not  occur  without  some  antecedent  structural  change 
in  the  skin,  and  that  when  desquamation  occurs  it  signifies  that  a  rash 
has  existed  which  was  unobserved. 

There  are  mild  cases  of  measles  in  which  all  of  the  usual  phenomena 
are  present,  but  in  an  extremely  moderate,  and  sometimes  imperfect, 
degree.  The  maximum  temperature  in  such  cases  does  not  exceed 
102°  F.  and  the  fever  lasts  but  four  or  five  days.  The  eruption  is  faint, 
poorly  marked,  of  short  duration,  and  often  so  indefinite  as  to  require 
other  evidence  to  establish  the  diagnosis.  The  catarrhal  symptoms  are 
also  slight,  but  present  more  uniformity  than  the  cutaneous  manifesta- 

1  Quoted  by  von  Jiirgensen,  loc.  cit.  "        — 

2  Quoted  in  editor's  notes  in  Bulkley's  American  edition  of  Gregory's  Lectures,  1851. 
'  London  Medical  Gazette,  June,  1850,  p.  572  ;  cited  by  Bulkley,  loc.  cit. 

*  Barthez  and  Rilliet,  p.  249  ;  cited  by  von  Jiirgensen. 


77//';  HVMI'TOMATOIJXIY  OF  MI'lASLHH  4!)9 

tions.  This  form  is  ;i,])(,  l.o  Ix^  iiii!itt,(;ii(lc(l  Ity  coniplications  ;ui(l  flic 
prognosis  is  exlixniicly  fav()rjil>l('. 

Severe  and  Malignant  Measles.-  INJcuslcs  of  unusual  severity  may  occur 
in  isolaicd  inslaiiccs  in  ordinary  c|)i(l<Mriics,  or  tJu;  disease  may  prevail 
at  times  in  severe  forni.  The  I'jictors  which  deterniiri(;  ni;dif^n;incy  are 
in  some  instances  weakness,  debility,  and  bad  hygienic  surroundings  of 
the  patient,  and  probably  in  others  an  intense  virulence  of  the  infection. 
There  are  severe  cases  which  are  characterized  by  a  normal  c;fjurse  of 
the  disease,  but  exhibit  an  unusual  intensity  of  all  of  the  symjjtoms. 
The  fever,  catarrhal  symptoms,  and  eruption  may  all  be  excessively 
developed.  In  tlie  severe  and  fatal  epidemic  which  we  observed  a  few 
years  ago  there  was  a  general  tendency  to  intense  confluence  f>f  the 
eruption,  so  that  on  the  second  or  third  day  the  rash  became  cjuite 
scarlatinal  in  appearance. 

In  some  cases  characterized  by  great  initial  severity  the  system  seems 
to  be  overwhelmed  by  the  poison  of  the  disease.  The  temperature 
soars  to  great  height  (105°  to  107°  F.),  there  is  profound  prostration ,  great 
restlessness  alternating  with  stupor,  and  the  patient  succuml)s  })efore 
the  appearance  of  the  rash.  In  these  toxaemic  cases  the  diagnosis  may 
be  extremely  difficult,  and,  unless  elucidated  by  the  history,  quite 
impossible. 

Severity  may  also  be  manifested  by  the  early  development  of  pvbnonari/ 
complications.  The  first  few  days  of  the  invasive  stage  may  be  quite 
normal,  but  suddenly  the  lungs  become  attacked  and  a  fatal  result 
rapidly  ensues. 

In  the  so-called  typhoii  form  of  measles  the  disease  is  ushered  in 
with  high  fever  and  great  prostration.  The  skin  is  hot  and  dry;  there 
is  great  thirst  and  marked  muscular  relaxation.  Nervous  symptoms  are 
pronounced,  the  patient  being  either  apathetic  and  somnolent  or  delirious. 
The  tongue  is  dry  and  furred,  the  lips  glazed,  and  the  teeth  covered  w^ith 
sordes.  The  abdomen  is  tender  and  distended  and  the  bowels  often 
loose.  The  eruption  is  poorly  developed  and  bluish  in  appearance. 
These  cases  are  usually  fatal,  death  taking  place  within  a  week  or, 
less  commonly,  convalescence  may  occur  after  a  tedious  and  protracted 
illness. 

Such  cases  as  the  above  were  not  rare  during  the  Civil  War.  Camp 
measles  does  not  differ  essentially  from  measles  seen  among  civilians 
save  that  as  a  result  of  privation  and  exposure  the  disease  is  apt  to 
assume  a  more  severe  form.  IMeasles  is  one  of  the  most  formidable  of 
camp  diseases,  as  is  attested  Ky^the  morbi<iitv  and  mortalitv  statistics 
of  the  Civil  War  of  1S61.  Bartholow  says:  "In  one  regiment  which 
came  under  my  observation  every  man  contracted  measles  who  had  not 
had  it  in  early  life."  The  disease  was  much  more  prevalent  in  regiments 
recruited  from  country  districts.  The  mortality  rate  was  high.  In  the 
general  field  hospital  at  Chattanooga  it  was  22. -4  per  cent.,  and  in  the 
tj^iCTST' Hospital  No.  1  at  Nashville  it  was  19.6  per  cent. 

Malignant  Hemorrhagic  Measles. — Black  measles  was,  according 
to  the  descriptions  of  the  older  writers,  much  more  common  years  ago 


500  MEASLES 

than  at  the  present  day.  It  is  also  much  rarer  than  hemorrhagic  small- 
pox, with  which  it  has  certain  features  in  common.  Hemorrhagic 
measles  is  more  apt  to  develop  in  previously  ill  and  debilitated  subjects. 

The  onset  of  the  disease  is  usually  violent,  the  fever  being  high  and 
nervous  symptoms  prominent.  The  eruption  is  bluish  or  purplish  in 
color  and  fails  to  disappear  upon  pressure.  In  other  cases  the  exanthein 
may  appear,  recede  rapidly,  and  be  followed  by  hemorrhagic  extrava- 
sation into  the  skin  in  the  form  of  petechise  or  ecchymOses.  At  the 
'same  time  bloody  discharges  occur  from  various  mucous  merabranes. 
There  is  commonly  severe  epistaxis  and  blood  may  be  observed  in  the 
urine,  stools,  and  vomited  rnatter.  The  patient  becomes  rapidly  ex- 
hausted, the  pulse  is  frequent  and  thready,  the  skin  pale  and  cold,  and 
death  closes  the  scene. 

Trousseau  describes  a  fatal  case  in  a  girl,  aged  five  years,  whom  he 
saw  in  consultation:  "The  fever  had  been  constantly  accompanied  by 
stupor,  which  is  unusual  in  this  disease.  The  eruption  came  out,  but 
the  exanthematous  patches  were  of  a  dark  color,  that  hemorrhagic  hue 
which  does  not  disappear  under  pressure  of  the  finger.  On  the  eighth 
day  slight  delirium  supervened,  and  epistaxis,  which  had  occurred  with 
usual  moderation  during  the  first  period,  became  much  more  profuse. 
.  .  .  .  After  some  hours  other  hemorrhages  developed;  she  had 
hsematuria,  bloody  stools,  and  hsematemesis.  Finally,  within  two  days, 
ecchymotic  spots  appeared  upon  the  back."  The  child  sank  rapidly 
and  died. 

It  must  not  be  supposed  that  all  hemorrhagic  eruptions  in  measles  are 
necessarily  in  malignant  cases.  Attention  has  already  been  called  to 
hsemic  extravasation  into  the  skin  in  attacks  of  average  severity. 

Irregularity  in  the  Origin  and  Spread  of  the  Measles  Exanthem. — 
The  spread  of  the  eruption  of  measles  involving  in  succession  the  face, 
chest,  neck,  abdomen,  arms,  legs,  etc.,  16  a  tolerably  uniform  and 
"diagnostic  phenomenon.  Occasionally  a  departure  from  this  normal 
progression  takes  place.  jXli€-«rupiioiL  rnay^  in  rare  cases,  be  limited 
to  the  face  or  to  the  face  and  trunk.  It  may  begin  oii:the  truiik  or 
"extremities  and  involve  the  face  and  rueck  only  later.  Mayr^  states  that 
the  application  of  irritants  to  the  skin,  such  as  the  use  of  lotions,  oint- 
ments, bandages,  and  compression  from  other  causes  may  determine 
the  point  of  origin  of  the  eruption.  He  is  also  authority  for  the  state- 
ment that  in  paraplegia  from  vertebral  disease  the  rash  is  often  absent 
on  the  paralyzed  lower  extremities. 

Chairou^  reports  a  curious  abnormality  of  the  measles  eruption  which 
occurred  in  a  severe  epidemic  of  measles  at  Rueil  in  1862.  The  eruption 
lacked  intensity,  but  was  accompanied  by  profuse  perspiration  and  a 
vesicular  eruption  similar  to  the  miliary  rash  seen  in  lying-in  women. 
Chairou  proposed  for  this  condition  the  name  of  sweating  measles. 
The  constitutional  symptoms  were  severe  and  uncommon.  The  course 
was  that  of  a  septic  or  typhoid  measles,  with  many  complications  observed 

1  Loc.  cit.,  p.  163. 

2  Essay  awarded  a  prize  by  Academy  of  Medicine  of  Paris  ;  cited  by  Trousseau,  loc.  cit.,  p.  185. 


COMI'IJCATIONH  AND  .S/<:QUf'JLA<J  OF  MI'lAHLKH  501 

in  typlioid  f(!V('r,  siicli  as  periosteal  troul^le  leading  to  necrosis  (*f  the 
ni.'ixillary  hones,  ete.     Tfie  mortality  rate  was  lii^li. 

Recession  of  the  Rash. — \i  occasionally  hapj^ens  that  the  n)(;asle.s 
exantlieni  suddenly  and  prematurely  fades  after  reachinj^  its  maximum 
or  even  l>efore  the  heifjjht  of  the  eruption  is  attained.  The  recession  of 
the  rash  may  l)e  temporary,  tlie  eruption  later  reappearing,  or  it  may 
be  permanent.  The  lay  community  has  a  traditional  dread  of  this 
"striking  in"  of  the  eru})tion,  fearing  the  involvement  of  one  of  the 
internal  organs.  As  a  matter  of  fact  the  sudden  fading  of  the  exanthem 
is  not  tlie  cause,  but  the  result  of  such  condition.  'J^y^.  plienonienon  is 
usually  due  to  severe  pulmonary  involvement,  leadii)g  to  canlijic  fnihire 
"a^nfr'conj^^^  crippling   of   the   circulatory   aftpafafi is.      TIk-    skin 

necomes  pale  and  the  eruption  fades  either  completely  oy  shows  itself 
as  indistinct,  bluish  spots.  With  an  improvement  in  the  heart  action 
the  spots  naturally  acquire  more  color  and  the  eruption,  so  to  speak, 
returns.  Thomas  believes  that  rapid  disappearance  of  the  eruption 
does  not  necessarily  indicate  the  development  of  some  complication. 
He  says:  "I  have  never  had  an  opportunity  to  convince  myself  of  the 
connection  of  a  speedy  fading  of  the  spots  with  the  sudden  occurrence 
of  a  complication.  A  simple  rapidly  progressing  paleness  of  these  can 
certainly  not  be  considered  anomalous." 

Postrubeolic  Eruptions. — Reference  has  already  been  made  to  the 
occurrence  of  a  morbilliform  rash,  associated  at  times  with  renewed  fever, 
developing  after  convalescence  from  measles.  In  rare  cases  other 
eruptions  may  make  their  appearance  about  this  time.  Roger^  has 
seen  cases,  both  of  recurrent  measles  and  also  accidental  erythematous 
rashes  after  measles.  He  reports  an  instance  of  the  latter  in  a  young 
woman  twelve  days  after  an  attack  of  measles,  and  another  in  an  infant, 
two  and  one-half  months  old,  thirty-eight  days  afterward. 

Meyer-Hoffmeister^  saw  a  scarlatiniform  erythema  during  con- 
valescence from  measles. 

COMPLICATIONS  AND  SEQUEL  .X  OF  MEASLES. 

Larynx. — A  moderate  grade  of  catarrhal  laryngitis  is  uniformly 
present  in  measles,  and  is,  therefore,  scarcely  to  be  regarded  as  a  com- 
plication. The  laryngeal  symptoms  develop  early  in  the  invasive  stage, 
giving  rise  to  hoarseness,  frequent  cough,  arid  occasionally  spasmodic 
dyspnpea*  The  cough  is  dry,  loud  and  hollow  in  tone,  and  in  the  begin- 
ning unproductive  of  expectoration.  The  paroxysms  of  coughing  are 
often  violent  and  incessant,  seriously  interfering  with  sleep.  I'pon  the 
appearance  of  the  cutaneous  eruption  the  cough  becomes  looser  and 
less  frequent  and  is  accompanied  by  expectoration.  Holt  states  that 
severe  catarrhal  laryngitis  is  present  in  about  10  per  cent,  of  all  cases 
of  measles. 

Ulcerative  Laryngitis. — Ulcerative  laryngitis  occurs  in  a  certain  pro- 
portion of  severe  cases.    In  such  instances  the  inflammation  is  so  intense 

1  Loc.  cit.,  p.  875.  2  Quoted  by  Thomas,  loc.  cit.,  p.  90. 


502  MEASLES 

as  to  lead  to  necrosis  of  the  mucous  and  submucous  tissues.  The  vocal 
cords  are  commonly  involved  in  the  destructive  process.  Barthez  and 
Rilliet  found  ulcerations  and  erosions  in  almost  one-half  of  the  cases 
of  measles  that  came  to  autopsy.  Pseudomembranous  deposits  were 
present  in  about  one-fifth  of  the  cases. 

Gerhardt^  has  seen  these  ulcerations  by  laryngoscopic  examination 
during  life.  He  has  found  them  particularly  upon  the  posterior  wall 
of  the  larynx  in  cases  that  exhibit  marked  stenosis.  They  may  be  seen 
at  times  early,  but  are  more  commonly  observed  during  the  eruptive 
stage.  The  superficial  ulcerations  give  rise  to  a  rough,  dry,  frequently 
repeated  cough,  accompanied  by  spasmodic  attacks.  There  is  pain  upon 
coughing,  speaking,  or  swallowing,  and  often  considerable  dyspnoea. 

The  most  dangerous  form  of  laryngitis  is  that  accompanied  by  the 
formation  of  a  pseudomembrane,  the  so-called  membranous  laryngitis. 
The  fatality  of  this  complication  is  frightful.  In  the  Hospice  des  Enfants 
Assistes  in  Paris,  Granlou^  found  this  complication  235  times  among 
1633  cases  of  measles;  out  of  these  235  patients  218  died,  a  most  appalling 
mortality. 

We  have  seen  a  number  of  these  cases  that  had  to  be  intubated;  they 
all  succumbed  to  the  disease.  Holt  has  collected  35  cases  of  membranous 
laryngitis  out  of  2837  cases  of  measles  from  miscellaneous  sources;  he 
remarks  that  this  complication  is  more  frequent  than  this  in  institution 
epidemics. 

^^^^{Terpbranowg.  Uryngitis  JOjay  resiult  from  the  action  of  Jhestrepto;;;^ 
coccus,  the  diphtheria  bacillus,  and,  perhaps,  other  organisms.  ^Holt 
states  that  when  the  membrane  forms  in  the  larynx  at  the  height  of , the 
disease  it  is  almost  always,  of,  streptococcic  origin;  when  it  develops  at*- 
a  later  period  it  is  usually  due  to  the  Klebs-Loeffler  organism. ,,,  The 
.majority  of  cases  appear  to  be  due  to  pyogenic  bacteria.  The  false 
membrane  is  not  always  limited  to  the  larynx,  but  may  invade  the  fauces, 
nose,  and  mouth.  The  laryngeal  stenosis  usually  comes  on  gradually, 
although  more  commonly  the  symptoms  may  be  sudden  in  their  appear- 
ance. 

The  dyspnoea  frequently  becomes  so  alarming  as  to  necessitate 
intubation  or  tracheotomy.  These  procedures,  however,  give,  as  a  rule, 
but  temporary  relief,  for  a  fatal  bronchopneumonia  is  almost  sure  to 
develop.  «.^..«--- 

The  diagnosis  between  true  laryngeal  diphtheria  and  membranous 
laryngitis  of  streptococcus  origin  can  only  be  indubitably  settled  by  a 
bacteriological  examination;  the  former  condition  is  apt  to  develop  late 
and  the  latter  at  the  height  of  the  disease.  The  prognosis  appears  to 
be  equally  desperate  in  both  conditions. 

Lungs. — The  trachea  and  larger  bronchial  tubes  are  so  commonly 
involved  in  the  catarrhal  process  in  measles  that  a  moderate  grade  of 
tracheitis  and  bronchitis  may  be  regarded  as  belonging  to  the  normal 
symptomatology  of  the  disease.     It  is  only  when  the  inflammatory 

1  Lehrbuch  der  Kinderkrankheiteu,  p.  63. 

-  La  rougeole  h  rh6spice  des  enfants  assist6s,  Paris,  189a. 


C.OMI'hldATIONH  AND  ^ICljU Ef.M  01''  Mf'JASL/'JS 


503 


disturbance  is  intense,  ;ui(l  downward  extension  takes  ]:)lace  that  the 
complication  assunies  a  sei'ious  Jisjx'c-I.  Severe  hroneliiiiJ  eatarrfi  usually 
niMiiifests  ilseU'  just  at  or  after  tin;  lieiirhi  of  iIk;  eruptive  statfe;  if  it  )>e 
sudieienlly  widespread,  llie  fever,  wliicli  at  this  time  falls,  will  eoutinue 
to  remain  elevated.  There  is  fre(|uent  eouf^hin^,  accompanied  hy  muco- 
purulent exj)ect()ration. 

Foreifi;!!  writers  still  employ  the  term  (•(lylllary  hr one} litis;  the  tendency 
in  this  country  is  to  look  upon  the  involvement  of  the  minute  bronchioles 
as  an  essential  part  of  a  bronchopneumonia.  The  symptoms  of  capil- 
lary bronchitis,  therefore,  are  virtually  those  of  catarrhal  pneumonia. 


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Measles.  Pneumonia. 

Boy,  five  years  old.  (Tuley.) 


Bronchopneumonia. — Bronchopneumonia  is  the  most  common  and 
most  fatal  of  all  of  the  complications  of  measles.  Other  conditions  fade 
into  insignificance  when  compared,  to  the  slaughter  tliat  this  complica- 
tteiToccasions.  Over  a  half-century  ago  Gregory  wrote:  "I  am  sure  I 
^peaK  much  within  bounds  when  I  say  that  nine-tenths  of  the  deaths 
by  measles  occur  in  consequence  of  pneumonia." 
*^Bartels  met  with  68  cases  of  bronchopneumonia  among  573  cases  of 
measles,  or  11.9  per  cent.;  Ziemssen  and  Krabler  report  50  attacks  of 
pneumonia  among  311  cases  of  measles,  or  16.1  per  cent.  The  figures 
of  Embden  give  a  much  smaller  incidence — 27  attacks  in  461  cases,  or 
5.9  per  cent.  The  frequency  of  this  complication  seems  to  vary  con- 
siderably in  different  epidemics.  It  is  much  more  common  in  foundling 
■^sylums,  orphanages,  and  similar  institutions.  It  is  more  apt  to  attack 
feeBlelind  poorly  nourished  children  and  those  debilitated  by  previous 
illness.     This  complication   is  particularly  prone   to   attack  children 


504  MEASLES 

under  two  years  of  age.  Holt  states  that  in  two  epidemics  in  the  Nursery 
and  Child's  Hospital,  embracing  about  300  cases,  nearly  all  in  children 
under  three  years  old,  bronchopneumonia  occurred  in  about  40  per  cent, 
of  the  cases.  Of  those  who  had  pneumonia,  70  per  cent.  died.  Henoch 
says  that  a  certain  amount  of  pneumonia  is  seen  in  nearly  all  fatal 
cases  01  measles. 

Bronchopneumonia  usually  manifests  itself  when  the  eruption  begins 
to  decline,  although  the  onset  may  be  delayed  to  a  later  period.  The 
posteruptive  decline  in  the  temperature  fails  to  occur,  the  fever  instead 
remaining  in  the  neighborhood  of  103°  F.,  with,  perhaps,  morning  remis- 
sions of  a  degree  or  so.  The  pulse  is  greatly  increased  in  frequency, 
and  the  respiration  is  shallow  and  hurried,  and  not  infrequently  labored 
and  difficult;  it  is  a  pitiful  sight  to  see  the  little  patient  with  dilating 
nostrils  and  a  livid  countenance  raise  itself  in  the  bed  to  relieve  its 
distressed  breathing.  The  cough  may  be  short  and  repeated  or  infrequent 
and  spasmodic.  In  unfavorable  cases  there  is  protracted  fever,  progress- 
ive increase  in  the  rapidity  of  respiration  (60  to  80),  cold  extremities, 
extreme  weakness,  and  rapid-running  pulse.  Nourishment  is  refused 
and,  when  taken,  is  often  vomited.  Great  pallor  develops  and  toward 
the  end  a  characteristic  lividity  is  seen.  A  few  hours  before  death  the 
temperature  may  rise  to  great  height,  107°  or  108°  F.  In  favorable  cases 
the  temperature  at  the  end  of  ten  days  or  two  weeks  declines  gradually 
to  normal,  the  cough  lessens,  the  respiration  improves,  the  child  becomes 
brighter,  desires  more  food,  and  takes  an  increasing  interest  in  its 
surroundings. 

The  symptoms  that  indicate  the  presence  of  a  bronchopneumonia 
are  protracted  fever^  cough,  rapid  pulse,  hurried  aiid  labored  breathing, 
and  prostration.  Percussion  will  often  discover  some  dulness  over  one 
or  both  of  the  lower  lobes  posteriorly;  the  respiratory  murmur  is 
diminished  and  bronchovesicular  breathing  is  heard;  in  addition  to 
the  coarse  rales  heard  in  the  larger  tubes,  fine,  moist  rales  are  audible 
over  the  small,  consolidated  areas. 

Lobar  Pneumonia. — Isobar  or  croupous  pneumonia  is  a  much  less 
frequent  complication  of  measles  than  the  catarrhal  form,  and  is  apt, 
when  it  occurs,  to  develop  in  older  patients.  This  form  of  pneumonia 
is  characterized  by  higher  fever  with  fewer  remissions,  by  its  limitation 
to  one  lung  or  lobe  thereof,  by  the  presence  of  pleuritic  pains,  a  shorter 
course  terminated  by  crisis,  and  a  lower  mortality  rate. 

Pleurisy. — Pleurisy    with    effusion    is    an    unusual    complication    of 
measles.     In  some  epidemics  it  may  develop  secondarily  to  a  sevejgL^ 
pneumonia7  in' which  case  it  is  apt  to  eventuate  in  an  empyema.- '^^ 

Fiirbringer^  calls  attention  to  the  occasional  occurrence  of  a  primary 
pleurisy  with  effusion.  He  has  observed  a  number  of  cases,  most  of 
which  ran  an  acute  course  and  were  probably  purulent  from  the  begin- 
ning. 

Pulmonary  Tuberculosis. — Pulmonary  tuberculosis  may  manifest  itself 
as  a  termination  of  a  long-standing  bronchopneumonia  occurring  after 

*  Eulenberg's  Real-Encyclopedia,  vol.  xii.,  second  edition,  p.  559;  quoted  by  von  Jilrgensea. 


COMPJACATIONH  AND  S/'JQf/l'Jf.A'J  Oh'  MHASLHH  505 

measles.  Tlie  l)r()ncliial  catarrli  and  llie  l(;won-(l  nisisfarioe  of  the 
patient  render  the  iniphintation  of  tuhfa-ciilosis  n'.-ulily  fxpHc^able.  Jr]_ 
rases  in  wliicli  a  Ijifciit  glaiuhilar  tuherculosis,  particularly  of  the 
ihonicic  lymph  nodes,  li;i,s  existed,  the  "attack  of  measles  stiniuTafeslHe 
j)revioiis  disense  to  noxious  activity.  Tn  some  cases  tuberculosis  rnay 
""develop  as  a  direct  se((uel  of  measles,  an  irregular  temperature  persisting 
after  the  incomplete  convalescence  from  the  latter  disease.  The  tuber- 
culous disease  may  take  the  form  of  an  acute  miliary  tuberculosis. 
Holt  truly  says:  "An  attack  of  measles  in  a  child  vv^ith  tuberculous  ante-  ^ 
cedents  should  always  be  looked  upon  with  a])prehension." 

Barthez  and  Rilliet  have  observed  gmrjreji/;  of  the  Inn.r/s  in  four 
instances,  and  Steiner  and  Neureutter  have  mcl  wiih  this  complication 
in  two  patients.  This  much  to  be  dreaded  condition  may  have  its 
origin  in  a  severe  bronchopneumonia. 

Alimentary  Tract.- — From  what  has  already  been  said  concerning  the 
measles  exanthem  it  is  evident  that  a  mild  inflammation  of  the  buccal 
and  pharyngeal  mucous  membrane  is  uniformly  observed.  This  comes 
on  in  the  invasive  stage  and  tends  to  subside  as  the  cutaneous  eruption 
increases  in  development. 

The  cheeks,  gums,  tongue,  soft  palate,  tonsils,  and  pharyngeal  wall 
all  participate  in  the  catarrhal  process.  In  feeble  and  debilitated 
children  this  inflammation,  especially  under  the  influence  of  infection 
with  pyogenic  and  other  bacteria,  may  lead  to  complications  which 
are  not  only  subjectively  distressing,  but  of  serious  import.  Aphthous 
stomatitis  has  been  reported  by  a  number  of  writers.  The  sores  may 
give  rise  to  much  pain  and  interfere  with  the  desire  of  the  child  to  take 
nourishment.  Ulcerative  stomatitis  not  infrequently  develops,  particu- 
larly in  the  buccogingival  furrow.  This  is  characterized  by  the  form- 
ation of  small  patches  covered  with  grayish,  necrotic  epithelium.  When 
the  dead  epithelial  covering  is  cast  off  there  are  disclosed  to  view  ulcer- 
ations of  varying  depth,  with  sharp  and  irregular  edges;  the  base  is 
frequently  covered  with  a  pseudomembranous  deposit.  These  losses 
of  tissue  are  not  infrequently  seen  on  the  gums,  and  about  the  lips,  par- 
ticularly the  oral  commissures ;  in  the  latter  regions  each  movement  of  the 
mouth  causes  pain  and  induces  bleeding.  In  poorly  nourished  children 
these  ulcerations  may  last  for  a  long  time  before  complete  healing 
occurs. 

A  fortunately  rare  but  most  frightful  complication  of  measles  is  that      > 
form  of  gangrene  variously  designated  cancrum  oris,  gangrenous  stom-   ^ 
otitis,  or  noma.     The  fatal  character  of  this  complication  makes  the    ^"^-^ 
condition  of  sufficient  importance  to  warrant  a  description  elsewhere. 
To  be  sure,  there  are  less  serious  forms  of  gangrenous  stomatitis  in 
which  the  loss  of  tissue  is  circumscribed.     We  have  not  infrequently 
seen  necrosis  of  a  portion  of  the  gum  and  subjacent  alveolar  process 
which,  after  the  throwing  off  of  the  slough,  has  been  followed  by  thorough 
healing;  in  some  of  these  cases  a  portion  of  the  bone  and  the  neighboring 
teeth  have  come  away. 

In  a  certain  proportion  of  cases  membranous  patches  may  be  seen 


506  MEASLES 

on  the  tonsils  and  neighboring  palatal  mucous  membrane.  This 
process  may  spread  downward  into  the  larynx  and  give  rise  to  the 
dreaded  membranous  laryngitis.  The  pseudomembrane  may  be  of 
streptococcic  or  staphylococcic  origin  like  the  exudate  seen  in  scarlatina, 
or  it  may  be  true  diphtheria.  In  some  cases  tonsillitis  is  observed,  in 
which  event  there  is  enlargement  and  congestion  of  these  structures  and 
pain  upon  swallowing. 

The  stomach  is  but  rarely  the  seat  of  any  serious  complication. 

Diarrhoea. — ^piarrhoea_is  a  common  and  not  infrequently  a  serious 
accompaniment  of  measles.  It  may  exist  in  all  grades,  from  a  slight 
catarrhal  enteritis,  lasting  but  a  few  days,  to  a  severe  enterocolitis 
with  fatal  outcome.  x4ls  would  naturally  be  expected,  diarrhoea  is  more 
jcommon  in  the  summer  months  and  especially  in  extremely  hot  summers. 
This  complication  is  also  more  frequently  observed  in  tropical  and  sub- 
tropical countries.  Gregory  says:  "In  India  and  other  hot  countries 
thoracic  complications  are  rare;  diarrhoea  and  dysentery  prove  the 
usual  and  most  troublesome  sequelae."  It  is  not  at  all  uncommon  for  a 
mild  diarrhoea  to  be  present  in  the  invasive  and  early  eruptive  stages. 
There  are  frequent  loose  and  watery  movements,  with  or  without  pain, 
which  tend  to  subside  as  the  eruptive  stage  advances.  The  severe 
forms  of  enteritis  and  ileocolitis  usually  develop  late  during  the  decline 
of  the  eruption.  In  some  cases  the  large  intestine  is  involved  and 
symptoms  of  dysentery  manifest  themselves;  pain  and  tenesmus  are 
present  and  frequent;  small,  bloody  stools  containing  mucus  are  passed. 

Diarrhoea  appears  to  be  more  common  in  some  epidemics  than  in 
others.  Willischanin^  observed  an  epidemic  of  measles  in  a  girls'  school 
in  which  10  out  of  50  of  the  patients  had  diarrhoea  during  convalescence. 
It  lasted  from  three  to  five  days  and  was  believed  to  be  due  to  the 
elimination  of  special  toxins. 

Intestinal  inflammation  is  most  frequently  observed  in  infants  and 
young  children,  in  whom  it  not  infrequently  leads  to  a  fatal  termination. 
Cases  are  on  record,  however,  in  which  adults  have  succumbed  to 
measles  as  a  result  of  this  complication. 

Nervous  System. — As  is  the  case  with  most  infectious  diseases,  measles 
may  be  accompanied  or  followed  by  a  great  variety  of  disturbances  due 
to  involvement  of  the  brain,  spinal  cord,  or  the  peripheral  nerves.  When 
the  fact  is  recognized  that  measles  attacks  almost  the  entire  human 
family,  the  relative  infrequency  of  nervous  complications  may  be 
appreciated. 

Mental  Disorder. — Measles  is,  in  rare  instances,  followed  by  insanity, 
which  usually  takes  either  the  form  of  mania  or  dementia.  Christian^ 
reports  a  case  of  temporary  mania  and  paralysis.  Finkelstein^  saw  2 
cases  of  mania  after  measles,  and  Bond^  observed  a  case  developing  on 
the  eighth  day  of  the  disease.  Weber  noted  delusions  of  persecution  in 
one  of  his  patients.    In  an  epidemic  of  108  cases  occurring  in  an  insti- 

,  1  St.  Petersburger  med.  Wochen.,  December  4, 1893  ;  quoted  by  Williams,  loc.  cit. 
2  Centralbl.,  1874,  p.  95.  »  Vratsch,  1898,  No.  20. 

■*  Maryland  Medical  Journal,  January  29,  1898. 


COMPIJdATIONS  AND  S/<;(J(/ l'J/..^<J  Oh'  MEASLHS  ,007 

tution  ill  Vir^iniii  iiiid  iTporlcd  hy  Siiiitli  ;i,ii(l  l);il)iK-y,  iiisiinily  eiiflinjf 
in  recovery  <level()|)e<l  in  iliree  pidieiits. 

Beach'  analy/cd  20()()  ciises  of  idiocy  iind  found  'M  d.'So  per  cent.) 
which  could  he  traced  to  attacks  of  infectious  diseases;  of  this  niirnljer 
11  were  attributed  to  attacks  of  measles.  Nearly  all  the  cases,  however, 
were  in  persons  with  neurotic  antecedents. 

Cerebral  and  Spinal  Paralysis.  I*; i rid ysis  followirif^  measles  is  a  rare 
complication.  AUyn^  was  able  to  collect  hut  41  instances,  'A')  of  which 
were  palsies  of  cerebral  origin.  The  onset  of  the  complication  is  abrupt, 
and  commonly,  though  not  always,  marked  by  convulsions.  In  other 
cases  somnolence  or  coma  occurs  in  the  beginning.  P'ollowing  upon 
the  convulsions  or  coma  the  evidences  of  paralysis  are  observed.  In 
spinal  paralysis  coma  and  convulsions  are  absent.  The  paralyses, 
according  to  Allyn,  usually  appear  during  convalescence  and  most 
frequently  from  the  latter  part  of  the  first  to  the  close  of  the  third  week 
after  the  onset  of  the  attack.  Of  21  reported  cases,  11  developed  palsy 
between  the  fifth  and  sixteenth  day,  while  5  more  prol)ably  belong  to 
this  period,  although  the  data  are  imperfect.  In  the  remaining  cases 
3  developed  convulsions  on  the  second  day  of  the  eruption,  1  a  month 
after  the  onset  of  the  measles,  and  1  in  from  five  to  six  weeks.  The 
prognosis  as  to  life  is  good.  In  only  4  of  the  cases  did  a  fatal  result 
ensue.  In  some  of  the  cases  the  lesions  were  more  or  less  permanent, 
aphasia  and  muscular  atrophy  persisting  some  years  after  the  attack. 
The  paralyses  collated  by  Allyn  were  chiefly  cerebral  palsies  of  the 
hemiplegic  type,  but  included  also  disseminated  myelitis  and  ascending 
spinal  palsy. 

Cases  of  paralysis  have  since  been  reported  by  a  number  of  authors. 
Dawson  Williams^  saw  a  case  of  disseminated  sclerosis  in  a  girl  three 
and  a  half  years  old  on  the  fourth  day  of  an  attack  of  measles. 

Bruce  records  a  case  of  diffuse  myelitis  and  Barlow  an  extensive 
softening  of  the  cord.  Ormerod  observed  paralytic  symptoms  one 
month  after  measles  in  three  children.  Andeoud  and  Jaccard^  report 
a  case  of  vesical  paralysis  in  a  nine-year-old  girl,  and  Ortholon^  a  true 
paraplegia  in  a  three-year-old  girl. 

Paralysis  after  measles  has  also  been  reported  by  Graf,"  ]Morton,'  and 
Ellison,*^  who  observed  a  case  of  acute  ascending  myelitis. 

False  Disseminated  Sclerosis.- -There  occasionally  occurs  in  measles, 
as  in  smallpox  and  other  infectious  diseases,  sudden  unconsciousness 
followed  by  loss  of  power  of  speech  and  certain  other  paretic  and  ataxic 
symptoms.  This  may  occur  during  the  febrile  stage  or  during  con- 
valescence. Rapid  recovery  may  ensue  or  a  train  of  symptoms  may 
develop  suggesting  disseminated  sclerosis.  Instead  of  the  condition 
being  progressive  there  is  a  distinct  tendency  to  improve. 

1  British  Medical  Journal,  1895,  vol.  ii.  p.  707.  -  Medical  News,  NoTcmber  28, 1S91. 

3  Med.-Chir.  Soc,  November  28,  1893.  *  Rev.  m.5d.  de  la  Suisse  romande,  1894. 

6  Tli^se  de  Bordeaux,  November  23,  1894. 

•  Indiana  Medical  Journal,  1892  and  1893,  p.  176. 

'  Archives  of  Pediatrics,  1897,  vol.  xiv.  pp.  541-544.  8  Lancet,  1896,  vol.  ii.  p.  1077. 


508  MEASLES 

Barthez  and  Sanne  have  collected  a  series  of  8  cases  characterized 
by  paresis  of  the  soft  palate,  pharynx,  tongue,  and  muscles  of  the  neck. 
In  4  cases  the  symptoms  appeared  early  in  the  course  of  measles,  and 
in  the  remaining  4  at  the  end  of  three  weeks.  Recovery  took  place  in 
all  of  the  cases,  in  from  three  to  twenty  days. 

Meningitis. — Instances  of  inflammation  of  the  membranes  of  the  brain 
have  been  reported  by  Spiess,  Voit,  Meyer-Hoffmeister,  Kellner, 
Constant,  Loschner,  Thore,  Bufalini,  King,  Mettenheimer,  and  Harvey.^ 
Frank,  Rilliet,  and  Starck  have  observed  spinal  meningitis  after 
measles. 

Chorea. — ^Chorea  is  an  occasional  sequel  of  measles.  Cases  have  been 
recorded  by  Sibergundi,  Boning,  and  others.  In  an  analysis  of  439  cases 
of  chorea  made  by  Stephen  MacKenzie  for  the  Collective  Investigation 
Committee  of  the  British  Medical  Association,  measles  or  measles  and 
anaemia  were  found  to  be  the  sole  antecedent  illnesses  in  49  cases — 
nearly  9  per  cent.  Barthez  and  Rilliet  have  noted  after  measles  a 
prompt  recovery  from  a  chorea  of  some  months'  duration. 

Skin. — Mention  has  already  been  made  of  the  accidental  erythem- 
atous rashes  which  may,  in  rare  cases,  precede  or  follow  the  true 
exanthem  of  measles. 

During  the  invasive  period  it  is  not  rare  for  herpes  facialis  to  appear, 
a  phenomenon  which  develops  in  many  infectious  processes.  Urticaria 
may  also  occur  either  in  the  course  of  the  disease  or  at  a  later  period. 
The  urticarial  eruption  is  usually  moderate  and  of  short  duration. 
Claus^  reports  urticaria  occurring  in  two  cases  of  measles  during  the 
period  of  incubation. 

Several  authors  have  called  attention  to  the  development  of  a  bullous 
eruption  resembling  pemphigus.  Cases  have  been  reported  by  Krieg,^ 
Loschner,  Henoch,*  Steiner,^  Du  Castel,^  and  recently  by  Baginsky.'^ 
Steiner  saw  4  cases,  all  in  the  same  family.  The  blebs  varied  in  size 
from  a  pea  to  a  pigeon's  egg,  came  out  in  crops,  attacked  both  the  skin 
and  mucous  membranes,  were  accompanied  by  fever,  and  occurred  at 
any  time  during  the  course  of  the  disease,  before,  during,  or  after  the 
measles  exanthem. 

In  Henoch's^  patient  the  bullae  were  so  large  that  a  single  one  covered 
each  cheek;  2  out  of  these  5  cases  terminated  fatally.  Masarei^  saw 
upon  the  palms  and  soles  during  desquamation  large  blebs  which  burst 
and  left  obstinate  and  painful  ulcers. 

Gangrene  may  attack  other  parts  of  the  skin  than  the  cheek  and 
genitalia,  which  are  the  most  common  sites  of  the  process.  Thomas, 
of  Paris,  has  reported  an  extensive  gangrene  of  the  buttocks  in  a  child 

1  Journal  of  the  American  Medical  Association,  1897,  vol.  xxix.  pp.  1149-1161.    The  other  authors 
mentioned  are  quoted  by  Thomas. 
'  Jahrbuch  f.  Kinderh.  u.  Phys.  Erzieh.,  June,  1894. 
3  Cst.  Jahrbuch,  1843,  p.  219.  *  Berlin,  klin.  Wochenschrift,  1882,  p.  193. 

6  Jahrbuch  f.  Kinderh.,  new  series,  vol.  vii.  p.  346. 

«  Rev.  g6n.  de  clin.  et  de  th^rap.,  Paris,  1897,  vol.  xi.  p.  609. 

7  Archiv  f.  Kinderh.,  1900,  Bd.  xxviii.,  H.  1  and  11. 

8  Mentioned  by  von  Jtirgensen,  loc.  cit.,  p.  300.  ^  Quoted  by  Thomas. 


COMPLICATIONS  AND  SI<JQ(J I'JL/l'J  OF  Mh'ASLI'JS  509 

two  years  of  afre.  Mayr,  Fayc,  liidternvy,  and  CaiToll'  )(|>(;rt  instances 
of  jraiifrreiie  attackinf>;  various  portions  of  the  eutaneons  snrfa(;e. 

l7npelir/o,  boils,  and  abscesses  are  occasionally  observed  duririf^  con- 
valescence from  measles.  They  represent  varying  grades  of  infection 
witii  tlie  common  pyogenic  organisms.  Kczema  occasionally  makes  its 
initial  ap})earance  after  an  attack  of  measles  and  may  persist  for  an 
indefinite  period.  On  the  other  hand,  chronic  eczemas  have  been 
known  to  disappear  after  an  attack,  as  in  cases  reported  by  Behrend 
and  others.  Psoriasis  has  been  observed  to  appear  for  the  first  time 
after  measles.  Measles,  of  course,  does  not  cause  the  ])soriasis,  but 
merely  determines  the  date  of  its  outbreak. 

Disseminated  tuberculosis  of  the  skin  may  follow  in  the  wake  of 
measles,  as  in  the  cases  reported  by  Du  Clastel,^  Haushalter,''  and 
Adamson.'' 

Du  Castel  saw  3  cases  and  remarks  that  "it  is  not  exceptional  to  see 
a  disseminated  tuberculosis  of  the  skin  as  a  sequel  to  measles."  This 
usually  attacks  the  face,  legs,  and  especially  the  upper  extremities.  The 
lesions  appear  soon  after  the  decline  of  the  measles  eruption  in  the 
form  of  small,  deep-red  nodules.  Haushalter  saw  2  cases  of  scrofulous 
lichen,  1  of  which  later  developed  enlarged  glands  and  tuVjerculous 
gummata.  Adamson's  case  was  one  of  multiple  warty  lupus  occurring 
on  the  arms  and  legs.  The  patient  subsequently  developed  a  post- 
pharyngeal abscess  and  later  hip  disease. 

Roger'^  observed,  in  the  spring  of  1900,  4  cases  of  erythema  nodosum 
after  attacks  of  measles.  A  girl,  aged  seventeen  years,  eleven  days  after 
the  termination  of  an  attack  of  measles  of  moderate  intensity,  developed 
fever,  and  twenty-four  hours  later  a  typical  erythema  nodosum  of  the 
legs  and  subsequently  the  arms,  accompanied  by  painful  joints;  the 
condition  lasted  fifteen  days. 

The  other  3  cases  were  analogous;  they  occurred  in  patients  fifteen, 
seventeen,  and  twenty-six  years  of  age,  respectively.  Fever  appeared 
from  nine  to  ten  days  after  the  termination  of  measles.  The  erythem- 
atous nodes  and  the  joint  involvement  persisted  from  seven  to  ten  days. 

Eyes. — Ocular  complications  are  not  rare  in  measles,  a  fact  which 
is  easily  explained  by  the  severe  catarrhal  involvement  of  the  conjunctiva 
during  the  invasive  and  eruptive  stages.  The  eyes  are  particularly  apt 
to  suffer  in  scrofulous  children.  Corneal  ulcerations  mav  occur,  and, 
in  bad  cases,  lead  to  perforation  and  general  panophthalmitis.  It  is  not 
rarejfor  obstinate  blepharitis,  granular  lids,  or  keratitis  to  persist  a  long 
Time  after  convalescence  from  the  original  disease.  Comby  states  that 
proper  Carre  of  the  eyes  gTeatly  reduces  the  number  of  ocular  complica- 
tions, and  in  support  thereof  mentions  the  fact  that  he  observed  only 
17  cases  of  conjunctivitis  of  moderate  intensity  among  71.5  cases  of 
measles. 

1  Quoted  by  Thomas. 

-  Annal.  de  derm.,  etc.,  1898,  tome  ix.,  Nos.  8  and  9,  p.  729.  •'  Ibid.,  No.  5,  p.  455. 

•1  British  Journal  of  Dermatology,  1899,  p.  20. 

s  Loc.  cit.  p.  875. 


510  MEASLES 

Ears. — ^Inflaimnation  of  the  middle  ear  is  by  ilo -^Hieaiis.,arLJ4iicommon 
complication  of  measles,  although  it  does  not  develop  as  frequently  as 
in  scarlatina.  The  catarrhal  inflammation  of  the  nasal  passages  fre- 
quently extends  along  the  Eustachian  tubes  to  the  middle  ear.  Bezold^ 
carefully  explored  the  ears  in  16  fatal  cases  of  measles,  in  all  of  which 
he  found  inflammatory  changes.  The  tympanic  cavity  contained  either 
a  mucopurulent  exudation  or  a  material  that  was  frankly  puriform. 
The  streptococcus  pyogenes  was  present  in  about  50  per  cent,  of  the 
cases;  in  the  other  half  the  staphylococcus  aureus  and  albus  were  found. 
The  raucous  membrane  is  red,  swollen,  and  covered  with  a  muco- 
purulent or  seropurulent  exudate.  Tobietz^  examined  the  ears  of  22 
cases  of  measles  at  autopsy  and  confirmed  the  above-mentioned  find- 
ings. 

Both  ofjl^ese  writers  are  in  accord  as  to  the  early  development jqJE, the 

aural  catarrh.    The  ear  troul)le  is  hot  regarded  as  due  to  a  secondary 

"infection,  but  is  rather  the  result  of  the  localization  in  this  region  of 

"the  enanthe^3^  j^^^^  otitis  may  therefore  develop  in  the  early 

eruptive  period.     In  a  case  studied  by  Tobietz  that  died  twenty-four 

hours  after  the  appearance  of  the  eruption,  otitis  was  already  present. 

This  early  otitis  is  comparatively  mild  and  usually  does  not  lead  to 
perforation  of  the  tympanic  membrane.  The  later-developing  otitis 
media  usually  results  from  infection  from  the  nasopharynx,  and  is  much 
nibre  prone  to  end  in  suppuration  and  perforation. 

Severe  purulent  otitis  media  appears  to  be  more  common  in  some 
epidemics  of  measles  than  in  others.  Downie''  states  that  children  who 
have  adenoid  vegetations  and  suffer  from  catarrh  of  the  throat  and  nose 
are  more  apt  to  develop  middle-ear  trouble.  He  furthermore  claims  that 
the  horizontal  posture  of  the  sick  child  favors  Eustachian  infection  and 
retention  of  the  inflammatory  products  within  the  middle  ear.  Of  501 
cases  of  tympanic  involvement  in  children  seen  by  Downie,  the  con- 
dition was  attributable  to  measles  in  131  instances,  or  26.1  per  cent. 
Curiously,  only  63  cases  (12.6  per  cent.)  were  observed  that  developed 
during  an  attack  of  scarlet  fever. 

It  is  not  always  easy  to  diagnose  the  onset  of  an  otitis  media,  particu- 
larly in  young  children  who  are  unable  to  make  verbal  complaint.  ^  The^ 
complication  most  commonly  develops  about  the  end  of  the  second 
week.  Children  are  cross  and  fretful,  frequently  toss  the  head  and 
cry  out  with  pain.  The  temperature  is  usually  elevated  and  may  rise 
to  great  height.  When  an  otherwise  inexplicable  rise  of  temperature 
occurs  about  this,  time,  the  "possibility  of  purulent  otitis  must  be  con- 
-Jfdered.  Inspection  of  the  tympanic  membrane  is  not  an  easy  task  in 
young  children.  When  this  can  be  accomplished  the  membrane  is  seen 
to  be  congested  and  lustreless,  and  when  pus  is  present  the  tympanum 
bulges  into  the  meatus,  the  puriform  secretion  shining  through  the 
lower  tympanic  segment. 

In  severe  cases  of  middle-ear  disease  necrosis  of  the  ossicles  or  of  the 

1  MiiQchener  med.  Wochenschrift,  March,  1896.  2  Quoted  by  Comby,  loc.  cit. 

8  British  Medical  Journal,  1894,  vol.  ii.  p.  1163. 


COMPLICATIONS  AND  HI'Kid KL/K  OF  M/'JASIJ'JS  F)]] 

surl-oundiiifij  bony  walls  uiuy  take  place.  Huikner'  says:  "An  invasion 
of  the  labyrinth  by  cocci  causing  necrosis  has  been  repeatedly  dernon- 
strated  of  late.  The  lesion  results  in  a  very  serious  loss  of  functional 
power."  The  suj)|)urative  inflaniination  may  extend  to  the  mastoid 
cells  or,  in  rare  (•iis(\s,  to  the  membranes  of  the  brain.  Ashby  arifl 
Wriglit  have  pointed  out  the  fact  thnt  infection  may  take  j>lace  througli 
the  petromastoid  suture,  which  in  infancy  is  still  ununited.  Purulent 
meningitis,  abscess  of  the  brain,  or  thrombosis  of  the  lateral  sinus  might 
thus  (levelop.  In  general  it  may  be  stated  that  mi(Jdle-ear  troul)le 
complicating  measles  is^less  serious  than  that  whicli  occurs  in  scarlet 
fever. 

"  I\l;iny  ciiscs  of  (Icaf-miiHsm  are  traceable  to  attacks  of  measles.  Kerr, 
Love,  and  Addison^  have  collected  statistics  from  ihstitutions  in  Great 
Britain  which  show  that  of  1140  deaf-mutes,  138,  or  9.8 ^per^  cent., 
attributed  their  lo.ss  of  hearingTo^-ttaCks  of  "measles.  "O'f'lCTS  accjufrerl 
cases  in  American  institutions,  52,  or  3.1  per  cent.,  were  due  to  measles. 
Among  1989  acquired  cases  on  the  continent  of  Europe,  84  cases,  or 
4.2  per  cent.,  were  ascribed  to  this  disease. 

In  these  cases  the  deafness  results  from  destructive  changes  in  the 
internal  ear  which  have  resulted  from  extension  of  the  inflannriatory 
process  from  the  middle  ear. 

The  Heart. — Endocarditis,  pericarditis,  and  myocarditis  are  rare 
complications  of  measles.  Inflammation  and  degeneration  of  the 
cardiac  muscle  may  occur  in  malignant  cases,  particularly  when  there 
is  hyperpyrexia.  We  recall  a  malignant  family  epidemic  some  years  ago 
which  destroyed  the  lives  of  the  three  children  of  the  household.  The 
first  child  sat  up  in  bed  during  convalescence  and  dropped  back  dead. 
The  other  two  succumbed  to  a  profound  toxaemia. 

Cases  of  endocarditis  have  been  reported  by  Martineau,  West,  and 
Kobler.  Hutchinson^  records  4  cases  in  which  mitral  murmurs  developed 
during  the  course  of  measles,  and  Cheadle  refers  to  2  cases  found  in  the 
post-mortem  records  of  Great  Ormond  Street  Hospital.  Gomby  dis- 
covered mitral  insufficiency  in  a  girl  nine  years  old,  after  an  attack  of 
measles.  Although  Sansom*  states  that  the  influence  of  measles  in 
predisposing  to  endocarditis  has  been  much  underrated,  most  writers 
are  of  the  opinion  that  this  complication  is  a  rarity. 

Pericarditis,  according  to  Autenrieth,  is  not  infrequent.  Cases  have 
been  reported  by  Berndt,  Majer,  Espinouse,  Braun,  Siegel,  Metten- 
heimer,  and  Heyfelder.^  When  pericarditis  occurs  it  is  apt  to  be  asso- 
ciated with  a  pleuropneumonia. 

Kidneys. — Renal  complications  are  rare  in  measles,  their  infrequenCy 
coiitrasting  sharply  with  their  prominence  in  scarlatina.  Nevertheless, 
Baginsky  says  that  his  recent  experience  leads  him  to  believe  that  they 
would  be  discovered  more  often  if  carefully  looked  for. 

1  Behandlung  der  bei  Infectionskrankheiten  Vorkommenden  Ohraffectionen,  loc.  cit.,  p.  581. 
-  Deaf-mutism,  a  Clinical  and  Pathological  Study,  Glasgow,  1896  ;  cited  by  Dawson  Williams, 
loc.  cit. 
3  Med.-Chir.  Trans.,  1891,  vol.  xxiv.  *  Quoted  by  Williams,  loc.  cit. 

^  Mentioned  by  Thomas,  loc.  cit. 


512  MEASLES 

Febrile  albuminiiria  of  brief  duration  is  not  uncommon  in  well- 
pronounced  attacks  of  measles,  as  in  other  infectious  processes  accom- 
panied by  fever.  When  the  kidneys  are  seriously  involved  there  may 
be  general  anasarca,  as  in  cases  reported  by  Abeille,  Denizet,  and  Comby 
(2  cases).  Ascites  and  anasarca  may,  however,  occur  without  albumin- 
uria, at  times  in  association  with  chronic  diarrhoea. 

Cases  of  true  nephritis  have  been  placed  on  record  by  Geissler,  Roser, 
Frank,  Rilliet,  West,  Kjellberg,  Lehman,  Bouchut,  Malmsten,  Spiess, 
Hauner,  Steiner,  Neuretter,  Zehnder,  and  Thomas,  who  cites  these 
various  writers.  Fatal  cases  with  ursemic  symptoms  have  been  reported 
by  Miiller,  Demme,  Browning,  and  Zichy-Woinarski.^ 

Vulvitis.— ^ Among  715  cases  of  measles  treated  in  isolation  pavilions, 
Comby  observed  vulvitis  twenty-five  times,  an  incidence  which  he 
thinks  was  kept  relatively  infrequent  through  systematic  antiseptic 
irrigations.  The  inflammation  of  the  vaginal  orifice  and  vulva  begins 
early,  as  a  rule,  and  may  persist  for  some  time.  The  parts  are  red, 
swollen,  covered  with  a  mucopurulent  discharge,  and  extremely  tender. 
Micturition  is  accomplished  with  considerable  pain.  In  some  cases 
vulvar  ulceration  occurs  and  more  rarely  gangrene. 

Glands. ^ — ^A  moderate  grade  of  adenopathy  is  a  part  of  the  normal 
symptomatology  of  measles.  In  some  cases  the  lymphatic  glands 
become  greatly  enlarged,  particularly  in  the  cervical  region.  In  rare 
cases  suppuration  may  take  place,  as  in  cases  mentioned  by  Gregory 
and  Rilliet. 

In  other  cases  the  glandular  enlargement  may  persist  for  a  long  time 
and  eventually  terminate  in  glandular  tuberculosis.  This  is  particularly 
true  of  the  bronchial  glands.  Fichtbauer,  Thore,  Eiseman,  Bufalini, 
and  Battersey^  have  reported  cases  of  inflammation  of  the  parotid  gland 
accompanying  measles,  and  Seidl,  Schultze,  and  Kellner  have  seen  the 
parotids  involved  at  a  later  period. 

Purpura. — Hemorrhages  developing  late  in  the  course  of  the  disease 
or  during  convalescence  should  not  be  interpreted  as  evidence  of  malig- 
nant hemorrhagic  measles,  but  as  a  secondary  and  superadded  condition. 
Nearly  all  of  the  exanthemata  may  at  times  be  complicated  at  a  late 
stage  by  the  development  of  hemorrhages  into  the  skin  and  from  the 
various  mucous  membranes,  including  the  kidneys  and  intestines. 

Masarei^  saw  eight  patients  convalescing  from  measles  attacked  with 
fever,  dropsy  without  albuminuria,  and  "scurvy,  mostly  in  the  form  of 
purpura;"  all  of  the  cases  ended  fatally.  Gley*  saw  intense  purpura 
hemorrhagica,  together  with  scorbutic  appearances  in  the  mouth,  some 
days  after  the  disappearance  of  the  measles  rash. 

Gangrene. — iVlthough  gangrene  is  not  a  common  complication  of 
measles,  it  appears  to  occur  more  often  after  this  infection  than  any 
other,  excepting,  of  course,  cutaneous  gangrene  in  smallpox. 

The  necrosis  is  apt  to  take  the  form  variously  designated  as  cancrum 
oris,  gangrenous  stomatitis,  or  noma.     This  formidable  complication 

1  Australian  Medical  Gazette,  October  15, 1893. 

2  Quoted  by  Thomas.  ^  Quoted  by  Thomas,  p.  104.  *  Quoted  by  Thomas. 


COMPLICATION H  AND  HI':Q(J I<:L/I<:  of  Mf'JASLI'JS 


01.3 


commonly  (lf;vel()])S  during  Uk;  dcdinc  of  the  (inipflon.  If  is  r;ffr;n 
associated  With  or"|'5TCred'prt-hynTTTi}ccr,ativ(;  sfoiniiiifis.  'J'lic  syjnpforn.s 
that  first  attract  attention  arc  salivation  ;in(l  a  fetid  breath.  If  the 
mouth  is  inspected  there  will  usually  he  found,  })etween  tlie  commissure 
of  the  mouth  on  the  alVected  side  and  the  opein'ng  r)f  Steno's  duct,  a 
vesicular  elevation  of  a  violaceous  color;  this  becomes  f^radually  darker 
and  finally  gives  way  to  a  blackish,  pultaceous  mass.  The  corresponding 
portion  of  the  cheek  on  the  exterior  is  swollen  and  of  a  wax-like  pallor. 
Soon  a  bluish-red  spot  appears,  which  l)ecomes  gangrenous  and  breaks 
through.  From  tl)is  point  the  necrosis  now  spreads  in  all  directions. 
The  spreading  border  is  surrounded  by  a  dusky-red  zone  which  is  firm 
and  infiltrated.  The  immediate  spreading  edge  shows  a  raising  up  of 
the  epidermis  in  the  form  of  a  vesicular  ring.    There  may  be  an  extension 


Fatal  cancrum  oris  after  measles.    The  necrotic  tissue  has  been  removed,  exposing  to  view  the 

alveolus  and  teeth. 


of  gangrene  from  one-quarter  of  an  inch  to  an  inch  in  twenty-four  hours. 
The  gangrenous  process  m  severe  cases  involves  the  entire  cheek  and 
the  greater  part  of  the  nose  and  hps.  It  has  been  known  to  attack  the 
ear,  the  eyelids,  and  a  considerable  portion  of  the  neck.  I'sually  the 
patient  dies  of  exhaustion  before  such  ravages  are  possible.  In  a  small 
proportion  of  cases  the  gangrene  ceases,  a  line  of  demarcation  is  formed, 
and  the  sphacelated  tissues  are  gradually  thrown  off.  In  such  instances 
the  deformity  must  subsequently  be  remedied  by  a  plastic  operation. 
In  the  fatal  cases  there  is  great  prostration,  the  child  takes  nourishment 
with  difficulty,  and  deatli  takes  place  ordinarily  in  from  one  to  two  weeks. 
A  horrible  odor  emanates  from  the  patient,  which  pervades  the  entire 
room  in  whicli  he  lies. 

There  is  a  less  serious  form  of  gangrenous  stomatitis  in  which  the 

33 


514 


MEASLES 
Fig.  S3 


Cancrum  oris  complicating  measles.    Photograph  taken  two  days  after  the  cutaneous  tissues 

became  involved. 

Fig.  84 


Same  patient  as  Fig. 


showing  the  spread  of  the  gangrene.    Photograph  taken  three  ( 
after  the  previous  picture. 


COMPLICATION H  AND  HI':QUI<:L/K  OF  MFASLFS  515 

necrotic  process  is  limited  to  the  iiiiieoiis  inciriljraiif;  and  fjoriy  tissues 
of  the  mouth.  Tliis  (lommonly  lias  its  orif^iu  uhout,  fhc  ^ums  and 
alveolar  process.  After  the  loss  of  some  of  the  teeth  and  a  jjortion  of 
necrosed  alveolus,  the  process  may  cease  and  recovery  take  place.  In 
some  cases,  however,  this  hony  necrosis  is  merely  j)art  of  the  general 
gangrenous  process  wliich  attacks  the  cheeks. 

The  necrotic  process  may,  in  rare  cases,  attack  the  genitalia,  particu- 
larly of  female  children,  giving  rise  to  the  condition  known  as  noma 
jiudendi.  The  course  of  the  gangrene  does  not  differ  from  that  involving 
the  mouth. 

Fig.  85 


^^^^^^^ 

|P^^^ 

'%.    ' 

P 

-*•■'<►,■., 

ma^A 

gjjIH 

1 

5 

k. 

..J.  — 

.^H 

Same  patient  as  Figs.  S3  and  81.    Pliotograpli  taken  alter  deatti  on  the  eighth  day  after  the 
beginning  of  the  gangrene,  and  three  days  after  Fig.  84. 

Measles  has  preceded  about  one-half  of  the  cases  of  cancrum  oris 
on  record.  In  106  cases  of  siangrene  of  the  mouth,  Tourde  found  41 
to  follow  or  accompany  attacks  of  measles.  Caillout  and  Bouley,  in 
46  cases  of  gangrene  of  the  mouth,  noted  measles  as  an  antecedent  dis- 
ease in  40  instances.  Mahieux  saw  measles  produce  gangrene  of  the 
mouth  in  3  out  of  11  cases.  Thus,  in  163  cases  of  gangrene  of  the 
mouth  measles  preceded  in  84,  or  over  50  per  cent.^ 

Rilliet  and  Barthez  observed  11  children  with  measles  attacked 
with  gangrene;  the  localization  was  as  follows:  gangrene  of  the  mouth, 
8  times;  gangrene  of  the  lungs,  4  times;  gangrene  of  the  pharynx,  3 
times;  gangrene  of  the  larynx,  once.  The  gangrene  appeared  in  several 
localities  in  some  of  the  patients.     INIoynier  saw  6  cases  of  gangrene  in 

1  Mentioned  by  Moynier.    Des  accidents  graves  de  la  rougeole,  etc.,  Metz,  1S60. 


516  MEASLES 

measles.  In  4  cases  the  vulva  was  attacked,  2  dying.  Gangrene  was 
noted  five  times  attacking  the  skin,  the  following  regions  being  selected : 
abdomen,  face  (twice),  arm,  and  buttock.  A  number  of  other  cases 
of  gangrene  of  the  mouth  were  observed.  Pneumonia  and  diarrhoea 
were  frequent  .complicating  conditions. 

Hildebrandt^  and  Perthes^  from  the  literature  have  collected  133  cases 
of  cancrum  oris  in  which  the  antecedent  or  accompanying  disease  is 
mentioned.  Noma  accompanied  or  followed  measles  in  53  cases.  The 
diseases  are  as  follows:^  measles,  53  times;  typhoid  fever,  26  times; 
chronic  diarrhoea,  21  times;  scrofula,  19  times;  smallpox,  9  times; 
diphtheria  and  measles,  twice;  diphtheria  and  typhoid,  once;  diphtheria 
of  the  genitalia,  once;  diphtheria  and  scarlet  fever,  once. 

The  affection  is  extremely  rare  in  infancy  and  beyond  the  age  of 
puberty;  it  may  be  remarked  that  measles  is  also  uncommon  during 
these  periods.  Von  Bruns*  collected  413  cases  of  noma,  among  which 
only  6  cases  occurred  in  infancy. 

The  cause  of  noma  is  but  poorly  understood.  It  has  been  variously 
attributed  to  embolism,  nerve  involvement,  the  use  of  mercury,  and 
infection  with  some  necrotizing  micro-organism.  The  last-named 
theory  is  doubtless  correct,  although  the  identity  of  this  microbe  does 
not  appear  to  have  been  determined. 

Walsh^  made  a  careful  bacteriological  study  of  8  cases  of  noma 
occurring  in  a  home  for  children  in  Philadelphia.  It  is  an  interesting 
fact  that  these  cases  occurred  during  a  period  of  two  and  one-half 
years.  The  diphtheria  bacillus  was  recovered  by  culture  from  each 
case.  Inoculation  and  tinctorial  tests  were  employed  to  identify  the 
Klebs-Loeffler  organism.  Most  of  the  cases  followed  measles,  but 
several  occurred  after  diphtheria.  Four  of  the  cases  began  with  ulcer- 
ative stomatitis.  A  number  of  the  cases  of  ulcerative  stomatitis — 15  in 
all — were  cultured,  but  diphtheria  organisms  were  not  found.  Walsh 
states  that  "since  noma  is  a  species  of  moist  gangrene,  requiring  probably 
from  analogy  two  different  micro-organisms,  one  a  saprophyte  to  produce 
putrefaction,  another  a  parasite  to  produce  primary  necrosis,  it  is 
possible  that  in  these  cases  where  diphtheria  bacilli  are  found  they 
may  be  the  primary  causative  agents.  When  other  pathogenic  micro- 
organisms capable  of  producing  necroses  are  found,  it  is  possible  that 
they  may  be  the  primary  excitants." 

The  above  investigation  is  of  considerable  interest,  particularly  in 
view  of  the  painstaking  manner  in  which  it  was  carried  out.  The  result, 
however,  is  scarcely  in  harmony  with  our  clinical  experience.  W^e  have 
observed  4  cases  of  fatal  cancrum  oris  within  recent  years;  3  occurred 
with  measles  following  scarlet  fever,  the  other  with  measles  alone.  We 
have  never  had  a  case  of  noma  develop  in  the  diphtheria  wards,  although 
on  a  number  of  occasions  measles  has  broken  out  there. 

1  Dissertation,  Berlin,  1873.  2  Verhandl.  deutsch.  Gesellsch.  f.  Chir.,  28  Kongress. 

3  Mentioned  by  Walsh.    Diphtheria  Bacilli  in  Noma.    Proceedings  of  the  Philadelphia  Patho- 
logical Society,  June,  1901. 
*  Handbuch  der  prakt.  Chir.,  Band  i.,  Abth.  2.  ^  Loc.  cit. 


(JOMf'fJC'ATIONS  AND  HKQd NIjA':  OF  ATh'ASfJ'JS  .017 

Noma  is  regarded  l)y  Matzenauer^  as  a  form  of  hospital  gangrene,  fjut 
feebly  contagious  and  requiring,  as  a  rule,  a  severe  preceding  disease 
to  produ(;e  a  predisposition.  He  discredits  tlie  rliplitluiria  bacillus  as 
an  etiological  factor,  and  believes  the  exciting  organism  is  the  same 
anaerobic  rod-sha])cd  bacillus  that  is  found  in  }iosf)itaI  gangrene. 

One  fact  is  undoubted,  that  measles  for  some  reason  more  strongly 
predisposes  to  the  development  of  noma  than  any  other  affection. 
Babes  and  Zambilovici^  announce  that  they  have  discovered  a  very 
small  bacillus,  cultures  of  which  injected  into  the  cheek  of  a  rabbit 
have  given  rise  to  gangrene  similar  to  noma. 

The  mortality  of  noma  is  frightful,  about  70  per  cent,  of  the  patients 
succumbing  to  the  disease. 

Pregnancy.— Measles  in  'pregnant  women  is  uncommon,  inasmuch  as 
most  individuals  pass  through  an  attack  of  measles  in  childhood.  As 
is  true  of  nearly  all  infectious  diseases,  the  development  of  measles  in 
parturient  women  is  apt  to  prematurely  terminate  the  pregnancy. 
Rosch  has  reported  a  case  of  abortion  terminating  fatally  as  a  result 
of  measles. 

Incidental  Improvement  in  Chronic  Diseases  After  Measles.^ — 
Every  infectious  disease  produces  a  certain  systemic  comraotionor  change; 
this  may  favor  the  development  of  diseases  to  which  the  patient  may 
be  inclined.  On  the  other  hand,  existing  diseases,  sometimes  of  long 
duration,  may  disappear  after  such  a  systemic  shaking-up.  Thomas 
has  collected  a  number  of  interesting  instances  from  which  we  freely 
quote. 

Behrend  saw  an  eczema  of  the  scalp  of  three  years'  duration,  in  a 
woman  of  forty  years  of  age,  permanently  cured  after  an  attack  of 
measles.  The  curative  influence  of  measles  upon  long-standing  diseases 
of  the  skin  has  also  been  attested  by  Rilliet,  Taupin,  Guersent,  and 
Rayer.  Barthez  and  Rilliet  saw  chorea,  epilepsy,  and  incontinence  of 
urine  of  several  months'  duration  get  well  after  measles. 

According  to  Weisse,  a  girl  who  suffered  from  convulsions  was 
entirely  cured.  Guersent  noticed,  with  the  beginning  of  the  fever  of 
measles,  permanent  relief  from  epileptiform  seizures,  of  which  the 
patient  had  had  several  a  day  for  a  long  time.  Schmidt  saw  a  six- 
year-old  girl,  who  had  had  daily  convulsions  that  had  so  reduced  her 
strength  that  death  was  expected,  completely  recover  after  measles. 
Feith  and  Schroder  van  der  Kolk  report  the  case  of  a  woman  who  for 
five  years  was  confined  to  an  asylum  because  of  violent  attacks  of  mania, 
who,  after  measles,  was  cured  and  discharged  from  the  institution. 
Hildebrandt  saw  an  obstinate  disease  of  the  joints,  which  had  been 
unsuccessfully  treated  for  three  years,  promptly  get  well  after  con- 
valescence from  measles.  Schmidt  noted  an  almost  magical  recovery 
in  a  five-year-old  boy  with  contraction  of  the  lower  extremities  of  six 
months'  duration.  Of  course,  such  examples  of  the  accidental  curative 
influence  of  an  attack  of  an  infectious  disease  are  met  with  not  only 

I  Arch.  f.  Derm.  u.  Syph.,  1902,  No.  60,  p.  373.  a  Quoted  by  Koger,  loc.  cit,  p.  402. 


518  MEASLES 

after  measles,  but  also  at  times  after  other  processes.  Mention  is  made 
elsewhere  of  a  raving  maniac,  confined  in  an  insane  asylum,  who  was 
completely  cured  after  an  attack  of  smallpox. 

Coincidence  of  Measles  with  Other  Infections. — Measles  may  be 
complicated  by-  almost  any  of  the  known  infectious  diseases.  In  the 
association  of  several  infectious  processes  measles  may  be  the  primary 
disease,  or  it  may  develop  secondarily  after  some  other  infection.  We 
have,  on  a  number  of  occasions,  seen  measles  complicate  diphtheria 
and  scarlet  fever.  We  are  inclined  to  believe  that  the  prognosis  is  more 
serious  when  measles  is  the  secondary  infection  than  when  some  other 
disease  is  engrafted  upon  it.  We  have  seen  measles  develop  during 
convalescence  from  smallpox  and  have  also  observed  the  reverse  order. 

In  the  vast  majority  of  cases  the  one  disease  develops  during  the 
decline  of  the  other.    We  have  never  seen  measles  in  its  early  eruptive 

Fig.  86 


Boy  exhibiting  eruption  of  measles  wliich  developed  during  convalescence  from  smallpox. 

stage  complicated  by  a  second  infectious  disease.  Measles  and  whooping- 
cough  seem  to  succeed  each  with  more  frequency  than  any  other  disease. 
Among  166  cases  of  measles,  Bernardy^  saw  pertussis  develop  in  21 
instances. 

THE  PATHOLOGY  OF  MEASLES. 

Skin. — At  autopsy  the  eruption  of  measles  is  not  visibla .unless,^  ^^^.^ 
^as  been  HfEinic  extravasation  into  the  skin. 

The  skin  has  been  studied  histologically  by  Neumann,  Catrin,  and 

Unna.     Neumann^  found  as  the  chief  changes  a  round-cell  infiltration 

,  about  the  l)loodvessels,  hair  follicles,  and  sweat  glands.    Catrin^  likewise 

observed  a  pronounced  infiltration  of  leukocytes,  but  in  addition,  in  the 

nodular  form  of  measles,  a  series  of  changes  in  the  deep  epidermal  cells. 

1  Annals  of  Gynecology  and  Pediatrics,  July,  1894. 

2  Histolog.  Veranderungen  der  Haut.  bei  Masern  u.  Scharlach,  Med.  Jahrb.,  1882,  p.  159. 

3  Les  alterations  de  la  peau  dans  la  rougeole,  Archiv.  de  med.  exper.,  .1891,  No.  2;   quoted  by 
Unna. 


77//';  I'ATIIOIJXIV  O/''  Mf'JASfJ'JS  519 

These  consistcMl  of  a  colloid  (l(;^eneration  of  tin;  perinuclear  /one  <)\'  soiric 
of  the  (l('ej)-lyin^  e|)i(,heli!il  (lells.  Around  the  areas  of  colloid  cliarige 
were  dilated  interepithelial  spaces  eontaininj^  coagulated  fibrin  and  leuko- 
cytes. In  the  centre  of  the  papule  the  colloid  masses  run  together  and 
undergo  coagulation  necrosis,  tliis  taking  place  in  the  fjrickle  layer. 

Catrin  only  found  emigration  of  leid\ocytes  from  the  pajnllary  hlcjofl- 
vessels  at  those  places  where  the  surface  ej)ith('lium  contained  cf^lloid 
cells.  Unna  regards  the  colloid  change  and  necrosis  of  the  epithelium 
as  the  result  of  the  direct  influence  of  the  poison  of  the  disease  upon 
the  epidermal  structures. 

Unna'  states  that  in  measles  a  spastic  resistance  in  the  cutaneous 
vessels  is  added  to  the  primary  congestive  hypenemia  which  develops 
around  the  infection  in  the  capillaries,  and  this  explains  the  cyanotic 
color,  the  papular  swelling,  and  the  urticarial  oedema  of  the  centre,  as 
well  as  the  frequent  escape  of  coloring  matter  of  the  blood.  The  rapidly 
developing  spastic  oxlema  always  collects  at  the  place  of  least  resist- 
ance, which,  in  children,  is  in  the  fatty  tissue  around  the  coil  glands 
and  in  the  sheaths  of  the  larger  vessels,  the  cutaneous  muscles  and  fol- 
licles. The  individual  coils,  the  hair  follicles,  and  the  muscles  seem  to 
swim  free  in  widely  dilated  spaces. 

Dilated  lymph  vessels  and  enormously  distended  lymph  spaces  are 
seen  m  the  lower  and  central  parts  of  the  cutis.  Another  characteristic 
is  the  almost  complete  absence  of  a  cellular  exudate.  Leukocytic 
emigration  is  not  more  than  in  all  simple  stagnatory  hyperpemias,  less, 
indeed,  than  in  most.  But  a  few  leukocytes  are  found  in  the  epithelium. 
During  the  stage  of  scaling,  the  subbasal  horny  layer  separates  itself 
from  the  basal  and,  with  the  central  and  upper  horny  layers,  form  the 
scale.  The  lost  epithelium  is  replaced,  as  usual,  by  mitotic  proliferation. 
The  above  description,  Unna  remarks,  refers  merely  to  the  ordinary 
flat  or  slightly  papular  eruption. 

Mucous  Membranes. — The  mucous  membrane  of  the  nose,  mouth, 
pharynx,  larynx,  trachea,  and  bronchi  is  the  seat  of  a  catarrhal  inflam- 
mation. The  epithelial  cells  undergo  a  colloid  change  and  are  often 
swollen  and  detached.  The  lymph  follicles  and  the  surrounding  struct- 
ures are  infiltrated  with  cells.  Occasionally  when  the  inflammation  is 
intense  the  follicles  may  break  down  and  form  ulcers.  At  times  such 
ulceration  m  the  larynx  may  lead  to  involvement  of  the  cartilage. 
Slawyk,^  in  a  histological  study  of  the  oral  mucous  membrane,  found  the 
epithelium  thickened  and  in  places  undergoing  fatty  degeneration,  giving 
rise  to  the  whitish  dots  described  by  Koplik. 

Steiner^  observed  in  several  cases,  at  autopsy,  a  blotchy  redness  of  the 
mucous  membrane  of  the  larynx  and  bronchi,  and  Wilson,  Eisenmann. 
Rayer,  and  Gerhardt  saw  a  similar  condition  in  the  trachea  and  bronclii. 

Heyfelder,^  one  of  the  older  writers,  describes  an  eruption  similar  to 
that  on  the  skin  in  the  duodenum,  jejunum,  and,  at  times,  in  the  stomach 

1  Histopathology  of  the  Skin,  translated  by  Dr.  Norman  Walker,  1900. 

'  Deutsch.  med.  Wochenschrift,  April  28, 1898 ;  quoted  by  Corlett. 

*  Quoted  by  Thomas,  loc.  cit.,  American  edition,  p.  72.  *  Quoted  by  Thomas. 


520  MEASLES 

and  ileum;  this  has  been  noted  also  by  several  other  observers.  More 
recently  Steiner^  mentions  a  blotchy  redness  of  the  intestinal  mucous 
membrane  occurring  in  children  dying  during  the  eruptive  stage. 

According  to  Worthington/  the  lymphatic  follicles  and  Peyer's  patches 
of  the  bowel  may  undergo  destructive  ulceration,  leading  even  to  perfora- 
tion. Thomas  says  that  Fuchs  saw,  upon  the  genital  mucous  membrane, 
numerous  red,  somewhat  puffy  spots  overspread  with  mucus.  This 
observation  was  likewise  made  by  Henoch  and  Chomel. 

Lymphatic  Glands. — ^The  lympha,tic  glands  are  enlarged  in  measles,_ 
but  to  a  less  extent  than  in  scarlet  fever.  When  bronchopneumonia  Ts 
■present  the  tracheobronchial  glands  may  be  found  distinctly  swollen. 
In  a  certain  proportion  of  cases  the  glands  show  evidences  of  tuberculosis. 
Loomis,  Pizzini,  and  Kalbe^  found  tubercle  bacilli  in  apparently  normal 
tracheobronchial  glands;  the  last-named  observer  noted  the  presence  of 
these  bacilli  in  8  per  cent,  of  apparently  healthy  glands.  It  is  suggested 
that  these  lie  dormant  until  an  attack  of  measles  or  some  other  affection 
involving  these  glands  stimulates  the  tuberculous  process  to  activity. 

Lungs. — Bronchopneumonia  is  present  in  a  large  proportion  of  the 
fatal  cases.  The  process  is  not  essentially  different  from  that  observed 
in  bronchopneumonia  independent  of  measles  save  that  there  is  a  more 
pronounced  tendency  in  many  cases  to  suppuration.  It  is  not  rare  for 
the  pulmonary  trouble  to  eventuate  in  tuberculosis,  exhibiting  usually 
the  form  of  a  caseous  pneumonia. 

Cornil  and  Babes*  have  described  a  peripneumonia  which  occurs 
early  in  the  so-called  suffocative  cases,  and  which  they  regard  as  peculiar 
to  measles.  It  begins  in  the  lymphatic  tissue,  involves  the  interlobular 
and  interalveolar  structures,  and  leads  to  fibrinous  exudation  into  the 
air  vesicles. 

StiebeP  speaks  of  a  blotchy  redness  of  the  pleural  membranes  which 
he  observed  in  four  autopsies.  They  were  sharply  contoured,  red  spots, 
apparently  situated  just  beneath  the  pleura  on  both  sides. 

Roger  observed  a  purulent  pleurisy  during  convalescence  from 
measles  in  a  five-year-old  child. 

The  sfleen  is  moderately  swollen  in  measles,  although  this  is  more 
often  determined  at  autopsy  than  at  the  bedside. 

Liver." — Freeman''  found  focal  necrosis  of  the  liver  in  4  out  of  14 
g^Utopsies  on  measles  cases.  The  larger  areas  of  necrosis  are  visible  to 
the  naked  eye  and  may  be  confounded  with  tubercle.  Microscopically 
there  is  a  sharply  circumscribed  roundish  area  of  necrosis  in  which  the 
cytoplasm  fails  to  stain,  and  fragmentation  of  the  nuclei  is  seen.  The 
condition  is  due  to  the  local  action  of  bacterial  toxins. 

Blood. — In   uncomplicated   cases  of   measles   the   condition   of   the 
;  blood  is  unaltered.    Fibrin  may  be  increased  when  the  catarrhal  symp- 
toms are  severe. 

1  Quoted  by  Thomas.  -  Quoted  by  Dawson  Williams. 

8  Mentioned  by  Roger,  loc.  cit.,  p.  1004.  *  Quoted  by  Williams,  loc.  cit. 

5  Quoted  by  Thomas,  loc.  cit. 

6  Result  of  Work  at  the  New  York  Foundling  Asylum.    Archives  of  Pediatrics,  February,  1900, 
and  New  York  Medical  Record,  1898,  vol.  liv. 


TIIK  BA(JTI<:h'l()l/)(!V  Oh'  M/'LASfJ-JS  521 

The  number  oi  red  cdls  is  nof,  strikingly  reduced  in  mild  or  moderate 
cases,  and  may  at  times  be  actually  increase;*!.  In  8  cases  Felsentlial 
counted  from  five  to  five  and  a  half  million  eorjjuscles.  I'lie  h;/'mo- 
globin  is  likewise  slifijhtly  or  not  at  all  reduced. 

The  v^hifc  r.rlh  not  only  are  not  increased  in  measles,  but  they  are 
often  reduced  below  tlie  iiormal.  In  8  cases  Rieder  noted  an  average 
of  7500  cells,  the  leukocytes  being  least  numerous  at  the  height  of  the 
disease,  and  increasing  as  the  fever  disappeared.  Cabot^  states  that 
during  convalescence  the  lymphocytes  and  especially  the  large  mono- 
,  nuclear  forms  are  increased. 

According  to  Coombe,  uniform  changes  occur  in  the  blood  in  the 
incubation  period.  Coonibe^  ^^J^.}  "In  the  incubation  period  of  measles 
tliere  is  a  hyperleukocyfosis  M'ithout  other  symptoms.  Tliis  is  a  constant 
siii;n  of  the  inc.ubation  period.  During  the  last  two  days  of  the  period 
of  invasion  or  exanthem,  and  throughout  the  entire  period  of  the 
*e:tanthem:,  there  is  a  hypoleuJcocytosis." 

'-■  These  alterations  are  due  to  the  change  in  the  number  of  the  poly- 
morphonuclear neutrophiles.  These  observations  were  confirmed  by 
Platenga,^  Avho  also  found  similar  changes  in  rubella. 

The  eosinophile  cells  are  usually  decreased  or  normal  in  number. 
Cabot  found  the  differential  counts  normal;  Felsenthal  found  the  poly- 
morphonuclear cells  much  increased  and  eosinophiles  never  over  1 
per  cent. 

In  cases  in  which  the  diagnosis  between  scarlet  fever  and  measles 
is  obscure,  a  differential  blood  count  should  1)6  of  distinct  value.  On 
the  other  hand,  the  examination  of  the  blood  is  of  no  particular  value 
in  differentiating  measles  from  rubella  (rotheln),  inasmuch  as  the 
cellular  constituents  are  much  the  same  in  the  two  diseases. 


THE  BACTERIOLOGY  OF  MEASLES. 

The  extreme  contagiousness  of  measles  is  proof  of  its  microparasitic 
origin;  some  reservation  must,  however,  still  be  expressed  as  to  the 
etiological  relationship  of  the  organisms  thus  far  described. 

Braidwood  in  1878  called  attention  to  a  bacillus  which  he  found  in 
measles  and  which  he  regarded  as  the  cause  of  the  disease.  Lombroso* 
described  cocci  in  the  rete  mucosum  of  the  measles  spots.  Similar  bodies 
were  found  by  von  Leyden  and  Fiirbringer. 

In  1892  Canon  and  Pielicke  found  in  14  cases  of  measles  a  bacillus 
which  they  considered  to  be  the  specific  causative  agent.  The  discovery 
was  made  possible  by  a  special  method  of  staining.'^  The  organism  was 
variable  in  size,  sometimes  quite  small  and  resembling  a  diplococcus, 

i  Clinical  Examination  of  the  Blood,  fourth  edition,  New  York,  1901. 

»  Archiv.  de  med.  des  enfants,  1903.  ^  Archiv.  de  nied.  des  enfants,  March,  1903. 

*  Lo  Sperimen.,  1884,  x. 

5  Stain  for  the  bacillus  of  Cauou  and  Pielicke.  Blood  is  thinly  spread  upon  a  clean  cover-glass 
and  fixed  by  five  to  ten  minutes'  immersion  in  absolute  alcohol.  Then  stain  with  the  following 
solution  and  incubate  at  37°  C.  for  from  six  to  twenty-four  hours  :  Concentrated  aqueous  solution  of 
methylene  blue,  40 ;  0.25  per  cent,  solution  of  eosin  in  70  per  cent,  alcohol,  20 ;  distilled  water,  40. 


522  MEASLES 

and  other  times  as  long  as  a  red  blood  cell.  It  was  present  in  the  blood, 
sputum,  and  secretions  of  the  nose  and  eyes  throughout  the  entire 
disease,  but  disappeared  when  convalescence  set  in.  The  bacillus  could 
be  grown  on  bouillon,  but  on  no  other  media. 

Czajkowski^  found  a  bacillus  in  the  blood  and  mucous  secretions  of 
50  cases  of  measles,  which  was  apparently  identical  with  that  above 
described.  It  grew,  however,  on  various  albuminous  media,  especially 
blood  serum  and  glycerin  agar,  but  not  on  gelatin  and  plain  agar. 
Inoculations  of  mice  produced  a  fatal  septicsemia.  Gregorieff,  in  an 
examination  of  the  blood  in  13  cases,  found  the  bacillus  in  each  case, 
and  grew  it  in  bouillon  in  10  instances. 

Josias^  failed  to  find  this  organism  in  a  study  of  the  blood  and  secre- 
tions of  24  cases,  and  Barbier  and  Warschovsky  also  obtained  negative 
results,  the  latter  examining  21  cases. 

Arsamakor,^  in  an  examination  of  665  cases  of  measles,  found  in  the 
blood  and  mucous  secretions,  grouped,  rod-shaped  bodies,  5  to  6  microns 
in  length,  having  bulbed  extremities. 

In  1900  Lesage*  published  the  results  of  a  study  of  200  cases  of 
measles.  He  found  a  delicate  micrococcus  which  grew  best  on  gelose 
(agar),  took  stains  slowly,  and  was  decolorized  by  Gram's  method. 
The  cultures  bore  a  resemblance  to  those  of  the  pneumococcus.  The 
organism  was  found  constantly  in  measles,  but  was  absent  in  25  cases 
of  scarlet  fever  and  in  45  normal  children.  In  53  children  who  had 
had  measles  previously  it  was  found  twice.  Rabbits  were  inoculated 
with  blood  and  nasal  secretions  in  many  cases,  and  measles  apparently 
reproduced  in  nearly  all. 

Von  Niessen^'  examined  the  blood  during  the  height  of  the  measles 
exanthem  and  found  a  bacillus  which  in  some  respects  resembled  that 
of  Canon  and  Pielicke.  It  produced,  however,  rose-colored  colonies  on 
gelatin  and  grew  well  also  on  glycerin  agar,  bouillon,  and  potato.  He 
designated  this  organism  "bacillus  roseus." 

In  1891  Doehle^  found  in  the  blood  of  8  cases  of  measles  certain 
bodies  which  he  regarded  as  protozoa.  In  fresh  blood  they  were  observed 
not  only  in  the  plasma,  but  also  in  the  red  blood  corpuscles.  After  the 
eruption  appeared  the  bodies  became  visible  almost  exclusively  in  the 
red  cells.  They  were  from  a  half  to  one  micron  in  diameter  and  exhibited 
an  opaque  nucleus  with  a  surrounding  clear  zone.  Later  larger  oval 
bodies  with  two  nuclei  were  seen. 

More  recently  Weber^  has  detected  bodies  in  the  blood  which  he 
regards  as  protozoa.  From  the  above  divergent  findings  it  is  evident 
that  further  research  is  necessary  before  any  of  the  organisms  described 
can  be  accepted  as  the  specific  cause  of  measles. 

1  Centralbl.  f.  Bakt.  u.  Parasit.,  1895,  Nos.  17  and  18. 
s  La  medecine  moderne,  Paris,  June  2,  1902. 

3  Article  abstracted  in  Revue  de  miSdecine,  1899,  vol.  xix.  p.  561. 

4  Bulletin  de  la  Soci^tt^  des  hOpitale  de  Paris,  March  15-22,  1900. 
6  Arch.  f.  Derm.  u.  Syph.,  1902,  vol.  Ix.  p.  429. 

6  Centralbl.  f.  allgem.  Path.,  etc.,  1892,  iii.  p.  150. 

7  Centralbl.  f.  Bakt.  u.  Parasit.,  1897,  vol.  xxi.  p.  286. 


77//';  l)fA(JN()S/S  (}/<•  M/'JASfJ'JS  f/Z' 


THE  DIAGNOSIS  OF  MEASLES. 


It  is  a  mii.ll<'r  of  f^rciU,  iinporlfuicc,  pjuliciihirly  in  iiishtutioiis  for 
cliiMnMi,  tlia-1,  t])v.  <li}i<i;n(),si,s  oi'  riiciislcs  he  iri;ul(;  id  as  early  a  date  as 
possible  in  order  that  the  s))rea(l  of  the  infeetion  may  be  prevented. 
Unfortunately  the  contafriuni  of  measles  is  transmitted  at  a  very  early 
})erio<l,  not  infref|uently  on  the  first  or  second  day  of  the  invasive  illness, 
and  before  the  dia|!;nosis  is  firndy  (>stablislied.  The  existenee  of  an 
epidemic  of  measles  or  knowled(i;(;  of  ('xpf)sure  to  th(^  disease  will  y;ijt 
the  physician  on  guard  and  often  enable  hiin  to  make  a  diagnosis,  or 
at  least  strongly  suspect  it,  upon  the  first  development  of  catarrhal 
symptoms.  The  statement  is  erjually  true  of  measles  and  smallpox, 
that  the  diagnosis  cannot  be  indubitably  made  before  the  appearance 
of  the  eruption,  although  when  all  of  the  invasive  symptoms  are  typi- 
cally developed,  when  there  has  been  exposure  to  the  disease,  and, 
particularly  when  the  characteristic  buccal  enanthem  is  present,  the 
diagnostic  probability  approaches  almost  to  a  certainty.  _As  in  small- 
pox.  th^  v;^ccinal  condition  of  the  patient  often  constitutes  information 
of  important  diagnostic  value,  so  in  measles  does  the  history  as  to 
p-e vioiTs'allacks .  It.js  generally  agreed  that  second  attacks  of  measle.s. 
are  of  great  rarity.  In  a  doubtful  case,  an  authentic  history  of  a  pre- 
vious attack,  of  measles  would  constitute  strong  presumptive  evidence 
against  the  rubeolous  nature  of  the  disease  under  consideration. 

While  the  diagnosis  of  measles  is  usually  announced  when  the  eruption 
appears,  it  must  not  be  thought  that  the  rash  is  in  itself  all-sufficient 
evidence. 

The  eruption  of  measles  is  merely  its  most  conspicuous  manifestation. 
T^ P,g!he,<j!  iiidjstipcrnisihn ble  from  the  measles  exanthem  may,  at  times, 
appear  in  other  diseases.  I'lie  diagnosis  is  to  be  made  by  attention  to 
T^!!fi^S%T^the''cai:'aTrhal  symptoms,  the  fever,  and  the  eruption,  both 
upon  the  sldn  and- buccal  mucous  membrane.  A  due  sense  of  proportion 
musFBe  cultivated  so  that  the  presence  or  absence  of  certain  symptoms 
may  be  accorded  its  proper  value. 

Ordinarily  the  diagnosis  of  measles  presents  no  difficulties.  When, 
however,  the  disease  appears  in  unusual  guise,  in  extremely  mild  or 
malignant  or  irregular  form,  the  determination  of  the  nature  of  the 
disease  may  be  most  perplexing.  Especially  is  this  true  in  those  rare 
cases  of  measles  without  eruption;  in  such  instances  the  diagnosis  can 
only  be  made  when  the  history  and  the  entire  clinical  picture,  save  the 
eruption,  bespeak  measles. 

Diagnostic  Value  of  the  Enanthem  or  Mucous-membrane  Eruption 
(Koplik's  Spots).— It  is  stated  by  Northrup^  that^]y[ie  typical  buccal 
s£ots  are  present  in  measles  in  about  91  per  cent,  of  cases,  that  they 
are  seeiTonly^m  measles,  and  that  they  .ordinarily  appear  from  one-to 
tlaj:ee~da.ys.^be£ore  the  cutaneous  eruption. 

Our  own  experience  would  confirm  this  statement.    We  have  observed 

1  Von  Jilrgensen's  article  on  Measles  in  Nothnagel's  Encyclopedia  of  Practical  Medicine,  American 
edition ;  additions  by  Northrup. 


524  MEASLES 

the  spots  as  early  as  thi:ee  days  before  the  appearance  of  the  cutaneous 
exanthem.  We  have  never  seen  mese^'^pots  in  rubella,  scarlatma,  or 
any  other  disease  save  measles. 

Rotch,  of  Boston,  reflects  the  general  opinion  in  the  following  state- 
ment: "The  presence  of  Koplik's  spots  helps  in  a  large  majority  of 
cases.  The  consensus  of  medical  opinion  appears  to  be  that  while 
their  absence  does  not  exclude  measles,  their  presence  is  pathognomonic 
of  measles." 

Sevestre^  insists  upon  the  diagnostic  importance  of  the  erythema  of 
the  soft  palate  which  precedes' by  one  or  two  days  the  exanthem  of 
measles.  "The  redness  is  not  uniform,  but  presents  itself  in  the  form 
.of^small,  rounded  or  irregular  spots,  which  are  sometimes  disseminated 
in  small  number  and  at  other  times  almost  confluent."  This  appearance 
of  the  soft  palate  to  our  minds  is  scarcely  sufficiently  peculiar  to  measles 
to  be  of  much  diagnostic  value. 

It  is  at  times  a  matter  of  importance  to  determine  during  conva- 
lescence the  nature  of  the  preceding  disease.  Measles  may  often  be 
diagnosed  by  the  brownish-red  stains  on  the  body  as  late  as  a  week  or 
ten  days  after  the  subsidence  of  the  eruption.  Inasmuch  as  children 
in  this  condition  may  be  capable  of  transmitting  the  infection,  it  is 
important  in  schools,  asylums,  or  other  institutions  for  children  to 
exclude  or  isolate  such  patients.  Not  infrequently  a  mild  grade  of 
blepharitis  persists  after  an  attack  of  measles. 

Rubella  (Rotheln). — This  afi^ection  is  more  apt  to  be  confounded 
with  measles  than  any  other.  Confusion  may  arise  when  measles 
presents  itself  in  very  mild  form  or  when  rubella  appears,  as  it  some- 
times does,  with  severe  manifestations.  .The  history  as  to  the  previous 
occurrence  in  the  patient  of  the  one  or  the  other  disease  is  evidence 
of  considerable  importance.  It  is  uncommon  for  measles  to  attack  an 
-.individual  twice  and  still  rarer  for  rubella  to  act  in  this  mannerr"""^ 

The  prodromal  stage  in  rubella  is  very  brief,  rarely  lasting  more  than 
twenty-four  hours';  the  catarrhal  symptoms  are  slight  or  absent.  It 
will  be  helpful  to  remember  that  catarrhal  manifestations  are  more 
pronounced  in  mild  cases  of  measles  than  in  severe  cases  of  rubella. 
.The  characteristic  buccal  spots  seen  in  measles  are  absent  in  rubella. 
The  fever  is  slight,  commonly  99°  or  100°  F.,  and  rarely  exceeding 
101°  F.;  it  is  of  short  duration.  The  eruption  in  rubella  spreads  more 
rapidly  than  in  measles  and  is  of  briefer  duration.  The  lesions  are 
slightly  elevated  macules,  of  a  pale  rose-red  color,  and  pinhead  to  .pea_ 
sized.  The  eruptive  elements  are  smaller,  paler,  and  more  discrete^ 
than  in  measles.  The  patient  with  rubella  often  feels  well  enough  to 
remain  out  of  bed.  A  more  exhaustive  differential  diagnosis  is  given 
in  the  chapter  on  Rubella. 

Scarlet  Fever. — It  is  only  in  anomalous  cases  that  scarlatina  is  apt 
to  be  confounded  with  measles;  ordinarily  the  differentiation  of  these 
affections  is  a  simple  matter. 

1  Quoted  by  Comby,  p.  195,  loc.  cit. 


77//';  /)fA(JN()SIS  OF  MI'JASLJ'JS  ,025 

IpL  scarlatina  the  onset  is  more  stormy,  with  hi(^}i  fever  and  a  much 
greater  tendency  to  vomiting.  Tlie  eruption  usually  comes  out  on 
ffie  second  day,  earlier  therefore  than  that  of  measles.  Diotophobia, 
coiy/a,  lioai-seness,  ;ind  cough  are  lacking  in  scarlatina,  but  instead  we 
''find  sore  tlnoat,  rniirkcd  glandular  enlargement  aV)Out  the  jaws,  and  a 
chai'ac  I  eristic  tongue.  The  peculiar  buccal  spots  of  measles  are  absent, 
tlie  oral  and  pharyngeal  mucous  membrane  showing  merely  congestion. 
The  faee  is  less  intensely  involved  by  the  rash  than  in  measles  and, 
■fnorcover,  shows  circumoral  ])allor. 

The  rash  in  scarlet  fever  is  diffuse  and  punctiform;  it  should  be 
remembered,  however,  that  on  the  arms  and  legs  it  is  not  infrer^uently 
blotchy  and  suggestive  of  measles.  The  subsequent  desquamation  is 
more  profuse  and  lamellar  in  character.  Otitis  media  and  albuminuria 
are  common  complications.  In  septic  cases  purulent  nasal  discharge  is 
not  uncommon  even  in  the  early  stages  of  the  disease;  laryngeal  symp- 
toms are,  however,  rare. 

^Confusion  may  result  in  those  cases  of  measles  in  which  there  is  a 
tendency  to  general  confluence  of  the  rash;  iisually  some  portions  of 
the  cutaneous  surface  will  exhibit  the  measly  character  of  the  rash. 
In  patients  seen  late  brownish  stains  on  the  body  speak  for  measles, 
and  pronounced  desquamation  on  the  hands  and  feet  and  albuminuria 
point  toward  an  antecedent  scarlet  fever. 

Influenza.^ — "La  grippe,"  particularly  that  form  accompanied  by 
catarrhal  inflammation  of  the  upper  air  passages,  may  present  a  con- 
Sirierable  resemblance  to  measles  during  the  invasive  stage.  It  is 
ihanifest  that  a  disease  beginning  with__fever,  cpryza,  and  cough  might 
readily  be  either  measles  or  influenza.  Photophobia,  which  is  justly 
regarded  as  a  significant  symptom  by  the  laity,  is  usually  well  marked 
in  measles  and  absent  in  influenza.  If  the  characteristic  bluish-red 
spots  with  whitish  specks  on  their  summits  be  visible  upon  the  buccal 
mucous  membrane  the  diagnosis  is  at  once  made  clear. 
""TTIie  presence  of  an  epidemic  of  one  or  the  other  disease  will  often 
aid  one  in  early  arriving  at  a  correct  diagnosis. 

Smallpox. — During  epidemics  of  smallpox,  cases  of  measles  are  not 
infre2[uently._ confounded  with  variola.  We  have  had  numerous  cases 
of  measles  sent  into  the  Municipal  Hospital  under  the  diagnosis  of 
smallpox.  On  the  other  hand,  the  reverse  error  is  by  no  means  rarely 
made.  It  is  particularly  the  severe  cases  of  smallpox  with  considerable 
turgescence  of  the  skin  that  simulate  measles.  Standing  some  feet  from 
the  patient  the  resemblance  in  these  cases  is  striking.  Some  cases  of 
measles  are  accompanied  by  a  considerable  degree  of  papulation;  when 
such  an  eruption  is  developed  by  an  adult  during  an  epidemic  of  small- 
pox, an  error  might  at  the  very  beginning  be  readily  made  (Fig.  S7i.  A 
further  point  of  resemblance  is  that  each  disease  is  preceded  by  a  pro- 
dromal stage  of  almost  the  same  duration. 

^_^il&_jConstitutional    symptoms    preceding    smallpox    are,    however, 

usuadly^more  severe  (temperature  104°  to  105°  F.),  and  are  commonly, 

"though    not    always,    accompanied    by    pronounced    backache.      The 


526 


MEASLES 


temperature,  moreover,  falls  a  few  days  after  the  appearance  of  the 

eruption,  while  the  fever  Tn  measles  continues  high  during  the  eraptiver 
stage.  --.>.:-.: ,--.«-u..:*,-.-,„,._.   ,.^.,   ,     :,■- 

The  catarrhal  symptoms  affecting  the  eyes  and  respiratory  passages, 
which  are  so  constant  in  measles,  are, absent  in  smallpox,  at  least  dur- 
ing the  prodromal  stage.  CJose^inspection  of  the  mouth  in  smallppj^ 
may  reveal  the  presence  upon  the  soft  palate  of  rounded,  glistening, 
pinhead-sized,  reddish  elevations,  but  these  differ  considerably  from  the 
bluish-red  spots  on  the  buccal  mucous  membrane  in  measles. 

The  maculopapules  of  measles  are  soft  and  velvety  to  the  touch,  as 
compared  with  the  firm,   shotty  character  of  the  smallpox  papules. 


Fig.  87 


Smallpox  on  the  second  day  of  tlic  erupLioii,  prcscntiiiL 

measles. 


resemblance  to  the  eruption  ot 


The  sweep  of  an  experienced  hand  over  the  skin  will  often  suffice  to 
differentiate  the  two  diseases.  Where  there  is  doubt,  twenty--fouiJiauxs,' 
^^ay  will  dispel  all  uncertainty,  for  by  this  time  the  eruption  of  measles 
will  have  become  flatter  and  more  diffuse,  and  the  papules  of  smallpox 
firmer  and  xnore  distinctly  elevated. 

The  prodromal  morbilliform  rash,  the  so-called  roseola  variolosa, 
may  be  confounded  with  measles.  This  eruption  occasionally  develops 
in  mild  cases  on  the  second  day  of  the  invasive  stage.  The  lesions  are 
non-elevated,  irregular  in  distribution,  of  brief  duration,  and  unaccom- 
panied by  catarrhal  symptoms. 

Typhus  Fever.— During  the  epidemic  prevalence  of  typhus  a  con- 
founding of  this  disease  with  measles  might  take  place  when  the  eruption 


77//';  l)fA(,'NOSlS  OF  MKAS/J'JS  .027 

is  profuse.  Pastau  is  (jiiofcd  hy  Tlioinas  as  saying'  fliat.  tlif  exanflicrn 
of  typlnis  is  by  no  incjiiis  rjircly  papiihir  or  even  li(!inorrhaf^i(;  like  that 
of  measles,  arid  a  catarrhal  afiectioti  of  the  air  passaf^es,  especially  of 
the  trachea,  is  one  of  its  usual  concomitant  symptoms.  The  fever  and 
nervous  symptoms  are  more  pronounced  in  typhus  and  there  is  {^reat 
enlargement  of  the  sj)leen;  the  eruption  is  usually  absent  on  the  face, 
and  oculonasal  catarrh  is  lacking.  We  recall  a  case  of  atypical  measles 
which  was  sent  to  the  Municipal  IIosj)ital  as  a  ca.se  of  typhus  by  one 
of  the  foremost  physicians  of  this  country. 

Roseola  Syphilitica. — The  macular  eruption  of  syphilis  has  on  more 
than  one  occasion  been  confounded  with  measles.  The  error  of  mis- 
taking syj)hilis  for  measles  may  be  made  when  the  ))atient  is  an  adult 
and  when  the  febrile  symptoms  are  mild.  On  the  other  haufl,  syphilis 
with  pyrexial  elevation  might  be  regarded  as  measles. 

The  eruption  of  syphilis  is  slower  in  development  and  the  lesions  are 
much  more  uniform  in  size  and  distribution.  The  face  is  but  slightly, 
if  at  all,  involved.  Usually  the  initial  lesion  or  the  hardened  remains 
thereof  can  still  be  discovered.  In  addition  otlier  evidence  of  the 
syphilitic  infection  maybe  present,  such  as  mucous  patches,  pronounced 
inguinal  adenopathy,  etc. 

Morbilliform  Erythemata. — There  are  a  number  of  conditions  in 
which  rashes  bearing  a  more  or  less  close  resemblance  to  that  of  measles 
may  occur.  They  may  be  divided  into:  (a)  accidental  rashes  accom- 
panying the  exanthematous  fevers,  (6)  drug  eruptions,  and  (c)  serum 
eruptions. 

Mention  has  already  been  made  of  the  resemblance  of  the  roseola 
variolosa  to  measles.  An  analogous  eruption,  roseola  vaccinosa,  develops 
occasionally  about  the  tenth  day  of  vaccination.  The  same  features 
which  have  been  referred  to  as  distinguishing  the  variolous  roseola  from 
measles  may  be  applied  to  the  vaccinal  rash.  jNIorbilliform  rashes  may 
in  rare  instances  be  observed  also  in  the  course  of  varicella,  scarlet  fever, 
and  other  infectious  diseases. 

Drug  Eruptions. — The  drugs  which  most  frequently  give  rise  to 
eruptions  simulating  measles  are  antipyrin,  quinine,  chloral,  copaiba, 
and  cubebs. 

The  most  common  eruption  resulting  from  the  administration  of 
aritipyrifi  is  a  morbilliform  erythema.  Of  52  instances  of  eruption  from 
the  use  of  antipyrin  collected  by  Spitz,  41  were  of  the  measles  type. 
The  eruption  may  be  generally  distributed  over  the  trunk  and  extremi- 
ties or  it  may  be  limited  to  certain  regions  thereof;  an  important  distin- 
guishing feature  is  that  the  face  is  usually  exempted.  Croker  states 
that  these  eruptions  may  be  accompanied  by  oronasal  catarrh.  The 
difficulty,  in  diagnosia  may  be  increased  by  the  appearance  of  the  anti- 
pyrin eruption  following  catarrhal  symptoms,  such,  for  instance,  as  are 
"eficountered  in  influenza,  for  which,  the  drug  is  administered.  The  con- 
jtmctrvTtis,  photophobia,  hoarseness,  cough,  and  buccal  eruption  are  all 
absent.  Fever,  when  present,  is  slight  and  not  characteristic  of  measles. 
Furthermore,  the  normal  progression  of  the  measles  exanthem  from  the 


528 


MEASLES 


face  and  neck  gradually  downward  will  be  found  lacking.  The  eruption, 
moreover,  is  apt  to  be  non-elevated  and  exhibit  irregularities  as  to  dis- 
tribution. If  a  large  dose  of  antipyrin  has  been  taken  the  drug  can 
be  found  in  the  urine  by  testing  the  same  with  the  perchloride  of  iron. 
Quinine. — Quinine  gives  rise  not  infrequently  to  erythematous  erup- 
tions. Of  60  quinine  eruptions  analyzed  by  Morrow,  38  were  of  the 
erythematous  variety.  Most  of  these  are  of  the  scarlatiniform  type, 
but  some  resemble  measles.  The  rash  may  develop  after  the  admin- 
istration of  as  small  a  quantity  as  a  grain  or  even  a  fraction  of  a  grain 
of  the  drug.    The  idiosyncrasy  appears  to  be  most  frequently  observed 


m  women. 


Fig.  SS 


A  morbilliform  eiythema  somewliat  resembling  measles,  probably  due  to  intestinal 
autointoxication. 


The  eruption  may  be  generally  distributed  or  limited  to  certain  areas. 
It  sometimes  appears  first  on  the  face,  spreading  thence  downward 
over  the  trunk  and  limbs.  The  lesions  are  bright  or  dull  red  macules 
or  papules,  which  may  quite  strongly  resemble  the  measles  exanthem. 
Itching  is  apt  to  be  a  more  prominent  symptom  than  that  accompanying 
measles.  Desquamation  not  infrequently  follows.  In  some  cases 
febrile  symptoms  are  present  at  the  beginning;  there  may  be  a  fever 
of  101°  or  102°  F.,  with  headache,  nausea  or  vomiting,  and  weakness. 
Catarrhal  symptoms  are  absent. 

Eruptions  from  the  administration  of  chloral  are  less  common  than 
those  after  antipyrin  or  quinine.    Gee^  saw  two  cases  in  which  there  was 

1  Quoted  by  Crocker,  Diseases  of  the  Skin,  American  edition,  1903,  p.  483. 


77//';  /'/>'()(,' NOSIS  OF  Mh'ASIJ'JS  rj29 

a  dusky-red,  papulnr  eruption  surrounded  hy  ;i  more  difl'use  redness  of 
the  face  and  neck,  and  pateliy  or  mottled-re(J  sj^fjts  on  the  extremities, 
especially  about  the  articulations. 

The  absence  of  the  catarrhal  and  constitutional  manifestations  of 
measles  would  enable  one  to  exclude  this  infection. 

Coj'AHiA  and  CiiiiKHS.  — C!opaiba  and  cubebs  may  give  rise  to  scarla- 
tiniform  or  morbilliform  rashes.  The  former  (h-ug  usually  })roduces  an 
eruption  consisting  of  rose-red  colored,  slightly  raised  patches,  which 
may  be  discrete  or  blotchy  and  generalized  or  limited.  About  the  elbows 
and  knees  there  is  a  tendency  toward  confluen(;e  of  tjje  patches.  Itching 
is  apt  to  be  a  distressing  symptom.  The  erui)tion  may  develop  rapidly 
after  the  administration  of  the  drugs  or  only  after  some  days  have 
elapsed.  Most  of  the  eruptions  have  occurred  in  persons  who  were 
receiving  treatment  for  urethritis.  A  peculiar  and  disagreeable  balsamic 
odor  is  often  imparted  to  the  skin  when  copaiba  is  taken. 

All  of  the  drug  eruptions  are  apt  to  exhibit  irregularities  as  to  the 
manner,  rapidity,  distribution,  or  duration  of  the  eruption  which  will 
arouse  suspicion  as  to  its  nature;  furthermore,  the  prodromal  stage  of 
measles  with  its  characteristic  catarrhal  symptoms  is  wanting. 

Antitoxic  Sera. — Antitoxic  sera  occasionally  call  forth  eruptions 
which  are  measles-like  in  character.  Diphtheria  antitoxin  may  now 
and  then  give  rise  to  a  morbilliform  erythema,  although  much  more 
commonly  the  eruption  resembles  urticaria  or  exudative  erythema. 
Antitoxin  rashes  may  develop  at  any  time  from  three  days  to  three  weeks 
after  its  administration;  most  rashes,  however,  appear  from  eight  to 
fourteen  days  thereafter.  There  may  be  elevation  of  temperature 
with  joint  pains  and  occasionally  joint  swellings  accompanying  the 
eruption.  The  temperature  may  rise  suddenly  to  102°  F.  or  thereabouts, 
but  it  soon  falls.    Catarrhal  symptoms  are  invariably  absent. 

The  antistreptococcus  serum  and  antitetanic  serum  may,  on  rare 
occasions,  also  give  rise  to  morbilliform  eruptions. 

THE  PROGNOSIS  OF  MEASLES. 

It  appears  to  be  a  -difhcult  matter  to  dispel  from  the  minds  of  mothers 
the  idea  that  measles  is  a  trivial  disease.  When  it  is  stated,  according 
to  the  Twelfth  Census  Report,  that  measles  in  the  United  States,  in  the 
year  1900,  caused  12,866  deaths,  more-  than  twice  the  number  that 
re?MiEed"lfom  scarlatina,  it  is  evident  that  this  disease  is  not  essentially 
"beniOTTin  its  outcome.  The  above  statement  must  not  be  construed  to 
mean  that  measles  is  more  dangerous  than  scarlet  fever,  but  that,  attack- 
ing as  it  does  a  much  larger  percentage  of  humanity,  the  aggregate  loss 
of  life  is  greater. 

The  prognosis  of  measles  in  vigorous  and  well-nourished  children 
beyond  the  age  of  tw^o  or  three  years  is  extremely  favorable. 

The  factors  that  exert  an  important  influence  upon  the  prognosis 
are  the  age  of  the  patient,  his  previous  health,  and  the  nature  of  his 
surroundings.  Season  and  climate  are  thought  to  exercise  some  influence 
upon  the  disease  and  its  complications. 

34 


530 


MEASLES 


Age. — The  age  of  the  patient  is  the  most  important  factor  in  estimating 
the  degree  of  danger  attendant  upon  an  attack  of  measles.  During  the 
first  six  months  of  Kfe  infants  usually  resist  the  infection  of  measles 
altogether  or  take  it  in  feeble  form.  "With  this  exception,  children  under 
two  years  of  age  who  contract  measles  have  a  dangerous  disease  to 
contend  with.  Holt  states  that  the  average  mortality  from  measles 
during  this  period  is  not  far  from  20  per  cent. 

After  the  third  year  of  life  the  danger  rapidly  diminishes,  reaching 
a  minimum  after  the  age  of  five  has  been  passed. 

The  following  figures  of  Tripe^  indicate  the  relation  of  age  to  mor- 
tality. 

Mortality  of  Measles  in  England  from  1868  to  1872. — In  1000  fatal 
cases  the  age  of  the  patients  was: 


0-1  year     . 

.    200  cases. 

5-15 

years  . 

.    72  cases 

1-2  years   . 

.     376      " 

15-25 

"      . 

.      3      " 

2-3      "      . 

.     190      " 

25-45 

" 

.      4      " 

3-4      "      . 

.     101      " 

45-60 

"      . 

.     1  case. 

4-5      "      . 

.      53      " 

Over  65 

"      . 

.     0     " 

It  is  thus  seen  that  about  three-quarters  of  the  deaths  occurred  in 
children  under  three  years  of  age. 

Dawson  Williams  states  that  in  the  forty  years  from  1848  to  1887  there 
were  in  England  and  Wales  367,602  deaths  attributed  to  measles,  and 
of  this  number  335,874  occurred  in  children  under  five  years  of  age, 
leaving  only  31,728  to  distribute  among  other  ages. 

The  best  opportunity  of  judging  of  measles  susceptibility  and  fatality 
at  the  various  ages  is  afforded  in  studying  an  entire  epidemic  in  a 
locality.  Dr.  Theodore  Thomson^  presents  such  a  table  of  an  epidemic 
in  an  English  town,  from  which  the  following  data  are  abstracted : 

Measles 
Age.  Population,    attacks.     Deaths.      Mortality  rate. 

0-1  year 
1-2  years 
2-3  " 
3-4  " 
4-5  " 
5-10  " 
10  years  and  upward 

At  all  ages     . 

This  table  indicates  the  lesser  susceptibility  of  infants  under  one  year 
of  age  and  also  the  lower  death  rate  as  compared  with  the  next  two 
years. 

During  youth  and  early  adult  life  the  mortality  from  measles  is  low. 
Patients  who  are  advanced  in  years  not  infrequently  succumb  to  the 
disease.  This  is  shown  in  Panum's^  report  of  the  Faroe  Islands  epidemic 
of  1845. 


.       1155 

166 

16 

6.9  per  ct 

974 

233 

46 

23.6      " 

.       1028 

354 

36 

J7.5      " 

.        1000 

324 

16 

8.0      " 

951 

324 

5 

2.6      " 

.       4530 

560 

6 

0.7      " 

.    25,968 

39 

0 

0.0      " 

.    35,606 

1031 

125 

1.7      " 

1  Quoted  in  Jahrbuch  f.  Kinder.,  vol.  ix.  p.  412. 
»  Loc.  cit.,p.  287. 


2  Quoted  by  Williams,  loc.  cit. 


TIIM  PROGNOSIS  OF  MEASLI'JS  531 

Mortality  Rate  of  Mrahmos  in  tiik  Farok  Ihi>ani)8  in  1845, 

Age.  Mortality  rate.  Ak';.  Mortality  rate. 

Under  1  year         .    30.0  per  ct.  40-60  years     .        .      2.8  per  ct. 


1-10  years 
10-20       " 
20-80       " 
80-40       " 


0.6  "  60-60 

0.4  "  60-70 

0.75  "  70-80 

2.1  "  80-100 


4.5 

7.8 
Kll 
26.1 


These  figures  are  unusual  in  that  such  a  great  mortality  is  shown  in 
infants  under  one  year  of  age  and  such  a  remarkably  small  dfath  rate 
in  those  between  one  and  three  years.  The  increasing  mortality  in 
patients  past  the  age  of  forty  is  well  illustrated.  In  an  extremely  mild 
epidemic  in  the  Faroe  Islands  in  1875,  Hoff  states  that  while  only  8  out 
of  1123  cases  ended  fatally,  5  of  these  were  vigorous  adults  between  the 
age  of  twenty  and  thirty  years.  This  must  be  regarded  as  an  exceptional 
circumstance. 

Institutional  Epidemics. — It  will  be  found  convenient  to  discuss  here 
the  influence  of  institutional  environment  upon  the  mortality  rate  of 
measles.  It  is  a  generally  recognized  fact  that  measles  occurring  among 
children  in  homes,  nurseries,  asylums,  hospitals,  etc.,  is  much  more 
fatal  than  when  it  develops  among  children  in  their  private  homes. 
Indeed,  measles  is  regarded  as  the  scourge  of  children's  institutions,  for 
it  decimates  the  little  patients  like  a  plague.  There  are  a  number  of 
reasons  for  this.  Such  children  usually  come  from  poor  stock  and 
therefore  lack  power  of  resistance.  The  children  in  foundling  a.sylums, 
nurseries,  and  hospitals  are  of  a  tender  age,  which  in  itself  accounts  for 
a  high  mortality.  They  are  usually  frail  and  in  poor  health  or  already 
perhaps  suffering  from  an  acute  or  a  chronic  disease.  The  atmosphere 
is  often  vitiated  and  infected  and  the  liability  to  such  complications 
as  pneumonia  and  diphtheria  is  increased. 

The  mortality  in  such  institutions  as  have  been  mentioned  is  often 
frightful.  Holt  speaks  of  an  epidemic  in  1892  in  the  Nursery  and 
Child's  Hospital  in  New  York  in  which  there  were  143  cases  with  a  death 
rate  of  35  per  cent.  An  epidemic  in  the  same  institution  in  1895  had 
an  almost  identical  mortality  rate. 

Comby  gives  the  following  statistics  showing  the  death  rate  in  some 
of  the  Paris  hospitals: 

Hospice  des  Enfants  Assistes. 

Year.  Cases. 

1882  .        . 280 

1883 268 

1884 328 

1885  .        .    ~ 370 

1886 .i29 

Total  in  five  years        ....  1575  728  46.22 

The  death  rate,  therefore,  during  these  five  years  was  nearly  50  per 
cent.,  a  truly  appalling  figure. 

In  I'Hopital  des  Enfants  Malades,  for  a  period  of  seven  years  from 
1882  to  1888,  there  were  treated  2585  cases  of  measles,  with  a  death  rate 
of  40.15  per  cent. 


Deaths. 

Percentage 

128 

45.0 

128 

47.0 

187 

57.0 

147 

46.0 

138 

42.0 

532  MEASLES 

In  I'Hopital  Trousseau,  from  1882  to  1886,  there  were  907  cases  of 
measles,  with  a  mortaHty  rate  of  25.02  per  cent.  From  1890  to  1894 
there  were  2248  cases  treated  in  special  isolation  pavilions,  but  the 
mortality  rate  still  remained  high — 28  per  cent. 

It  is  difficult ,  to  obtain  accurate  information  as  to  the  death  rate  of 
measles  in  private  practice,  for  while  the  deaths  are  recorded  the  number 
of  attacks  is  usually  not  known.  The  fact  is  well  established,  however, 
that  the  fatality  is  very  much  less  in  this  class  of  patients. 

Sex  does  not  influence  the  mortality  from  measles.  Of  12,866  persons 
who  died  of  measles  in  the  United  States  in  1900,  6231  were  males  and 
6635  were  females.  The  frequency  of  measles  in  pregnant  women  is 
not  sufficient  to  disturb  the  balance.  Moreover,  the  infection  of  measles 
superadded  to  pregnancy  is  not  as  serious  as  some  of  the  other  exan- 
thematous  diseases,  notably  scarlet  fever  and  smallpox. 

Previous  Health  of  the  Patient.^ — Measles  as  a  primary  disease  is 
very  much  less  serious  than  when  it  becomes  engrafted  upon  some 
other  acute  or  chronic  affection.  Secondary  measles  is  an  extremely 
fatal  disease;  occurring  in  patients  who  are  convalescing  from  diphtheria, 
scarlet  fever,  whooping-cough,  etc.,  the  danger  is  greatly  enhanced. 

The  mortality  is  also  high  when  measles  attacks  children  who  are 
badly  nourished  and  who  are  scrofulous  or  anaemic.  In  those  with 
enlarged  glands  and  a  tendency  to  pulmonary  tuberculosis  an  attack 
of  measles  may  be  sufficient  to  stimulate  this  process  into  activity. 
The  unfavorable  influence  of  hardship  and  privation  is  exemplified  in 
camp  measles,  which  is  nearly  always  characterized  by  a  high  death  rate. 

Character  of  Epidemic. — The  mortality  of  measles  depends  much 
upon  the  severity  of  the  prevailing  epidemic.  At  times  the  type  of 
measles  is  unusually  mild  and  the  death  rate  extremely  low;  some 
epidemics,  on  the  other  hand,  are  characterized  by  special  malignancy. 
Fatal  epidemics  of  measles  may  cause  a  high  mortality,  not  only  through 
an  excessive  development  of  the  regular  symptoms  of  the  disease,  but 
through  the  frequency  of  serious  complications.  Indeed,  it  is  the 
frequency  or  rarity  of  bronchopneumonia  during  an  epidemic  that 
determines  in  a  large  measure  its  malignancy. 

The  average  mortality  of  measles  is  from  4  to  6  per  cent.  The 
deaths  may  in  some  epidemics  not  exceed  1  or  2  per  cent.,  while  in 
others  they  may  reach  the  murderous  figures  of  20  or  30  per  cent. 

In  1856,  in  Lippe,  Hungary,  a  malignant  epidemic  prevailed,  destroy- 
ing the  lives  of  50  per  cent,  of  those  attacked.  Measles  again  occurred 
in  this  locality  thirteen  years  later,  with  a  mortality  of  3  per  cent. 

Faber  states  that  at  Schorndorf  in  the  epidemic  of  1827-28  there  were 
2100  cases  of  measles,  with  a  mortality  of  only  1.8  per  cent.  Among 
other  mild  epidemics  may  be  mentioned  the  following,  quoted  by  Thomas : 
According  to  Ranke  the  mortality  in  four  epidemics  in  Munich  varied 
from  0.7  to  2,7  per  cent.  Kostlin  reports  a  mortality  in  Stuttgart  of 
1,8  per  cent,  for  the  years  1852  to  1865, 

Among  severe  epidemics  (according  to  Thomas)  may  be  mentioned 
the  fatal  epidemic  in  the  district  of  Zolkiew  in  1840;  Seidl  mentions  that 


Cases. 

JJealhH. 

I'ercentagc. 

582 

139 

27.7 

45 

13 

28.8 

125 

40 

32.0 

457 

1G8 

36.7 

TUIi  l'J{()aNOS/S  O/''  M/'JASLh'S  533 

out  of  1519  cases  there  were  196  deaths,  a  mortality  of  almost  13  per 
cent.    Accord irif^  to  Schiiz  measles  f)revailed  at  Nagold  with  a  mortality 
of  10  per  cent.    Small  (!f)idemics  in  certain  localities  have  been  accom- 
{)anie(l  by  even  hipjher  mortality. 
Colin^  gives  the  following  figures: 

Year.  J.ocalities. 

1861  .       .       .       .       .    Ruelle 

1864 Arras 

1860 Val-de-Grace 

1870 BicCtre 

A  mahgnant  e})idemic  raged  in  Sunderland,  England,  in  1885. 
Harris^  states  that  of  1316  cases  384  died,  giving  a  mortality  of  20 
per  cent. 

Measles  often  manifests  unusual  malignancy  on  reaching  a  virgin 
soil,  particularly  among  savage  tribes.  It  is  stated  on  the  authority 
of  d'Alves  that  30,000  Indians  perished  from  mea.sles  along  the  banks 
of  the  Amazon  River  in  1749-50.  In  1806,  in  Madaga.scar,  5000  persons 
are  said  to  have  succumbed  to  the  disease  in  a  single  month.  Among 
the  Fiji  Islanders  measles  has  exhibited  as  high  a  death  rate  as  30  per 
cent.;  the  disease  has,  as  might  be  expected,  inspired  a  wholesome 
dread  among  the  natives. 

Season  and  Climate. — Inasmuch  as  the  mortality  of  measles  is  greatly 
influenced  by  the  frequency  of  pneumonia,  one  would  naturally  suppose 
that  this  complication  would  be  more  common  and  the  death  rate 
consequently  higher  in  the  cold  and  inclement  seasons  of  the  year. 
But  such  an  assumption  is  not  entirely  borne  out  by  facts.  The  figures 
which  are  published  by  writers  as  to  the  influence  of  season  on  measles 
mortality  lack  uniformity  and  preclude  the  possiblity  of  drawing  there- 
from satisfactory  conclusions. 

Deaths  from  Measles  in  England  and  Wales  by  Quarterly  Periods. 


Quarterly  Periods. 

1837. 

1838. 

1839. 

1840 

January,  February,  and  March 

2022 

2074 

2836 

April,  May,  June 

1512 

3204 

2641 

July,  August,  September    . 

.    2362 

1037 

2767 

1739 

October,  November,  December 

.     2392 

1943 

2892 

2110 

Total  deaths    .... 

.     4754 

6514 

10,937 

9326 

Gregory,  who  publishes  the  above  table,  remarks  that  "season  would 
appear  to  have  less  influence  on  the  mortality  of  measles  than  might 
have  been  anticipated." 

According  to  Karajan,'  measles  occurring  in  lower  Austria  in  1862, 
during  the  presumably  unfavorable  cool  months,  was  attended  with  a 
mortality  of  only  2.29  per  cent.,  whereas  the  disease  prevailed  in  the 
same  district  during  the  following  summer  with  a  mortality  which 
reached  6.29  per  cent. 

Passow*  states  that  the  fatal  cases  of  measles  in  Berlin  from  1863  to 

1  Quoted  by  Comby.  -  Lancet,  April  30, 1887,  p.  970. 

3  Quoted  by  Thomas,  *  Quoted  by  Thomas. 


534  MEASLES 

1867  were  distributed  as  follows:  winter,  41.4  per  cent.;  autumn,  33.4 
per  cent.;  summer,  13.3  per  cent.;  spring,  11.9  per  cent. 

In  the  United  States  the  most  fatal  season  from  measles  would  appear 
to  be  the  late  winter  and  early  spring  months. 

In  the  city  of  New  York,  during  a  period  of  fifteen  years  from  1830 
to  1844,  in  which  time  2104  deaths  from  measles  occurred,  the  seasonal 
mortality  was  as  follows: 

January,  February,  March 610  deaths. 

April,  May,  June 574        " 

July,  August,  September 536       " 

October,  November,  December 384       " 

It  is  thus  seen  that  the  highest  mortality  was  in  the  first  three  months 
of  the  year  and  the  lowest  in  the  last  three. 

The  United  States  Census  Report  for  the  year  1900  shows  that  the 
greatest  number  of  deaths  from  measles  occurred  during  the  months 
of  February,  March,  April,  and  May. 

Comparative  Pboportion  of  Deaths  in  Each  Month  pee  1000  Deaths 
IN  the  United  States  for  the  Year  J  900. 


January    . 

.      95.0 

July     . 

.    48.5 

February  . 

.    150.1 

August 

.    43.6 

March 

.    176.0 

September  . 

.    34.7 

April . 

.    146.8 

October 

.    25.5 

May   . 

.    130.3 

November  . 

.    34.6 

June  . 

.      66.4 

December  . 

.    48.5 

Climate  doubtless  has  some  influence  upon  the  mortality  of  measles. 
Gregory  says  that  "in  hot  countries  measles  is  not  viewed  with  alarm, 
evidently  from  the  absence  of  thoracic  complications."  It  occurs  to  us, 
however,  that  the  greater  tendency  to  intestinal  complications  might 
counterbalance  the  advantage.  The  mortality  of  measles  varies  in 
different  localities.  It  is,  as  would  be  expected,  greater  in  large  cities, 
where  there  are  greater  numbers  of  overcrowded  poor  than  in  rural 
districts.  Even  in  large  capitals  a  considerable  discrepancy  in  the 
mortality  exists. 

Thus  the  mortality  from  measles  is  much  greater  in  London  than  in 
Berlin;  this  is  strikingly  shown  by  the  following  figures: 

Measles  Deaths  per  10,000  of  Population. 


Year. 

Paris. 

London. 

Berlin. 

Vienna 

1880  to  1889      . 

.    52 

60 

30 

00 

1890  "  1894      . 

.    41 

77 

20 

70 

1895  .... 

.    26 

59 

17 

49 

From  a  consideration  of  the  above  remarks  it  will  be  seen  that  many 
factors  influence  the  prognosis;  chief  among  these,  however,  are  the 
age  of  the  patient,  his  general  health  and  environment,  and  the  severity 
of  the  epidemic.  Those  epidemics  which  furnish  the  largest  number  of 
anomalous  cases  and  the  greatest  percentage  of  serious  complications 
are  most  to  be  feared. 
,B,,«*a***«'^«s?iBronchopneumonia  causes  nine  .oiil^  ten  deaths  from  measles.  It 
is  the  principal  danger  to  which  measles  patients  are  liable.    Holt  states 


THE  TREAT  Ml':  NT  OF  Mf'JASLES  535 

that  of  51  fatal  cases  of  measles  45  were  due  to  bronchopneumonia, 
4  succumbed  to  ileocolitis,  and  2  to  membranous  laryngitis. 

Among  36  deaths  observed  by  Northrup,'  in  an  epidemic  in  the  New 
York  Foundling  Hospital,  bronchopneumonia  was  found  post-mortem 
in  31  cases. 

Favorable  Symptoms. — The  symptoms  of  measles  are  favorable  when 
the  initial  temperature  is  moderate,  not  exceeding  103°  F.,  and  when  it 
remits  in  the  pre-eruptive  stage;  when  the  temperature  declines  witli  the 
beginning  fading  of  the  eruption;  when  the  eruption  is  discrete,  well 
developed,  and  of  bright  color;  when  it  appears  about  the  fourth  day 
and  progresses  gradually  over  the  body;  when  the  catarrhal  symptoms 
are  of  moderate  intensity;  when  complications  are  absent. 

Unfavorable  Symptoms. — It  is  unfavorable  for  the  initial  temperature 
to  be  very  high  (above  103°  F.),  or  for  it  to  persist  high  or  increase  be- 
fore the  eruption  appears.  It  is  ominous  for  the  fever  to  remain  high 
after  the  rash  fades,  for  this  usually  portends  pulmonary  complications. 
It  is  unfavorable  for  the  eruption  to  appear  late,  for  it  to  be  unusually 
profuse  or  confluent  or,  on  the  other  hand,  sparse,  pale,  and  livid.  A 
partial  or  poorly  developed  eruption  with  high  fever  is  a  bad  sign. 
Hemorrhagic  eruptions  are  usually  of  evil  portent,  especially  when 
accompanied  by  hemorrhages  from  the  mucous  membranes.  Sudden 
and  premature  recession  of  the  eruption  indicates  cardiac  weakness. 
Convulsions  or  other  marked  nervous  symptoms,  severe  diarrhoea, 
persistent  hoarseness,  with  difficulty  in  breathing  or  continued  high 
temperature,  indicate  serious  complications. 


THE  TREATMENT  OF  MEASLES. 

In  discussing  the  treatment  of  measles  it  must  be  remembered  that 
we  are  dealing  with  a  disease  which  is  far  from  trifling  in  its  nature — 
one  whose  aggregate  annual  mortality  exceeds,  at  the  present  day,  that 
of  any  eruptive  disease,  not  excluding  smallpox.  In  1889  there  were 
14,732  deaths  from  measles  in  England  and  Wales;  in  1900  the  mortality 
from  measles  in  the  United  States  was  12,866.  These  figures  are  not 
far  from  representing  the  average  annual  mortality  in  these  countries. 

We  have  no  doubt  that  at  least  100,000  persons,  chiefly  children, 
perish  throughout  the  world  each  year  from  measles. 

The  subject  is,  therefore,  of  sufficient  importance  to  warrant  a  full 
consideration  of  the  prophylactic  treatment  of  measles  and  its  relation 
to  the  community  at  large. 

Prophylaxis — That  the  spread  of  measles  can  be  greatly  lessened  by 
proper  sanitary  measures  has  been  shown  by  the  results  accomplished 
by  the  Michigan  State  Board  of  Health.^  Public  health  measures  may 
be  considered  under  the  headings  of  (1)  Notification,  (2)  Isolation, 
and  (3)  Disinfection. 

1  Medical  News,  1897,  vol.  Ixxi.  p.  817. 

"  Baker,  Reports  and  leaflets  on  the  Prevention  and  Restriction  of  the  Infectious  Diseases,  etc.,  1900. 


536  MEASLES 

Notification. — There  is  considerable  difference  of  opinion  as  to  the 
benefits  derived  from  making  measles  a  notifiable  disease.  Bearing  in 
mind  the  fact  that  measles  in  many  countries  kills  more  children  than 
scarlet  fever  and  diphtheria  combined,  there  can  be  but  one  point 
of  view  as  to  the  desirability  of  checking  its  ravages.  It  is  only  through 
a  knowledge  of  the  distribution  and  extent  of  measles  that  health 
authorities  are  enabled  to  direct  measures  against  its  spread.  How 
effective  such  measures  are  offers  latitude  for  discussion. 

The  chief  difficulty  arises  from  the  early  communicability  of  the 
disease.  As  soon  as  a  patient  manifests  the  first  symptom  of  measles, 
those  who  have  been  exposed  and  are  susceptible  are  almost  sure  to 
contract  the  disease,  and  isolation,  as  far  as  these  persons  are  concerned, 
is  too  late.  Infection  may  at  times  take  place  even  before  the  patients 
sicken,  as  is  illustrated  in  the  following  cases  mentioned  by  Dr.  Fenton, 
Medical  Officer  of  Health  for  Coventry,  England:^  "Thirteen  children 
attended  a  dancing  class  one  afternoon,  including  3  of  my  own 
and  2  of  a  friend,  who  had  just  arrived  in  the  district,  and  who 
had  been  exposed  to  the  infection  of  measles  before  arriving.  These 
2  children  came  to  my  house  and  spent  the  evening  in  my  presence. 
There  was  nothing  to  attract  my  attention  to  their  condition,  and, 
indeed,  so  well  were  they  that  they  had  walked  six  miles  in  the  morning, 
had  danced  in  the  afternoon,  and  walked  home  about  one  mile  at  night. 
Next  day  they  both  sickened  and  developed  measles.  Of  the  remaining 
11  children  2  were  presumably  immune,  having  previously  suffered 
from  measles,  but  the  whole  of  the  9  developed  measles  during  the 
following  fourteen  days."  This  incident  is  evidence  of  the  early  con- 
tagiousness of  measles  and  the  difficulties  that  are  encountered  in  pre- 
venting its  dissemination.  But  much  can  be  accomplished  in  prevent- 
ing unnecessary  exposure  to  the  disease,  and  to  this  end  notification  is 
eminently  desirable,  if  not  essential. 

The  education  of  the  masses  is  a  matter  of  paramount  importance  in 
stamping  out  measles.  Mothers  must  be  taught  that  measles  is  a 
serious  disease — a  disease  that  destroys  many  lives,  and  that  exposure 
to  it  must  be  avoided.  Even  among  the  intelligent  middle  classes  there 
is  a  tendency  to  regard  escape  from  measles  as  futile,  and  mothers  make 
little  effort  to  avoid  an  infection  which  is  regarded  after  all  as  inevitable. 
"The  baby  might  as  well  take  measles  now  as  later"  is  the  dangerous 
and  erroneous  view  often  expressed. 

Mothers  should  be  made  to  realize  the  fact  that  measles  kills  more 
children  under  two  years  of  age  than  any  other  disease  save  possibly 
whooping-cough,  and  that  about  80  per  cent,  of  all  deaths  from  measles 
are  in  children  under  five  years  of  age.  If  children  be  safely  guarded 
through  this  period  of  their  life  without  contracting  measles  an  enormous 
saving  of  life  would  result. 

It  is  a  good  plan  to  send  circulars  of  instruction  to  all  households 
which  are  in  the  neighborhood  of  an  infected  domicile. 

1  Quoted  by  Dawsbn  Williams. 


THE  TUKATMKNT  OF  MEASLES  587 

Isolation. — When  a  child  is  stricken  with  measles  in  a  househokl  in 
which  there  are  other  susceptible  (children  it  should  be  promptly  isolated. 
The  isolation  should  not  be  delayed  until  the  dia^niosis  is  confirmed 
by  the  ap])earance  of  the  eruption,  but  uj)Om  the  first  suspicion  that  the 
disease  mi^ht  be  measles. 

In  selecting  an  apartment  for  the  patient  such  a  room  or,  preferably, 
a  suite  of  rooms  is  to  be  chosen  as  can  be  most  effectually  separated 
from  the  rest  of  the  house.  It  will  usually  be  found  that  the  uppermost 
rooms  of  the  house  are  most  suitable  and  available.  In  choosing  the 
apartment  care  should  be  given  to  the  facilities  for  ventilation.  Admir- 
able ventilation  is  furnished  by  an  open  fireplace  in  which  fire  is  kept 
constantly  burning,  but  such  a  convenience  will  usually  be  found 
wanting.  The  most  common  method  of  securing  the  necessary  change 
of  air  is  from  a  window  sufficiently  removed  from  the  sick-bed  to  avoid 
direct  currents  of  air  striking  the  patient.  A  rather  safer  method, 
particularly  in  such  a  disease  as  measles,  is  to  ventilate  through  the 
adjoining  room,  as  suggested  by  J.  P.  C.  Griffith.^  The  windows  of  this 
room  may  be  kept  open  and  the  fresh  air  permitted  to  enter  the  sick- 
room through  the  communicating  door,  which  is  opened  for  this  purpose 
from  time  to  time.  As  this  room  also  forms  the  channel  of  communica- 
tion with  the  remainder  of  the  house,  the  opening  of  the  windows  will 
tend  to  dilute  or  dissipate  the  infection. 

All  unnecessary  articles  of  furniture,  such  as  drapery,  carpets,  and 
upholstery  should  be  removed.  The  spaces  around  doors  communicating 
with  parts  of  the  house  to  be  protected  should  be  sealed  by  pasting 
strips  of  wrapping  paper  over  them.  The  contagium  of  measles  is  so 
diffusible  that  unless  this  precaution  is  taken  the  infection  will  travel 
beyond  the  sick-chamber.  Over  the  door  leading  into  the  corridor 
should  be  suspended  a  sheet  which  is  kept  moist  with  diluted  Labar- 
raque's  solution,  carbolic  acid  (5  per  cent.),  or  a  1 :  1000  solution  of 
corrosive  sublimate. 

The  woodwork  and  the  floors  of  the  apartment  should  be  kept  clean 
by  mopping  with  cloths  saturated  wdth  antiseptic  solutions.  Owing  to 
the  liability  to  pulmonary  complications  in  measles,  sweeping  of  the 
sick-room  should  be  assiduously  avoided. 

The  nurse  or  attendant  should  not  leave  the  sick-apartments  save 
after  change  of  clothing  and  thorough  ablution.  If  the  mother  wait 
upon  her  child  she  should  devote  her  time  exclusively  to  the  patient, 
and  not  come  in  contact  with  susceptible  members  of  the  family.  Such 
garments  should  be  worn  by  the  nurse  or  mother  as  can  be  readily 
washed. 

All  articles  coming  in  contact  with  the  patient,  such  as  dishes,  bed 
and  body  linen,  etc.,  should  be  disinfected  in  the  adjoining  room,  where 
solutions  for  this  purpose  should  be  kept  on  hand.  A  5  per  cent,  solution 
of  carbolic  acid  will  suffice  for  this  purpose,  although  for  the  dishes 
boiling  water  is  to  be  preferred. 

1  Hare's  System  of  Practical  Therapeutics,  p.  132. 


538  MEASLES 

It  is  a  difficult  matter  to  state  just  how  long  measles  patients  should 
be  isolated.  Unlike  scarlet  fever  the  disease  is  most  contagious  early, 
and  the  period  of  infectiousness  is  short  lived.  Most  pediatricians  are 
of  the  opinion  that  the  period  of  isolation  should  be  in  all  from  two  to 
three  weeks.  In  uncomplicated  cases  two  weeks  are  probably  sufficient 
if  desquamation  has  ceased.  Whether  or  not  the  desquamation  of 
measles  is  infectious  is  an  undetermined  problem,  with  plenty  of  advo- 
cates to  champion  each  side  of  the  question.  It  is  proper  to  state  that 
certain  physicians  who  have  had  unusual  opportunities  of  judging,  such 
as  Hoff,  Peterson,  and  Comby,^  deny  the  infectiousness  of  the  stage  of 
desquamation.  The  last-named  observer  says:  "We  know  to-day  that 
measles  ceases  to  be  contagious  after  the  eruption."  In  institutions 
where  so  much  depends  on  effective  isolation,  patients  should  be  sepa- 
rated for  the  full  period. 

Utility  or  Futility  of  Isolation. — There  are  many  physicians 
who  deem  isolation  in  private  residences  futile  and,  therefore,  do  not 
advise  it.  It  must  be  admitted  that  when  measles  appears  in  a  child 
to  whom  susceptible  children  have  been  freely  exposed,  isolation  is  too 
late.  If,  however,  patients  are  isolated  upon  the  first  suspicion  of 
measles,  a  certain  small  proportion  of  the  exposed  will  probably  escape, 
particularly  babies,  whose  susceptibility  is  slight  and  whom  it  is  par- 
ticularly important  to  protect.  Where  such  young  infants  can  be  sent 
to  another  household  this  course  is  eminently  desirable,  provided  no 
susceptible  children  be  there  resident.  It  is  unjustifiable  to  send  exposed 
children  to  a  home  where  unprotected  persons  reside,  for  these  in  turn 
would  be  exposed  upon  the  former  falling  ill. 

It  is,  of  course,  recognized  that  the  method  of  isolation  above  outlined 
could  not  be  carried  out  among  the  poor  nor  in  families  living  in  re- 
stricted quarters.  Moreover,  there  are  many  people  who  would  refuse 
to  go  to  such  inconvenience  and  expense,  with  the  knowledge  that  the 
benefits  to  be  derived  are  doubtful.  We  feel  that  when  measles  breaks 
out  in  a  household  in  which  unprotected  persons,  particularly  children 
under  three  years  of  age,  live,  the  proper  course  to  pursue  is  to  isolate 
the  patient.    Such  a  procedure  would,  in  the  long  run,  save  lives. 

When  measles  develops  in  an  institution  for  children,  the  patient 
should  be  immediately  isolated.  No  new  admissions  should  be  per- 
mitted save  to  quarters  which  are  completely  separated  and  protected 
from  the  infected  apartments.  The  exposed  children  should  be  kept 
under  close  surveillance  until  the  extreme  limits  of  the  period  of  incu- 
bation have  been  passed. 

Disinfection. — The  germs  of  measles  have  comparatively  little  tenacity 
to  life  outside  of  the  human  body.  It  is  unusual  for  the  disease  to  be 
carried  by  infected  articles  or  third  persons.  We  do  not  subscribe, 
however,  to  the  positive  statements  made  by  some  physicians  that  the 
disease  is  never  communicated  in  this  manner.  In  hospitals  and  other 
institutions  for  children  wards  should  invariably  be  disinfected  after 

1  Loc,  cit.,  p,  200, 


THE  TREATMENT  OF  MEASLES  539 

measles  has  broken  out;  in  private  households  tlionju^li  cleansing  and 
subsequent  airing  nifiy  tjike  tlu;  })la(;e  of  the  more  rigid  measures  of 
disinfection  eni[)loyc(i  in  otlutr  infectious  (h'seases. 

General  Management  of  the  Disease. — Measles  runs  its  course  in  a 
definite  period  of  time  like  other  self-hmited  affections,  and  tends  in 
uncomplicated  cases  to  recovery.  No  know^n  drug  is  able  to  abridge 
or  modify  the  course  of  the  disease.  The  therapeutic  indications, 
therefore,  are:  (1)  to  mitigate  or  control  excessively  developed  symptoms 
and  (2)  to  treat  or,  preferably,  prevent  complications. 

The  temperature  of  the  sick-room  should  be  maintained  in  the 
neighborhood  of  70°  F.,  particularly  during  the  cold  months  of  the  year. 
It  is  important  that  the  temperature  l:)e  kept  uniform  and  not  be  allowed 
to  fall  during  the  hours  of  the  night.  While  it  is  desira})le  to  avoid 
direct  draughts  upon  the  patient,  it  is  equally  essential  to  keep  the 
room  well  ventilated  and  the  air  pure.  Owing  to  the  irritating  influence 
of  dry  air  and  the  increased  liability  to  dissemination  of  dust  in  such 
an  atmosphere,  it  will  be  found  advantageous  to  moisten  the  air  by 
one  method  or  another.  A  pan  of  water  may  be  heated  over  an  alcohol 
lamp  or  the  old-fashioned  kettle  of  steaming  water  may  be  brought 
into  the  room.  This  use  of  steam  is  even  more  important  when  a 
severe  catarrhal  laryngitis  or  bronchitis  is  present.  Under  such  circum- 
stances aromatic  and  sedative  medicaments,  such  as  the  compound 
tincture  of  benzoin  may  be  volatilized  by  being  placed  upon  the  surface 
of  the  steaming  water. 

The  habit,  fortunately  obsolete  for  the  most  part  now,  of  bundling 
up  measles  patients  with  an  excess  of  bed-clothes  is  to  be  deprecated. 

Mothers  should  be  instructed  that  the  guide  in  this  matter  is  the 
comfort  of  the  patient.  Sydenham  proved  several  centuries  ago  that 
the  "sweating  regimen"  was  out  of  place  with  a  feverish  patient.  In 
changing  the  bed-linen  of  patients  in  the  winter  months  it  is  advisable 
to  warm  the  sheets  before  they  come  in  contact  with  the  patient. 

It  will  be  found  necessary  to  protect  the  eyes  of  measles  patients 
against  too  strong  rays  of  light.  It  should  be  remembered,  however, 
that  it  is  not  necessary  to  make  a  room  absolutely  dark  in  order  to 
accomplish  this  purpose.  Just  sufficient  light  should  be  excluded  to 
make  the  patient  comfortable.  The  complete  shutting  out  of  daylight 
is  not  only  depressing,  but  the  air  is  robbed  of  the  purifying  and  germ- 
destroying  influence  of  the  sun's  rays. 

Patients  with  measles  may  be  sponged  daily  with  tepid  water.  The 
old-time  prejudice  against  the  use  of  water  in  the  eruptive  fevers  is  still 
harbored  by  some  oversolicitous  mothers,  but  is  scouted  by  physicians 
of  experience. 

In  order  to  avoid  complications  which  arise  from  the  catarrhal 
inflammation  of  the  nose,  mouth,  and  conjunctiva,  it  is  well  to  employ 
the  following  'preventive  measures  as  a  routine.  The  mouth  should  be 
washed  several  times  a  day  with  a  solution  of  boric  acid  to  which  a 
little  glycerin  and  a  few  drops  of  oil  of  wintergreen  may  be  added,  or 
instead  some  other  mild  antiseptic  w^ash  may  be  employed.     By  this 


540  MEASLES 

precautionary  measure  the  liability  to  ulcerative  stomatitis,  a  by  no 
means  rare  occurrence,  is  lessened.  Williams  regards  the  use  of  anti- 
septic mouth  washes  as  important,  because  "it  has  been  shown  that  the 
microbes  associated  with  bronchopneumonia  are  present  in  the  mouth 
in  more  than  half  the  cases  of  measles." 

The  nares  should  be  irrigated  every  few  hours  with  a  decinormal 
saline  solution.  Care  should  be  taken  that  the  syringe  is  gently  manip- 
ulated and  the  forcible  projection  of  fluid  into  the  nose  avoided. 

Comby  prefers  spraying  of  the  nose,  mouth,  and  throat  with  a  steam- 
atomizer.  He  state's  that  Siredey  obtained  excellent  results  by  this 
method  at  I'Hopital  d' Aubervilliers ;  before  this  treatment  was  used 
50  cases  of  measles  gave  23  complications  (46  per  cent.);  since  the 
employment  of  the  spray  53  cases  have  only  furnished  7  complications 
(13  per  cent.).  The  genitalia,  particularly  in  girls,  should  be  kept 
scrupulously  clean  owing  to  the  vulnerability  of  these  parts  to  gangrene 
involvement.  In  addition  to  the  use  of  soap  and  water  a  weak  solution 
of  bichloride  of  mercury  or  a  saturated  solution  of  boric  acid  may  be 
employed. 

Measles  patients  should  always  be  confined  to  bed  for  the  entire  febrile 
period  of  the  disease;  in  severe  cases  the  patient  should  not  be  allowed 
to  leave  bed  until  a  week  or  ten  days  after  the  termination  of  fever. 
During  the  cold  and  rainy  seasons  this  precaution  should  be  carefully 
observed.  During  the  balmy  days  of  late  spring  or  summer  one  need 
not  adhere  so  rigidly  to  this  rule.  It  is  difficult  to  keep  very  young,  rest- 
less children  constantly  in  their  cribs;  where  care  is  exercised  as  to  the 
equability  of  the  temperature  in  the  room  and  to  the  clothing  of  the  child, 
it  is  permissible  to  gratify  its  desire  to  be  taken  up  in  one's  arms.  Season 
and  climate  will  influence  the  duration  of  the  sojourn  in-doors.  Ordi- 
narily the  patient  should  not  go  out  for  ten  days  to  two  weeks  after  the 
subsidence  of  fever;  this  period  should  be  increased  in  cold,  wintry 
weather,  and  abbreviated  during  a  warm  and  dry  spell. 

Diet. — For  children,  milk,  preferably  diluted  with  barley-water,  is 
the  best  diet.  This  not  only  constitutes  the  most  assimilable  and 
nourishing  food,  but  helps  to  assuage  the  thirst  and  acts  on  the  kidneys. 
When  the  temperature  is  high  the  milk  may  be  taken  cool  and  will  be 
found  to  be  most  acceptable  to  the  patient.  Where  it  is  distasteful  to 
a  child  it  may  often  be  rendered  more  palatable  by  flavoring  it  with 
a  little  extract  of  vanilla.  As  measles  is  a  disease  of  short  duration  it  is 
not  essential  to  force  nourishment  upon  the  patients  as  in  more  pro- 
tracted affections,  such  as  typhoid  fever. 

It  will  be  found  that  when  the  temperature  is  high,  children  will  want 
nothing  but  cool  milk;  later  there  will  be  a  desire  for  a  more  varied 
dietary.  As  the  fever  declines  there  is  no  objection  to  the  use  of  junket, 
farina,  milk-toast,  broths,  arrowroot,  rice,  custard,  strained  oatmeal, 
soft-boiled  eggs.  It  will  be  well  to  avoid  those  cereals  which,  by  reason 
of  their  husk,  are  apt  to  excite  diarrhoea. 

I  For  the  relief  of  thirst,  apart  from  the  use  of  cool  milk,  the  patient 
may  partake  freely  of  water,  provided  it  is  not  iced.    In  older  children 


77//';  TIINATMI'INT  OF  MJ'JASLKS  o41 

carbonated  water  is  often  gratefully  received,  or  water  acidulated  with 
lemon  or  orange  juice. 

There  is  no  o})jection  to  the  use  of  ice-creain,  [>rovidcd  it  is  taken  in 
moderation. 

Medical  Treatment  in  the  Complicated  Cases.-— Mild  cases  of 
measles  require  but  little  medication ;  the  nursing  is  of  greater  importance. 
It  may  be  necessary  to  relieve  constipation  in  the  beginning.  No  irritant 
purgatives  should  be  employed,  but  rather  such  gentle  remedies  as 
castor  oil,  elixir  of  cascara,  or  syrup  of  rhubarb,  or  a  simple  enema 
may  be  given.  Drastic  drugs  might  lead  to  a  catarrhal  inflammation 
of  the  intestines,  to  which  measles  patients  are  already  predisposed. 
More  often  the  physician  will  be  called  upon  to  check  excessive 
bowel  movements.  If  these  are  allowed  to  continue  they  soon  ex- 
haust tlie  vitality  of  the  patient.  Usually  the  diarrhoea  can  be  con- 
trolled by  a  mixture  containing  paregoric  and  bismuth;  if  this  does 
not  suffice  the  deodorized  tincture  of  opium  may  be  used  instead  of 
paregoric. 

Where  the  bronchial  catarrh  is  slight  no  treatment  is  necessary. 
When  there  is  much  cough  it  will  be  necessary  to  allay  it  by  one  of  the 
simple  cough  mixtures.  The  well-known  "brown  mixture"  may  be  admin- 
istered or  a  combination  containing  a  little  bromide  of  soda  and  ipecac- 
uanha may  be  used.  For  severe  and  incessant  cough  one  may  be 
obliged  to  resort  to  opium;  it  must  be  remembered  that  this  drug  must 
be  used  with  caution  in  young  children.  Five  to  twenty  drops  of 
paregoric,  according  to  the  age  of  the  child,  may  be  given  every  few 
hours. 

The  fever,  when  of  moderate  grade  (102°  F.),  will  require  no  treatment. 
It  is  customary  to  prescribe  some  simple  febrifuge  containing  a  little 
tincture  of  aconite,  potassium  citrate,  and  spirits  of  nitrous  ether;  this 
preparation  has  a  gentle  diuretic  and  diaphoretic  action.  When  the 
temperature  reaches  104°  or  105°  F.,  and  particularly  when  it  is  accom- 
panied by  marked  nervous  symptoms,  such  as  restlessness,  delirium, 
stupor,  or  convulsions,  more  active  antipyretic  treatment  is  demanded. 
Of  all  measures  for  the  reduction  of  temperature,  hydrotherapy  is  to 
be  preferred.  Cold  tub  baths  are  usually  not  well  borne  by  young 
children,  and  it  is  best  to  employ  tepid  or  warm  baths,  except  where 
the  fever  cannot  be  thus  controlled.  Immersion  in  a  bath  of  85°  F.  to 
90°  F.  will  frequently  bring  down  the  temperature  and  quiet  the  disturbed 
nervous  system.  These  baths  may  be  repeated  as  often  as  the  occasion 
demands.  In  those  cases  in  which  the  temperature  is  not  sufficiently 
controlled  by  this  means,  recourse  may  be  had  to  the  use  of  cold  sponge 
baths  or  the  use  of  the  wet  pack.  The  ice  cap  may  be  used  as  an  adjunct 
to  any  of  these  measures. 

When  the  temperature  is  high  and  the  extremities  cold,  the  patient 
may  be  immersed  in  a  hot  bath  with  or  without  the  addition  of  mustard; 
in  such  cases  the  ice-bag  should  be  applied  to  the  head.  The  cold  bath 
under  such  circumstances  is  badly  borne,  as  the  depression  is  too  great 
for  an  already  weak  heart. 


542  MEASLES 

The  hot  bath  with  mustard  is  also  useful  in  those  cases  in  which  the 
eruption  is  imperfectly  developed  or  unusually  slow  in  making  its 
appearance. 

The  reduction  in  the  body  temperature  is  accompanied  by  an  amelio- 
ration of  the  pronounced  nervous  symptoms  which  accompany  hyper- 
pyrexia. Where  for  any  reason  hydrotherapy  cannot  be  employed,  one 
may  resort  to  the  use  of  some  of  the  coal-tar  antipyretics.  Antipyrin 
usually  acts  very  well  in  children.  It  has  been  extensively  employed 
by  many  physicians  with  satisfactory  results.  Not  only  is  there  a 
reduction  in  the  temperature,  but  violent  nervous  manifestations,  when 
present,  are  promptly  quieted.  One  to  3  grains  repeated  according 
to  indications  will  usually  suffice.  Comby  has  used  this  drug  extensively 
in  measles,  giving  it  in  dosage  of  7|  to  15  grains.  We  would  feel  a 
hesitancy  about  administering  such  a  dose  to  a  child,  yet  Comby  states 
that  he  has  never  seen  any  bad  results  therefrom;  a  reduction  of  temper- 
ature of  one  or  two  degrees  was  obtained,  which  lasted  from  two  to 
four  hours.  Phenacetin  may,  if  desired,  be  employed  instead  of  anti- 
pyrin. While  these  drugs  usually  act  well,  hydrotherapy  is  ordinarily 
to  be  preferred. 

Treatment  of  Complications. — Measles  as  an  uncomplicated  disease 
nearly  always  ends  in  recovery;  it  is  its  complications  which  render  it 
frequently  a  grave  and  fatal  affection.  The  preventive  measures  to  be 
pursued  have  already  been  discussed.  The  complicating  disorders  must 
be  treated  much  in  the  same  manner  as  when  they  occur  independently 
of  measles. 

Nervous  Symptoms. — The  ushering  in  of  an  attack  of  measles  with 
convulsions  is  not  of  bad  augury  unless  they  persist;  convulsions  in 
children  take  the  place  of  the  chill  in  adults.  Where  the  seizure  is  brief 
no  special  treatment  is  necessary;  when  it  is  prolonged  or  repeated 
there  is  a  possibility  of  a  cerebral  hemorrhage  resulting  therefrom  and 
measures  thould  be  taken  to  check  the  convulsions.  A  few  inhalations 
of  chloroform  will  frequently  control  the  paroxysm,  after  which  chloral 
hydrate  or  antypyrin  should  be  administered.  An  ice-bag  to  the  head 
will  also  be  found  to  be  of  assistance. 

Restlessness,  stupor,  or  delirium  can  be  controlled  by  the  hydro- 
therapeutic  measures  mentioned,  for  they  almost  always  occur  in 
association  with  high  temperature. 

Skin. — The  skin  should  be  kept  scrupulously  clean  throughout  the 
attack;  this  may  be  accomplished  by  sponge  baths  with  alcohol  and 
water  or  mild  antiseptic  solutions. 

Itching  of  the  skin  may  be  so  intense  as  to  necessitate  measures  for 
relief.  A  lotion  containing  1  drachm  each  of  carbolic  acid  and  glycerin 
to  the  pint  of  water  or  an  ointment  of  10  grains  each  of  carbolic  acid 
and  camphor  to  the  ounce  of  vaselin  will  control  the  pruritus.  Not 
infrequently  impetigo  vesicles  and  pustules  develop  about  the  nose, 
mouth,  or  ears  as  a  result  of  pyogenic  infect'.on  of  the  skin  from  purulent 
discharges.  An  ammoniated  mercury  ointment,  10  grains  to  the  ounce, 
will  effect  the  disappearance  of  these  lesions. 


Tm<:  treatmi':nt  of  mj'JA,s/j<js  543 

Ulcerative  Stomatitis. — Ulcerative  stomatitis  is  to  be  treated  by  tJie  fre- 
quent use  of  antiseptic  rnoufli  washes,  such  asdihilcd  Dobell's  sohjfion 
or  hydrogen  peroxide.  Where  tiiere  is  much  ulcerative  action  benefit  will 
be  derived  from  painting  the  ulcers  each  day  with  tincture  of  iodine. 

Gancrum  Oris. — When  that  frightful  complication  cancrum  oris 
develops  prompt  and  energetic  treatment  is  demanded.  As  soon  as  the 
condition  is  discovered  the  patient  should  })e  given  a  few  whiffs  of  an 
anaesthetic,  the  pultaceous  mass  upon  the  mucous  surface  of  the  cheek 
curetted  away,  and  the  base  thoroughly  cauterized  with  fuming  nitric  acid. 
If  despite  this  the  gangrene  should  appear  upon  the  cutaneous  surface  of 
the  cheek,  the  affected  area  should  be  promptly  and  freely  excised.  One 
must  not  be  deterred  for  fear  of  the  resulting  disfigurement,  for  only 
the  most  radical  treatment  will  give  a  chance  for  life.  The  vital  powers 
should  be  supported  by  concentrated  liquid  nourishment  and  by  stim- 
ulants. 

Goryza. — When  coryza  is  an  annoying  symptom  considerable  relief 
will  be  afforded  by  irrigating  with  saline  solution  and  subsequently 
spraying  the  nares  with  albolene  containing  2  grains  of  menthol  to  the 
ounce     This  procedure  may  be  repeated  every,  few  hours  if  necessary. 

Nose-bleed.^ — Nose-bleed,  when  moderate,  need  not  be  interfered  with, 
as  it  lessens  the  congestion  of  the  nasal  structures.  W^hen  it  is  severe 
or  persistent  it  may  be  checked  by  the  injection  of  hot  water,  a  solution 
of  antipyrin,  or,  if  necessary,  the  perchloride  of  iron.  When  the 
hemorrhage  is  from  the  anterior  portion  of  the  nose  the  nares  may  be 
plugged  with  sublimated  absorbent  cotton. 

Gonjunctivitis. — The  conjunctivitis  is  often  sufficiently  pronounced  to 
require  measures  for  its  relief.  The  light  in  the  sick-room  should  be 
kept  subdued.  Cool,  moist  compresses  may  be  applied  to  the  lids  and 
a  boric  acid  eye  wash  instilled  several  times  a  day.  Where  there  is 
considerable  gluing  together  of  the  lids  by  the  drying  of  the  conjunctival 
discharge,  the  borders  of  the  lids  should  be  anointed  with  an  ointment 
of  \  grain  of  the  yellow  oxide  of  mercury  to  the  drachm  of  vaselin. 

Laryngitis. — Laryngitis  is  present  in  the  vast  majority  of  cases.  When 
it  is  mild  the  application  of  moist  compresses  to  the  neck  will  be  all 
that  is  necessary.  These  may  be  applied  cold  and  changed  three  or 
four  times  in  the  course  of  twenty-four  hours.  When  the  laryngitis  is 
accompanied  by  spasmodic  paroxysms  the  compresses  should  be  hot. 
The  atmosphere  of  the  room  should  be  kept  moist.  When  symptoms  of 
croup  are  pronounced  it  is  a  good  plan  to  make  a  tent  of  the  bed- clothing 
and  direct  the  spout  of  a  croup  kettle  into  the  tent.  Lime-water  may 
be  evaporated  instead  of  ordinary  water;  the  patient  should  also  be 
encouraged  to  drink  freely  of  water,  particularly  alkaline  waters. 
Jacobi  recommends  the  internal  administration  of  the  iodide  of  potas- 
sium in  moderate  doses  and  also  an  opiate  at  night.  Dover's  powder 
has  long  been  regarded  as  a  useful  remedy  in  relieving  laryngeal  spasm. 

In  laryngeal  stenosis,  von  Jiirgensen  advises  a  h;^^odermic  injection 
of  apomorphine  hydrochlorate  sufficient  to  induce  vomiting.  It  should 
be  remembered  that  a  persistent  stenosis  of  the  larynx  after  measles 


544  MEASLES 

means  the  presence  of  a  false  membrane,  and  that  this  may  result 
either  from  the  presence  of  the  streptococcus  or  the  diphtheria  bacillus. 
This  serious  condition  requires  prompt  and  energetic  treatment.  If 
diphtheria  is  suspected  the  usual  treatment,  including  the  administration 
of  antitoxin,  should  be  immediately  instituted.  The  prognosis  appears 
to  be  equally  grave  whatever  be  the  character  of  the  membranous  exu- 
date, for  bronchopneumonia  is  extremely  apt  to  supervene.  When  the 
stenosis  leads  to  urgent  dyspnoea,  intubation  becomes  necessary.  This 
operation  will  give  temporary  relief,  but  it  seldom  averts  the  fatal 
outcome. 

Bronchopneumonia. — Bronchopneumonia  is  the  most  frequent  and  the 
most  fatal  of  all  of  the  complications  of  measles.  Every  effort  should  be 
made  to  prevent  the  development  of  this  dreaded  complication  by 
attention  to  hygiene  and  nursing,  as  already  pointed  out.  The  utmost 
vigilance  is  necessary  to  detect  the  earliest  symptoms  of  this  disease. 
Holt  aptly  says:  "Very  little  can  be  done  for  the  disease,  but  much  can 
be  done  for  the  patient."  The  chest  should  be  enveloped  in  a  jacket 
of  cotton-batting  or  oiled  silk.  Counterirritation  in  the  form  of  mustard- 
wheat-flour  paste  may  be  applied  to  the  chest  from  time  to  time. 
When  the  temperature  is  high  and  the  pulse  of  good  volume,  ice  poultices 
over  the  chest  accomplish  a  double  purpose. 

Children  should  not  be  allowed  to  be  continuously  in  the  same  position, 
but  should  be  moved  from  time  to  time.  Infants  may  be  carried  in  the 
nurse's  arms.  Steam  inhalations  will  be  found  useful  when  there  is 
much  bronchial  secretion;  these  may  be  medicated  with  a  little  creosote. 
No  antipyretic  treatment  is  necessary  unless  the  temperature  rises  above 
103°  F.  The  coal-tar  derivatives  should,  in  general,  be  avoided,  as  they 
are  depressant  in  sufficient  dosage.  Hydrotherapy  should  be  depended 
upon  to  lower  the  temperature  when  it  is  excessive  and  to  allay  the 
accompanying  nervous  symptoms.  For  this  purpose  the  graduated  bath, 
the  wet  pack,  sponge  bath,  or  ice-cap  can  be  employed.  Friction  of  the 
extremities  during  the  bath  will  help  to  maintain  the  peripheral  circula- 
tion. Brandy  may  be  administered  before  the  bath  and  heat  applied 
to  the  feet  afterward. 

Where  there  is  much  cyanosis  a  warm  mustard  bath  with  the  ice-cap  to 
the  head  will  be  found  useful. 

The  alternate  application  of  hot  and  cold  douches  favors  deep  respi- 
ration, a  condition  eminently  to  be  desired.  Jacobi  says :  "Warm  bathing 
and  cold  affusion  in  a  warm  bath  will  be  of  good  service,  for  it  is  neces- 
sary that  the  patients,  particularly  small  children,  should  cry.  Unless 
they  cry  they  will  suffocate."  For  the  purpose  of  stimulating  deep 
breathing  and  expectoration  Thomas  recommends  the  use  of  a  folded 
sheet  wrung  out  of  cold  water  wrapped  around  the  chest;  this  procedure 
may  be  frequently  repeated,  particularly  if  the  temperature  is  high. 

Emetics  and  depressant  expectorants  are  to  be  avoided.  Carbonate 
of  ammonia  in  1  to  2  grain  dosage,  every  three  or  four  hours,  will  be 
found  of  value.  We  have  found  that  it  is  much  better  borne  when 
administered  in  milk.     Aromatic  spirits  of  ammonia  may  be  given 


THE  TREATMI'JNT  OP'  MEAHLES  645 

when  the  stomach  will  not  bear  the  carbonate.  It  is  highly  important 
to  interrupt  the  use  of  any  drug  that  disturbs  the  stomach. 

Whiskey  and  brandy  are  of  great  value,  but  should  be  reserved  until 
they  are  needed;  they  should  not  be  pushed  in  the  beginning  before 
the  heart  shows  evidence  of  weakness.  When  the  pulse  becomes  small 
and  rapid  they  are  to  be  administered  freely;  a  one-year-old  child  will 
beax  one  to  two  ounces  of  whiskey  a  day.  Strychnine  is  a  valuable 
remedy  and  maybe  given  in  doses  of  .j,',(t  of  a  grain  every  three  or  four 
hours  to  a  child  one  year  old. 

Nitroglycerin  or  the  nitrite  of  amyl  is  useful  to  tide  over  acute 
cardiac  depression. 

When  cyanosis  makes  its  appearance  oxygen  should  be  resorted  to. 
It  may  be  given  for  long  periods  freely  mixed  with  air.  A  good  plan 
is  to  introduce  the  oxygen  beneath  a  bed-tent.  Sudden  collapse  should 
be  combated  by  the  use  of  oxygen,  whiskey,  strychnine,  and  a  hot 
mustard  bath. 

In  treating  cases  of  bronchopneumonia  following  measles  in  hospitals 
it  is  a  wise  precaution  to  isolate  these  patients  from  the  uncomplicated 
measles  patients.  Holt  says:  "Twice  in  one  institution  have  I  seen 
regular  epidemics  of  bronchopneumonia  occur  with  outbreaks  of 
measles,  in  some  of  the  wards  nearly  every  case  of  measles  developing 
pneumonia." 

In  the  Hopital  des  Enfants  Malades,  at  Paris,  all  cases  of  broncho- 
pneumonia are  treated  in  isolated  compartments  in  the  ward.  The 
partitions  are  eight  feet  high  and  constructed  in  part  of  glass;  each 
compartment  is  open  at  the  top  and  has  a  window  opening  upon  the 
exterior.  It  was  deemed  desirable  to  isolate  cases  of  bronchopneumonia 
because  the  disease  was  considered  very  infectious  and  because  the 
severity  of  the  attack  appeared  to  be  diminished  thereby.^ 

Otitis  Media. — Otitis  media  is  a  common  complication  of  measles. 
If  neglected  it  may  give  rise  to  more  serious  conditions,  such  as  mastoid 
or  cerebral  abscess. 

By  the  assiduous  use  of  mild  antiseptic  solutions  in  the  nose  and 
throat  in  measles  much  may  be  done  to  prevent  extension  of  inflam- 
mation to  the  middle  ear. 

The  Eustachian  tube  of  very  young  children  is  relatively  of  large  size, 
and  pyogenic  germs  in  the  nasopharynx  can  find  ready  access  to  the 
middle  ear.  The  key-note  of  prophylaxis,  therefore,  is  cleanliness. 
The  nasopharynx  should  be  sprayed  with  warm,  bland  liquids,  such  as 
boric  acid  or  decinormal  saline  solution,  after  which  a  weak  mentholated 
liquid  vaselin  should  be  introduced.  Children  should  be  encouraged  to 
blow  the  nose  frequently  to  dislodge  the  adherent  mucus.  In  very  young 
children,  and  especially  when  adenoid  vegetations  are  present,  Downie^ 
advises  gentle  inflation  of  the  nostrils  by  means  of  the  PoUitzer  bag. 
This  manipulation  should  not  be  entrusted  to  a  nurse,  but  should  be 
performed  by  the  physician  himself.    The  child  is  instructed  to  forcibly 

'  Quoted  by  Dawson  Williams,  loc.  cit.  2  Quoted  by  Williams. 

35 


546  MEASLES 

breathe  out  through  the  mouth  at  the  moment  the  air  is  inflated  through 
the  nose.  In  this  manner  the  mucopurulent  discharge  is  forced  into 
the  mouth  from  the  nasopharynx. 

When  otitis  develops  and  the  pain  is  severe,  measures  must  be 
employed  for  its  relief.  Heat  should  be  applied  to  the  external  ear; 
dry  heat  is  to  be  preferred  to  moist  applications.  A  hot  salt,  bran,  or 
water  bag  may  be  placed  over  the  ear,  with  a  towel  interposed.  A  few 
drops  of  a  3  per  cent,  solution  of  cocaine  instilled  into  the  ear  often 
gives  relief;  oily  solutions  for  this  purpose  are  to  be  avoided.  Tincture 
of  iodine  may  be  painted  over  the  mastoid  region.  It  will  be  necessary 
in  some  cases  to  give  an  opiate,  preferably  in  the  form  of  paregoric,  to 
relieve  the  pain  and  induce  sleep. 

The  persistence  of  the  pain  with  an  increase  in  temperature  indicates 
the  performance  of  a  paracentesis  tympani. 

Incision  should  be  made  in  the  posterior  inferior  segment.  Relief  is 
often  immediate,  although  pus  may  not  be  discharged  until  later.  It 
is  a  good  plan  to  expel  the  pus  after  puncture  by  inflation  of  the  nose 
with  the  Pollitzer  bag.  The  auditory  meatus  should  then  be  cleansed 
with  a  warm  saturated  solution  of  boric  acid  or  a  1 :  5000  solution  of 
corrosive  sublimate.  The  patient  should  be  encouraged  to  lie  upon  the 
affected  side  to  favor  evacuation.  The  use  of  absorbent  cotton  in  the 
ear  should  be  avoided. 

The  urine  should  be  examined  from  time  to  time  to  exclude  the 
presence  of  kidney  involvement.  Nephritis  is  relatively  rare  in  measles, 
but  it  has  been  discovered  often  enough  to  justify  some  care  in  this 
direction. 

During  convalescence  children  should  be  restrained  from  the  excessive 
use  of  the  eyes,  which  are  still  in  a  weak  condition.  The  persistence  of 
cough,  particularly  with  slight  evening  rises  of  temperature,  should  put 
one  on  guard  against  the  possible  development  of  tuberculosis.  Children 
thus  affected  should,  if  possible,  be  taken  to  a  locality  where  the  climate 
is  warm,  dry,  and  equable.  Creosote  and  cod-liver  oil  will  be  found  to 
be  among  the  most  useful  remedies  for  this  persistent  cough. 


CllArTEII    X. 

'  RUBELLA. 

Definition.— Rubella  is  an  acute,  contagious,  epidemic  disease,  diar- 
acterized  by  an  eruption  of  barely  elevated,  rose-colored  macules,  slight 
catarrhal  symptoms,  and  mild  febrile  disturbance,  running  a  course 
lasting  usually  three  or  four  days.  Rubella  is  a  specific  entity,  unrelated 
to  either  measles  or  scarlet  fever,  and  protecting  only  against  future 
attacks  of  the  same  affection. 

Synonyms. — German  measles;  Roiheln.  There  is  an  embarrassment 
of  riches  in  the  various  designations  applied  to  this  disease.  The 
Germans  use  the  terms  rotheln  and  rubeola;  the  French  call  it  ruheole. 
The  latter  term  being  used  at  times  to  denote  true  measles,  it  is  con- 
fusing to  apply  it  to  another  disease.  Among  other  appellations  are 
rubeola  sine  catarrho  or  incocta,  rubeola  notha,  rubeola  epidemica,  rubeola 
morbillosa,  rubeola  scarlatinosa,  rosania,  roseola,  roseola  epidemica, 
rosalia,  exantheme  fugace,  essera  Vogelii;  hybrid,  bastard,  spurious, 
or  imperfect  measles;  hybrid  or  bastard  scarlatina,  rougeole  fausse,  feuer 
masern,  German  measles,  French  measles,  etc.  The  last-named  terms 
should  not  be  employed,  for  rubella  is  a  disease  entirely  distinct  from 
measles,  although  often  strongly  resembling  it.  Griffith  counsels  the 
adoption  of  the  latin  term  rubella,  which  was  introduced  by  Veale  in 
1866  and  accepted  by  Squire  and  others. 

History. — The  vagueness  of  the  very  early  medical  writings  and  the 
use  of  confusing  names  make  it  difficult  to  establish  the  origin  of  the 
exanthematous  diseases  with  any  degree  of  accuracy.  It  is  possible 
that  the  Arabian  physician  Avicenna  (a.d.  980  to  1037)  observed 
rubella,  for  he  refers  under  the  name  of  Hhamikah  to  a  disease  related 
to  measles. 

In  the  seventeenth  century  Ingrassias,  Ballonicus,  and  Sennertus 
noted  an  eruptive  disease  similar  to  measles,  and  it  is  believed  by  some 
writers  that  this  was  rubella. 

The  first  accurate  and  undoubted  references  to  the  disease  were 
published  in  the  middle  of  the  eighteenth  century  by  the  German 
physicians  de  Bergen  (1752)  and  Orlow  (1758).  These  served  to  define 
the  nosological  position  of  rubella  (then  called  roseola)  and  to  distinguish 
it  from  both  measles  and  scarlatina.  But  some  of  the  writers  in  the 
next  half-century  evidently  confused  the  disease  with  scarlatina  and 
other  aftections,  for  neither  the  descriptions  nor  the  mortality  rate 
conform  with  that  of  rubella.  Selle  m  1780  and  Formey  in  1796 
report  virulent  and  fatal  epidemics.  Formey  states  that  between  1784 
and  1796  there  died  of  the  disease  in  Berlin  1180  persons,  while  there 


548  RUBELLA 

were  but  203  deaths  from  scarlet  fever  and  103  deaths  from  measles.^ 
While  the  specific  nature  of  the  disease  was  maintained  by  Ziegler 
(1788),  Fielitz  (1796),  Sprengel  and  Stark,  it  was  denied  by  many  later 
writers.^  Both  Goden  in  1822  and  Jahn  in  1835  were  skeptical  con- 
cerning rubella,  the  former  regarding  it  as  a  form  of  scarlatina  and 
the  latter  denying  its  existence  altogether.  Hufeland,  Frank,  and  Reil 
looked  upon  rubella  as  a  modified  scarlatina,  as  did  likewise  the  re- 
nowned Heim,  who  thought  it  was  more  to  be  dreaded  than  the  ordinary 
form  of  scarlet  fever.  The  confusion  increased.  Naumann  rejected  the 
specific  nature  of  the  disease  and  classified  his  cases  partly  as  measles 
and  partly  as  scarlatina. 

Hildebrand  in  1825  and  Schonlein  in  1832  regarded  rubella  as  the 
hermaphroditic  ofl^spring  of  scarlatina  and  measles.  They  assumed  that 
the  poisons  of  scarlet  fever  and  measles  combined  to  produce  the  disease, 
and  that,  therefore,  rubella  was  a  hybrid  between  these  two  affections. 
This  view  was  accepted  by  many  writers,  including  Geertsema  (1821), 
Busche  (1841),  Paasch  (1854),  and  Gelmo  (1858). 

The  great  Viennese  dermatologist  Hebra  repudiated  the  specificity  of 
rubella,  as  did  likewise  Canstatt  and  Gintrac.  But  the  truth  concerning 
this  third  disease  could  not  long  be  submerged.  Behrend  (1828)  and 
Wagner  (1834)  had  previously  insisted  on  the  distinctive  nature  of 
rubella,  and  the  weight  of  the  celebrated  Trousseau's  opinion  was  to 
be  added  to  theirs.  After  1860,  numerous  champions  arose  to  defend 
the  new  creed,  among  whom  were  Thierfelder,  de  Man,  Henning, 
Dnais,  Mettenheimer,  Veale,  Lindwurm,  Arnold,  Vogel,  Wunderlich, 
Dunlop,  Squire,  Gerhardt,  Emminghaus,  Kiister,  and  finally  Thomas, 
from  whom  this  list  is  quoted. 

In  England,  as  in  Germany,  belief  in  the  existence  of  this  disease 
alternated  with  periods  of  skepticism.  Willan  (1808)  observed  an 
exanthematic  disorder  allied  to  measles,  but  without  prodromal  catarrhal 
symptoms.  He  regarded  it  as  a  species  of  measles,  but  significantly 
remarked  that  "persons  receiving  the  miasm  in  this  form  are  peculiarly 
liable  to  a  second  attack  of  measles."  In  1840  Patterson  advocated 
the  specific  character  of  rubella,  and  Tripe  in  1852  and  Balfour  in 
1854  expressed  similar  opinions.  In  1866  Veale  suggested  the  name 
rubella  for  the  disease;  Murchison  (1870),  Dunlop  (1871),  and  Liveing 
(1874)  all  endorsed  its  specific  nature.  Within  more  recent  years 
epidemics  in  England^  have  been  reported  by  Cheadle  (30  cases), 
Shuttleworth,  Douglass  (50  cases),  Tongue-Smith  (145  cases),  Wilson, 
Dukes  (63  cases),  and  McLeod  in  Calcutta. 

Homans,  of  Boston,  in  1843  was  the  first  physician  in  this  country 
to  call  attention  to  the  disease.  Cotting  published  papers  on  the  subject 
in  1853  and  1871.     Howard  in  1871  and  J.  Lewis  Smith  in  1874  also 

1  Thomas  gives  the  figures  a  little  dififerently.    Deaths  from  rubella  from   1784  to  1794,  457  ;  from 
scarlet  fever,  172  ;  from  measles,  53. 

2  For  much  of  the  history  and  bibliography  of  rubella,  as  well  as  for  other  information,  we  are 
indebted  to  the  admirable  and  exhaustive  paper  of  J.  P.  Crozer  Griffith,  Medical  Record,  July  2, 1887. 

3  Mentioned  by  Griffith,  loc.  cit. 


TUi<:  i<:ti()[/)(1y  oi''  itdiU'jjjA  549 

directed  the  attention  of  American  physicians  to  the  existence  of  rubella. 
The  chief  opidoTnics  reported  in  this  country  liave  been  by  IlatfielfJ 
(110  cases),  Tark  (over  100  cases),  J^>arle  ('120  cases),  Edwards  (16G 
cases),  Kingsley  (21  cases),  Atkinson,  Griffith,  and  Hardaway. 

At  the  ])resent  day  there  is  a  unanimity  of  opinion  concerning  the 
existence  of  rubella  as  a  disease  sui  generis. 

THE  ETIOLOGY  OF  RUBELLA. 

It  is  generally  recognized  that  rubella,  like  the  other  exanthematous 
diseases,  is  derived  from  and  begets  a  like  disorder.  It  confers  pro- 
tection only  against  rubella,  and  no  immunity  against  it  is  granted  by 
an  attack  of  measles  or  scarlet  fever. 

Many  of  the  earlier  vv^riters  doubted  and  even  denied  the  contagious- 
ness of  rubella,  but  there  is  at  the  present  day  a  unanimity  of  opinion 
concerning  its  transmissibility.  As  to  the  degree  of  contagiousness  views 
are  somewhat  divergent.  Chadbourne  and  J.  Lewis  Smith  regarded 
it  as  feebly  contagious;  Thomas,  Liveing,  Tongue-Smith,  Bourneville, 
and  others,  as  less  contagious  than  measles;  Jacobi,  Dukes,  Squire,  and 
Griffith  look  upon  it  as  very  contagious,  and  Edwards^  believes  that 
"rubella  is  one  of  the  most  contagious  of  all  of  the  eruptive  fevers." 
Griffith  states  that  in  an  institution  of  100  children  37  took  the  disease 
despite  prompt  and  careful  isolation.  In  another  institution  26  per  cent, 
were  attacked.  Klaatsch  believes  that  the  degree  of  contagiousness 
varies  in  different  epidemics. 

HatfiekP  reports  an  asylum  epidemic  in  which  110  inmates  out  of  196 
contracted  the  disease. 

From  our  experience  at  the  Municipal  Hospital  we  are  inclined  to 
believe  that  a  larger  number  of  children  escape  rubella  when  this 
infection  is  introduced  into  the  wards  than  escape  measles  under  similar 
circumstances. 

Rubella  is  essentially  an  epidemic  disease  and  appears  to  be  more 
prevalent  in  the  winter  and  spring  seasons.  The  disease  is  about  as 
common  as  measles,  with  which  affection  it  has  doubtless  often  been 
confounded.  The  infection  of  rubella  seems  to  be  more  tenacious  and 
persistent  than  that  of  measles.  It  is,  therefore,  more  apt  to  be  carried 
by  fomites  in  the  garments  of  third  persons  than  is  measles.  Edwards 
alleges  that  about  75  per  cent,  of  his  cases  could  be  directly  traced  to 
infection  from  the  bunks  of  ships,  and  states  that  Emminghaus,  Thomas, 
Veale,  and  others  considered  such  an  origin  proved.  Corlett^  remarks 
that  rubella  corresponds  more  with  scarlet  fever  than  with  measles  in 
the  persistence  of  the  vitality  of  the  contagium. 

Opinions  are  at  some  variance  in  regard  to  the  period  of  greatest 
contagiousness.  Thierfelder  looked  upon  the  stage  of  convalescence  as 
the  time  at  which  the  disease  was  most  transmissible.  Squire  con- 
sidered all  stages  contagious,  from  the  pre-eruptive  period  late  into 

1  Article  on  Rubella,  Keating's  Cyclopedia  of  Diseases  of  Children,  Philadelphia,  1889,  p.  6S7. 
-  Chicago  Medical  Examiner,  August,  1881.  s  loq.  cit. 


550  RUBELLA 

convalescence.  Edwards  coincides  with  this  opinion.  Griffith  con- 
cludes, from  his  observation  in  institution  epidemics,  that  rubella  is 
certainly  contagious  at  a  very  early  date,  for  prompt  isolation  failed 
to  check  the  extension  of  the  disease. 

Age.— Rubella  behaves  much  like  measles  as  regards  age  incidence. 
Infants  under  six  months  of  age  usually  escape  the  infection,  although 
now  and  then  the  disease  will  be  contracted.  We  have  seen  a  six-month- 
old  infant  live  and  remain  well  for  months  in  a  ward  in  which  cases  of 
rubella  were  constantly  appearing.  Smith,  Roth,  Steiner,  and  Hardaway 
have  recorded  attacks  in  early  infancy,  and  Scholl  reports  a  case  occurring 
in  a  child  a  few  days  after  birth,  the  mother  having  suffered  from  the 
disease  two  months  previously.  As  in  measles,  those  who  escape  the 
disease  in  childhood  may  contract  it  in  adult  life;  indeed, even  in  advancd 
years,  as  is  attested  by  Seitz,  who  reports  a  case  in  a  woman  seventy- 
three  years  old. 

Emminghaus  saw  only  two  adult  attacks  among  42  cases.  Thomas 
noted  3  among  77  cases;  Kassowitz  observed  5  in  64  cases  and  Thomas 
but  1  in  100  cases.  Edwards  does  not  believe  that  adult  life  confers 
any  special  immunity;  he  regards  infrequent  exposures  to  the  disease, 
and  protection  by  an  attack  in  childhood  as  the  cause  of  the  compara- 
tive rarity  among  adults. 

Thomas  holds  a  rather  different  view.  He  says :  "After  the  fortieth  year 
the  susceptibility  is  nearly  lost,  and  we  may  consider  it  as  essentially 
weakened  at  puberty,  and  as  steadily  diminishing  subsequently."  In 
Forchheimer's^  experience  more  physicians  have  been  attacked  by 
rubella  than  by  all  the  other  exanthematous  diseases  taken  together. 
He  adds  that,  "with  the  exception  of  variola,  possibly  no  disease  of  this 
class  so  frequently  affects  adults." 

THE  SYMPTOMATOLOGY  OF  RUBELLA. 

Period  of  Incubation. — Different  observers  have  assigned  incubative 
periods  to  rubella  varying  from  five  days  to  three  weeks.  This  variable 
duration  is  regarded  by  Griffith  as  one  of  the  diagnostic  features  of 
the  disease  and  in  striking  contrast  with  the  fixed  incubation  period 
of  measles.  To  indicate  the  divergent  observations  of  different  clinicians 
we  present  a  table  compiled  by  Forchheimer,  to  which  we  have  made 
additions : 

1  Twentieth  Century  Practice  of  Medicine,  article  on  Rubella,  p.  180. 


77//!,'  SYMPTOMATOIJXJY  ()!<'  lilJ lihlLLA 


551 


Periods  of  Inctjra'i 

'ION   OF    RUBKLLA. 

Atkinson 

.    l-l  to  21  days. 

Hardawny    . 

2  weekKor  longer. 

Balfour. 

2  weeks. 

Hatfield 

10  days. 

Boudet  . 

.    12  to  M  days. 

.laoobi    . 

H  to  2]  days. 

Bourneville 

S  days. 

Kas.sowitz     . 

2  to  3  wcekB. 

Bricon  . 

.      8  to  10  days. 

Klaat8(;li 

2]4.  ^1  3  weeks. 

Bristowe 

1  week. 

Longstcl 

18  days. 

Cheadle 

.    15  days. 

Metteiiheirner 

2  weeks  or  longer. 

Clausen . 

.    17  to  20  days. 

Musser  . 

Just  6  days  in  lease 

CottiiiK  . 

3  weeks. 

I'icot 

2  U>  3  weeks. 

Culling  vvortl 

1       .       .      2  weeks. 

Pollock . 

f.  to  1 0  days. 

Cuomo  . 

.    17  days;  never  less. 

Juhel-r{enoy 

15  days. 

Duckworth 

.    Ifi  days. 

Robinson 

G  to  7  days. 

Duke     . 

.    15  to  16  days. 

Scholl    . 

5  to  21  days. 

Earle     . 

.    17  to  21  days. 

Steiner  . 

10  to  14  days. 

Edwards 

.    10  to  12  days. 

J.  L.  Smith   . 

7  to  21  days. 

Eichhorst 

2  to  3  vVeeks. 

Tongue-Smith     . 

14  days.    • 

Emminghau! 

2  to   3  weeks. 

Squire    . 

8  to  21  days. 

Gerhardt 

2  to   3  weeks. 

Tbierfelder  . 

2  weeks  or  longer. 

Glaister 

4  to  5  days  or  longer. 

Thomas 

2y^  to  3  weeks. 

Goodhart 

2  weeks  or  longer. 

Vacher  . 

13  days. 

Griffith 

.      5  to  11  days. 

It  is  thus  seen  that  the  incubation  may  be  either  shorter  or  longer 
than  that  of  measles.  Eleven  writers  have  noted  minimum  periods  of 
five  to  eight  days,  and  no  less  than  thirty-two  have  seen  the  period 
extend  beyond  fourteen  days. 

During  the  stage  of  incubation  the  patient  is  entirely  free  of  any 
disturbance  of  health  except,  perhaps,  in  extremely  exceptional  cases. 

Period  of  Invasion. — In  most  cases  of  rubella  this  stage  is  either  devoid 
of  symptoms  or  presents  only  mild  manifestations  which  are  readily 
overlooked.  It  would  appear  that  the  more  severe  the  attack  is  to  be, 
the  more  apt  is  it  to  be  preceded  by  pronounced  prodromal  symptoms. 
In  the  vast  majority  of  our  cases  at  the  hospital  the  eruption  was  the 
first  sign  to  attract  attention.  In  a  severe  attack  in  a  trained  nurse, 
the  symptoms  of  which  will  be  fully  detailed  later,  there  was,  however, 
a  distinct  and  protracted  stage  of  invasion.  This  nurse  was  on  night 
duty  in  a  ward  in  which  rubella  existed.  On  Wednesday,  ^March  11, 
1903,  she  was  taken  ill  with  headache  and  sudden  vomiting;  the  emesis 
was  persistent,  the  patient  vomiting  four  or  five  times  each  day  and 
retaining  nothing.  There  were  also  feverishness,  continued  headache, 
recurring  chilliness,  perspiration  during  sleep,  restlessness,  and  weak- 
ness. On  March  16th,  jour  and  a  half  days  later,  the  eruption  appeared. 
No  catarrhal  symptoms  whatever  were  present.  This  case  must  be 
regarded  as  presenting  exceptional  initial  manifestations. 

While  most  writers  refer  to  very  mild  and  brief  prodromes,  some 
rather  severe  invasive  symptoms  have  been  described.  Edwards^  noted 
in  a  severe  epidemic  in  the  Philadelphia  Hospital  the  following  s^inp- 
toms:  chilliness,  languor,  faintness,  headache  (more  or  less  severe), 
pain  in  the  back  and  limbs,  coryza,  red  and  watery  eyes,  sore  throat, 
cough,  occasionally  a  hoarse,  husky  voice,  and  a  temperature  from 


I  Loc.  cit. 


552  RUBELLA 

100°  to  103°  F.;  nausea  and  vomiting,  delirium  and  convulsions,  and 
epistaxis  were  observed  in  three  cases. 

Other  unusual  prodromal  symptoms  have  been  recorded.  Prioleau 
reports  2  cases  of  hemorrhage  from  the  eyes  and  ears;  vomiting  is 
mentioned  as  a  rare  symptom  by  Smith,  Murchison,  McLeod,  and 
Emminghaus;  convulsions  by  Smith,  Lindwurm,  Cuomo,  and  Alexander; 
delirium  by  Hardaway  and  Cuomo.  Nymann  observed  rigor  in  19  out 
of  119  cases;  Earle,  Kingsley,  Thierf elder  and  Griffith  mention  a 
slight  redness  preceding  the  eruption,  and  Cuomo  (in  7  cases)  and 
Edwards  (in  4  cases)  a  prodromal  erythema. 

Such  symptoms  as  those  detailed  are  exceptional,  but  nevertheless 
of  interest.  The  experience  of  most  observers  is  that  the  prodromal 
symptoms  are  absent  or  mild,  consisting  of  drowsiness,  anorexia, 
"liquidy"  eyes,  sneezing,  slight  cough,  etc. 

Earle  found  that  prodromal  symptoms  were  more  frequently  present 
in  adults  than  in  children. 

As  to  the  duration  of  the  invasive  period,  opinions  differ  somewhat; 
we  would  subscribe  to  the  statement  of  Thomas,  endorsed  by  Hardaway 
and  Griffith,  that  in  the  vast  majority  of  cases  the  prodromal  stage  is 
at  most  no  longer  than  half  a  day.  At  the  same  time  we  recognize 
that  it  may  vary  from  a  couple  of  hours  to  five  days.  Various  writers 
assign  periods  intermediate  between  these  two  extremes.  It  would 
seem  that  long  periods  of  invasion  presage  attacks  of  greater  severity 
than  brief  periods. 

Period  of  Eruption. — A  half -day  or  so  after  the  onset  of  mild  invasive 
symptoms,  or  in  many  cases  without  any  prodroma  at  all,  the  eruption 
of  rubella  makes  its  appearance.  The  rash  is  commonly  the  first 
symptom  to  attract  attention,  the  other  mild  initiatory  disturbances 
then  being  recalled.  Not  infrequently  a  child  awakens  in  the  morning 
with  the  eruption  visible  upon  the  face.  In  our  cases  at  the  Municipal 
Hospital,  all  of  which  developed  in  scarlet-fever  convalescents,  the 
rash  was  frequently  discovered  when  the  children  were  lined  up  for 
inspection  during  our  visits. 

Most  writers  coincide  in  the  view  that  the  eruption  appears  first  on 
the  face;  other  locations  are,  however,  mentioned  by  some  observers 
as  the  initial  site.  Liveing  and  Morris  state  that  it  appears  first  on  the 
trunk;  Murchison,  Day,  and  Balfour  speak  of  the  breast  and  arms  as 
first  attacked,  Willcocks  and  Carpenter  the  face  and  margin  of  the 
hair,  and  Thomas  and  Corlett  the  face  and  scalp.  Patterson  and 
Copland  assert  that  it  comes  out  simultaneously  on  different  parts  of 
the  body. 

In  noting  the  eruption  a  short  time  after  its  appearance  upon  the  face 
we  have  seldom  failed  to  find  it  to  some  extent  on  the  trunk  and  arms. 

In  a  severe  case  in  a  trained  nurse  (to  which  reference  has  already 
been  made)  the  eruption  was  carefully  looked  for  by  another  nurse 
occupying  the  same  room  and  was  observed  to  first  appear  at  3  a.m. 
on  the  legs  below  the  knees;  it  then  spread  upward  and  by  6  a.m.  was 
noticed  on  the  wrists.     At  3  p.m.,  the  hour  of  our  examination,  it  was 


77//';  HYMI'TOMATOr/Xjy  ()!<'  Rf/Iif'JJ.A 


553 


present  on  the  legs,  arms,  and  trunk.  'I'lie  face  was  flushet],  but  no 
distinet  eruption  was  seen  in  this  rej^ion  until  tlie  follf)\vin{(  day. 

It  is  evident  that  while  the  eruption  of  rubella  normally  appears  first 
on  the  face,  thence  extending  downward,  anomalous  cases  may  occur 
in  which  the  origin  is  in  other  regions. 

The  exanthem  spreads  (juit(!  ra})idly  over  the  body  in  the  course  of 
twenty-four  to  forty-eight  hours.  It  is  interesting  to  note,  however, 
that  the  maximum  intensity  of  the  rash  is  not  siniultaneously  noted  on 
the  entire  cutaneous  surface.    It  is  not  unusual  for  the  face,  che.st,  and 


Fin.  80 


Faint  eruption  of  rubella  upon  the  face  in  a  mild  attack. 


arms  to  show  the  eruption  at  its  height  while  the  legs  are  yet  unaffected. 
When  the  lower  extremities  exhibit  the  exanthem  in  its  greatest  mtensity 
it  is  fading  upon  the  face  and  upper  part  of  the  body.  In  other  words, 
the  rash  often  seems  to  pass  over  the  cutaneous  surface  in  a  sort  of 
wave-like  progression.  The  duration  of  the  eruption  at  its  height  in 
any  given  region  is  from  a  few  hours  to  half  a  day.  The  more  severe 
the  attack,  the  longer  is  the  period  of  maximum  intensity  and  the  longer 
the  duration  of  the  eruption. 

This  peculiar  progression  of  the  eruption  is  commented  upon  by 
Thomas  in  the  following  words:  "It  happens  with  tolerable  frequency 


554  RUBELLA 

that  the  maxima  of  its  development  occur  at  varying  times  upon  different 
portions  of  the  body."  Some  writers,  particularly  Emminghaus,  Roth, 
Mettenheimer,  and  Hardaway,  attach  to  this  eruptive  sequence  great 
importance,,  regarding  it  as  one  of  the  safest  diagnostic  signs  of  rubella. 
Griffith  agrees  with  Thomas'  statement  as  to  the  tolerable  frequency  of 
this  occurrence,  but  questions  its  diagnostic  value,  as  he  has  nearly  as 
often  observed  that  the  rash  persisted  with  equal  intensity  on  the  face 
while  it  spread  to  the  rest  of  the  body,  reaching  its  acme  everywhere 
upon  the  second  day. 

Character  of  the  Eruption. — The  eruption,  in  its  most  typical  form, 
consists  of  pinhead  to  lentil-seed  sized,  pale  rose-tinted,  slightly  elevated, 
moderately  defined  macules.  -The  lesions  are  usually  rounded  or  oval, 
but  may  be  irregular.  The  elevation  is  scarcely  sufficient  to  warrant 
the  use  of  the  term  papules,  but  is  appreciable  to  the  finger  passed 
over  the  surface  of  the  skin.  The  macules  are  ordinarily  discrete,  with 
considerable  intervening  pale  skin,  particularly  at  the  onset  of  the 
eruption  and  on  the  trunk.  Later  they  are  apt  to  become  more  closely 
set  and  may  coalesce,  with  the  production  of  irregular  patches  resembling 
measles  or  sheets  of  eruption  of  a  scarlatiniform  character. 

Ordinarily,  macular  grouping,  such  as  is  seen  in  measles,  is  absent, 
but  we  have  now  and  then  seen  distinct  linear  and  crescentic  configu- 
ration indistinguishable  from  that  observed  in  measles.  Rubella  in  its 
purest  form,  however,  shows  smaller,  more  regular,  and  more  discrete 
lesions  than  those  of  measles,  which  are  inclined  to  present  an  irregular, 
blotchy  appearance.  The  color  of  the  macules  of  rubella  has  been 
described  as  a  pale  rose-tint  or  rosy-red  by  most  writers.  Shuttleworth 
refers  to  it  as  a  brownish-red.  The  color  doubtless  varies  to  some 
extent  in  different  individuals,  as  does  the  tint  in  all  eruptive  diseases, 
but  it  may  be  said  in  general  that  it  is  ordinarily  not  as  vivid  as  the 
eruption  of  scarlet  fever,  nor  as  dusky  or  bluish  as  the  measles  exanthem. 

The  discreteness  of  the  slightly  elevated  macules  gives  the  eruption 
its  distinctive  appearance,  the  reddish  spots  standing  out  in  striking 
contrast  with  the  pale  integument.  Confluence  is,  however,  frequently 
noted  in  certain  areas,  particularly  on  the  face.  On  the  second  or 
third  day  of  the  eruption  it  is  not  uncommon  for  the  rash  to  become 
paler  in  tint  and  to  assume  a  more  diffuse  appearance. 

Pressure  or  irritation  of  the  skin  seems  to  increase  the  intensity  of 
the  eruption  and  to  encourage  confluence.  Klaatsch  and  Griffith  both 
report  cases  in  which  the  eruption  was  particularly  well  developed  in 
circular  bands  above  the  knees,  where  the  garters  had  made  pressure. 
In  scarlet  fever,  on  the  other  hand,  pressure,  such  as  is  produced  by 
garters,  is  apt  to  produce  anaemic  or  pale  bands  in  the  areas  thus  affected. 

Distribution  of  the  Eruption. — The  face  almost  invariably  exhibits 
an  abundance  of  eruption,  especially  upon  the  forehead,  cheeks,  and 
chin.  The  lesions  may  be  so  copious  as  to  produce  the  appearance 
of  slight  oedema.  The  eruption  does  not  respect  the  circumoral  region 
as  does  the  exanthem  of  scarlet  fever.  The  scalp  is  profusely  covered, 
as  is  also  the  neck.    The  chest,  abdomen,  back,  and  arms  show  rather 


Tim  HYMI'TOMATOIJXIY  OF  lUJUHLLA 


555 


less  eruption;  the  Inittocks  and  j)Ostorif)r  aspect  of  the  thighs,  owing, 
perhaps,  to  pressure,  commonly  exhi})it  eruption  in  such  j)rofusion  as 
to  present  confluent  patches.  The  legs,  as  a  rule,  are  the  seat  of  the 
least  eruption,  the  lesions  often  being  widely  scattered.  It  has  been 
asserted  by  sonic  writers  that  the  palmar  and  |)lantar  surfaces  are 
exempted,  but  this  is  not  true,  as  lesions  are  not  infrcfiuently  found 
in  these  regions  in  well-pronounced  attacks.  The  above  outline  presents 
the  distribution  of  the  eruption  in  normal  cases;  it  is  not  rare  for  depart- 
ures from  this  to  take  place. 

Barthez  and  Rilliet  have  noted  the  fading  of  the  (;ruption  followed 
by  the  reappearance  of  the  same  upon  the  same  day  or  later.  Griffith 
also  mentions  a  case  in  which  it  was  invisible  during  one  day  and 
returned. 

Duration  of  the  Rash. — The  duration  of  the  rash  is  influenced  by 
the  intensity  of  the  eruption  and  the  character  of  the  epidemic.     The 


ous  periods  a 

Aitken  . 

ssigned  by  dmerent  v 

4  to  5  days  (bad  cases 

i^riters  are  nei 

Gerhardt 

e  tabulated: 

.    J^  to  1  day. 

6  to  10). 

Griffith  . 

.      2  to  3  days 

Alexander    . 

.    14  days  (one  case). 

Hatfield 

4  days. 

Alibert  . 

.      2  to  3  days. 

Kingsley 

2  to  4  days. 

Balfour. 

4  to  6  days. 

Klaatsch 

1  to  5  days. 

Barthez . 

2  to  3  days. 

Liveing . 

5  to  7  days. 

Bourneville  . 

.      2  to  3  days. 

Maton   . 

3  to  4  days 

Bricon  . 

2  to  3  days. 

Nymann 

2  to  4  days 

Carpenter     . 

1  to  4  days. 

Picot     . 

3  to  4  days. 

Claussen 

3  days. 

Rilliet    . 

.      2  to  3  days. 

Copland 

4  to  5  days. 

J.  G.  Smith  . 

3  days. 

Corlett  . 

2  to  4  days. 

Thomas 

.      2  to  3  days. 

Edwards 

2  to  15  days  ; 

average  5. 

Trousseau     . 

1  to  2  days. 

Emminghaus 

2  to  4  days. 

Willcocks 

.      1  to  4  days 

Porchheimer 

.    not  exceedin 

J  5  days. 

It  will  be  seen  from  the  above  figures  that  the  duration  of  the  eruption 
offers  considerable  latitude.  The  long  periods  are  doubtless  isolated 
instances.  In  about  100  cases  which  we  have  recently  had  the  oppor- 
tunity of  observing,  the  rash  did  not  persist  beyond  three  days  save  in 
the  case  of  the  nurse,  in  whom  it  lasted  five  days.  In  a  great  many  of 
the  children  the  eruption  was  scarcely  apparent  after  the  first  twenty- 
four  hours;  the  average  duration  was  certainly  not  more  than  two  days. 
The  brief  duration  is,  perhaps,  to  be  accounted  for  by  the  very  mild 
type  of  the  epidemic.  The  average  duration  in  over  200  of  Edwards' 
cases  was  five  days;  the  type  of  the  epidemic  which  he  observed  was, 
however,  distinctly  more  severe  than  ours. 

The  rash  appears  to  persist  longer  in  some  regions  than  in  others, 
possibly  the  regions  of  greatest  intensity.  Edwards  says  that  the  face 
and  upper  chest  exhibit  the  most  persistent  eruption;  our  experience 
coincides  more  with  that  of  Griffith,  who  regards  the  face  and  buttocks 
as  the  seats  of  the  most  protracted  eruption. 

Anomalous  Features  of  the  Eruption. — In  rare  instances  miliary 
vesicles  have  been  noted  upon  the  reddish  macules.  This  has  been 
observed  by  Curtman,  Cuomo,  Thomas,  Hardaway,  and  Copland.^ 

1  Mentioned  by  Griffith,  loc.  cit. 


556  RUBELLA 

Petechial  spots  have  been  recorded  by  Dunlop  and  Hkewise  by 
Cheadle;  Erskine  reports  similar  lesions  on  the  uvula  and  soft  palate. 
A  purpuric  rash  was  also  observed  by  Glaister. 

Claussen  makes  mention  of  lesions  which  gave  the  impression  of 
small  shot  being  buried  in  the  skin.  Griffith  saw  an  unusual  eruption 
which  also  imparted  a  shotty  feel  to  the  finger. 

Scarlatiniform  Variety  of  Rubella. — Thus  far  reference  has  only  been 
made  to  normal  rubella  and  to  the  form  which  bears  more  or  less  of  a 
resemblance  to  measles.  There  are  other  cases  in  which  the  exanthem 
bears  a  strong  resemblance  to  that  of  scarlet  fever.  Some  writers  of 
prominence  make  no  mention  of  this  variety  and  express  astonishment 
at  any  suggestion  of  similarity  between  the  rashes  of  rubella  and 
scarlatina.  Thomas  says:  "According  to  my  observations  the  exanthem 
of  rubeola  (rubella)  possesses  a  similarity  to  that  of  measles  only,  not 
the  slightest  to  that  of  a  normal  scarlet  fever."  Bristowe  and  Bourne- 
ville  and  Bricon  entertain  similar  views.  These  opinions  may  be 
attributed  to  the  fact  that  the  scarlatiniform  variety  of  rubella  has  not 
come  within  the  range  of  the  personal  experience  of  these  physicians. 

Mention  could  be  made  of  a  large  number  of  writers  who  have 
observed  this  variety.  Hatfield  speaks  of  an  epidemic  in  which  the 
rash  in  many  cases  was  indistinguishable  from  measles,  and  in  other 
cases  strongly  resembled  scarlet  fever.  J.  L.  Smith  refers  to  a  case 
which,  had  he  been  guided  alone  by  the  eruption,  he  would  have  regarded 
as  a  mild  scarlet  fever.  Griffith  describes  a  case  in  which  the  eruption 
was  at  first  macular,  yet  on  the  second  day  it  so  closely  resembled 
scarlet  fever  that  he  was  unable  for  several  days  to  make  a  diagnosis. 
The  whole  body  was  covered  by  a  general  scarlatinal  blush  and  nowhere 
could  a  single  macule  or  papule  be  found.  A  short  time  afterward 
the  brother  took  rubella. 

We  have  seen  in  the  Municipal  Hospital  one  or  two  cases  of  rubella 
with  scarlatiniform  eruptions  in  children  convalescent  from  scarlet  fever. 

Griffith,^  from  a  careful  study  of  a  large  number  of  cases,  comes  to 
the  conclusion  that  there  are  two  easily  recognized  types  of  variation 
from  the  character  of  the  eruption  in  a  normal  case: 

1.  "An  eruption  in  which  the  spots  are  for  the  most  part  nearly  or 
fully  the  size  of  a  split  pea,  more  or  less  grouped,  and,  in  fact,  having 
the  greatest  resemblance  to  measles. 

2.  "A  rash  which  is  confluent  in  patches  or  universally  not  elevated, 
and  which  produces  a  uniform  redness  closely  simulating  that  of  scar- 
latina. Very  careful  examination  will  often  reveal  a  few  papules  amid 
the  general  diffuse  redness." 

Desquamation. — Upon  the  subsidence  of  the  eruption  a  delicate 
brownish  or  yellowish  staining  may  be  noticed  for  a  short  time. 

A  slight  branny  or  furfuraceous  desquamation  occasionally  follows 
the  disappearance  of  the  rash.  The  development  of  this  scaling  is 
proportionate  to  the  severity  of  the  attack  and  the  intensity  of  the 

1  Loc.  cit.,  p.  15. 


Tlll'l  KVMl'TOMATOfJXlY  OF  ItU I'.FLLA  F)')! 

eruption.  Many  writers,  inclufiing  Steiner,  Thomas,  Fleisclimann, 
Brodie,  McLeod,  Wilson,  Goodhart,  Cuonno,  Bourneville,  and  liricon 
have  not  ol)served  des(|naniutioii.  Eflwards,  on  tlie  other  hand,  in  a 
severe  ej)ideniic  discovered  (Jescjiiamation  in  all  of  his  cases.  In  quite 
a  number  the  scaling  was  well  marked;  in  others  it  was  limited  to 
certain  regions,  especially  the  nose.  The  buccal  cavity,  |)articularly 
the  throat  proper,  participated  in  the  desquamative  process.  The 
peeling  was  usually  furfuraceous,  beginning  in  the  centre  of  the  eruptive 
patch  and  extending  to  the  circumference.  Larger  scales  were  seen 
on  the  hands  and  feet.  The  average  duration  of  desquamation  was 
three  days,  but  Edwards  has  seen  it  last  twenty  days.  In  our  cases, 
which  it  will  be  remembered  were  very  mild,  it  was  rare  to  .see  any 
desquamation. 

Associated  Symptoms  of  the  Eruptive  Stage.  Fever. — The  extent  of 
febrile  reaction  in  rubella  is  largely  dependent  upon  the  severity  of 
the  individual  attack  and  the  character  of  the  prevailing  epidemic. 
The  variant  observations  of  different  writers  on  this  point  is  evidence 
of  the  truth  of  the  above  assertion.  There  are  some  epidemics  in  which 
there  is  but  an  insignificant  rise  of  temperature,  if,  indeed,  there  be  any 
fever  at  all.  Nymann  failed  to  observe  any  appreciable  rise  of  temper- 
ature in  58  out  of  119  cases.  Emminghaus,  Thomas,  Vogel,  Wunderlich, 
Earle,  Picot,  and  others  have  all  seen  afebrile  cases. 

On  the  other  hand,  in  severe  cases  high  fever  may  be  present. 
Edwards  saw  cases  with  temperature  of  103°  and  104°  F.  McLeod's 
cases  ranged  from  100°  to  105°  F.  Cheadle  reports  an  epidemic  in 
which  the  initial  temperature  was  103°  F.,  later  reaching  104°  and 
105°  F.  Haig-Brown  records  a  temperature  of  105°  F.,  and  Davis 
saw  a  temperautre  of  106°  F.  in  a  boy  with  a  livid  rash,  convulsions, 
and  rapidly  running  pulse. 

The  fever  is,  as  a  rule,  proportionate  to  the  extent  and  severity  of 
the  eruptive  and  catarrhal  symptoms. 

There  is  no  febrile  course  which  occurs  with  any  degree  of  constancy. 
The  evening  temperature  is,  however,  usually  1  or  2  degrees  above 
the  morning.  Most  cases  of  rubella  will  exhibit  slight  fever  varving 
between  99°  and  101°  F.  In  most  of  our  cases  the  temperature  regis- 
tered 99°  or  100°  F.    In  two  patients  it  reached  102°  F. 

It 's  not  surprising  that  some  of  the  older  writers  should  have  regarded 
rubella  as  a  hybrid  of  measles  and  scarlatina,  for  we  commonly  note 
in  this  disease  the  catarrhal  symptoms  of  the  former  and  the  angina  of 
the  latter,  but  both  in  very  mild  form. 

The  catarrhal  symptoms  commonly  affect  the  eyes,  nose,  throat,  and 
bronchial  tubes.  The  eyes  are  commonly  seen  to  be  "watery"  or 
slightly  injected.  Our  experience  coincides  with  that  of  Griffith,  who 
observed  this  symptom  in  about  one-half  of  his  cases.  It  is  uncommon 
to  find  conjunctivitis  and  photophobia  as  pronounced  as  it  is  seen  in 
measles. 

Sneezing. — Sneezing  is  a  frequent  symptom,  although  the  paroxA'sms 
may  be  but  few  and  limited  to  the  first  day  of  the  eruption.     In  none 


558  RUBELLA 

of  our  cases  did  we  note  any  distinct  discharge  from  the  nose;  neverthe- 
less, coryza  is  recorded  as  occurring  in  a  considerable  proportion  of 
cases  in  some  epidemics. 

Cough. — Cough  occurs  in  a  variable  proportion  of  cases,  depending 
upon  the  character  of  the  prevailing  epidemic.  When  it  is  present  it  is 
usually  slight  and  in  no  sense  comparable  with  the  severe  cough  of 
measles.  It  was  absent  in  the  vast  majority  of  our  cases.  Griffith  says 
a  loose,  bronchial  cough  was  frequently  present  in  his  cases  and  occa- 
sionally demanded  treatment.  In  the  severe  epidemic  observed  by 
Edwards  cough  was  generally  present,  increasing  in  frequency  and 
severity  and  occasionally  becoming  laryngeal.  In  quite  a  large  pro- 
portion of  these  cases  bronchitic  rales,  more  or  less  diffused,  were  heard. 
The  cough  lasted  about  as  long  as  the  eruption,  so  that  it  had  entirely 
disappeared  about  the  fourth  or  fifth  day. 

Sore  Throat. — Sore  throat  of  a  mild  character  is  an  extremely  common 
symptom  of  rubella.  The  angina  is  much  milder  than  that  observed 
in  scarlatina,  and  often  does  not  lead  to  complaint  on  the  part  of  the 
patient.  Without  inspection  it  would,  doubtless,  be  frequently  over- 
looked. The  congestion  is  most  pronounced  upon  the  upper  portions  of 
the  anterior  pillars.  Occasionally  a  more  serious  involvement  of  the 
throat  is  encountered,  characterized  by  enlargement  of  the  tonsils, 
swelling  of  the  pharyngeal  mucous  membrane,  and  painful  swallow- 
ing. Mild  angina  is  regarded  as  a  rather  constant  symptom  by  most 
writers. 

We  have  frequently  seen  upon  the  soft  palate  a  number  of  pinhead- 
sized,  glistening,  reddish  elevations.  Similar  reddish  spots  have  been 
observed  by  Emminghaus,  Nymann,  Gerhardt,  Picot,  Parke,  Dunlap, 
Kassowitz,  Cuomo,  and  Griffith.  Forchheimer  regards  as  a  character- 
istic exanthem  "the  small,  discrete,  dark-red,  but  not  dusky  papules" 
which  are  seen  early  on  the  soft  palate  and  which  disappear  in  twelve 
to  fourteen  hours. 

We  have  carefully  examined  the  buccal  mucous  membrane  in  a  number 
of  cases  and  have  frequently  noted  the  presence  of  discrete,  pinhead- 
sized,  deep-red  spots,  bearing  a  considerable  resemblance  to  the  macules 
upon  the  cutaneous  surface.  We  have  never  seen  the  central  bluish- 
white  dots  which  Koplik  describes  as  characteristic  of  measles. 

Hoarseness. — Hoarseness,  usually  mild  but  occasionally  severe,  has 
been  mentioned  by  Thomas,  Emminghaus,  Griffith,  Aitken,  Cheadle, 
Patterson,  Edwards,  and  others.  The  catarrhal  symptoms  sometimes 
subside  after  a  duration  of  !a  day  or  two,  but  more  commonly  disappear 
with  the  eruption.  Occasionally  a  certain  amount  of  cough  may  con- 
tinue for  some  days. 

Tongue. — ^The  tongue  is  usually  covered  with  a  thin,  grayish  coating, 
the  tip  occasionally  exhibiting  some  prominence  of  the  papillae.  While 
a  few  writers  (Balfour,  Hemming,  Tripe,  Murchison,  Burnie,  and 
Tompkins)  claim  to  have  seen  the  typical  "strawberry"  tongue  in 
rubella,  this  condition  must  be  regarded  as  exceptional.  In  some  cases 
the  tongue  is  clean  and  presents  no  deviation  from  the  normal  appear- 


TILE  SYMPTOMATOLOGY  OF  IKJIiKI.LA  550 

ance.  In  severe  cases  Edwards  states  that  tlie  tongue  may  he  dry  and 
brown. 

Lymphatic  Glands. — Enlargement  of  tlie  lympliatic  glands  lias  long 
been  regarded  as  a  symptom  of  considerable  diagnostic  im|K)rtance. 
Nearly  all  writers  are  agreed  as  to  the  constancy  of  tliis  adenopathy. 
It  must  be  remembered,  however,  that  a  general  glandular  intumescence 
occurs  in  scarlet  fever  and  to  a  lesser  extent  in  measles,  and  that  lymph- 
atic enlargement,  therefore,  does  not  specially  differentiate  rubella  from 
these  diseases. 

According  to  Griffith,  J.  F.  Meigs  regards  the  enlarged  postauricular 
gland  as  one  of  the  most  prominent  diagnostic  signs  of  rubella. 

It  is  claimed  by  some  writers  (Squire,  Thierfelder,  Glover,  Jalland, 
Strover,  Hardaway)  that  the  glands  increase  in  siz-e  often  before  the 
appearance  of  the  rash.  In  other  cases,  however,  the  glanflular  tume- 
faction may  not  be  noted  until  the  second  day  after  the  appearance  of 
the  eruption.  The  glands  behind  the  ears  and  those  lying  posterior 
to  the  sternocleidomastoid  muscles  are  those  most  frequently  enlarged, 
although  other  glands,  such  as  the  inguinal  and  axillary,  may  participate 
in  the  process.  Kassowitz  found  lymphatic  enlargement  in  but  one- 
third  of  his  cases,  and  Eustace  Smith  observed  it  only  in  certain 
epidemics. 

Nausea. — Nausea  and  vomiting  are  rare  symptoms  in  cases  of  the 
average  type.  In  severe  cases,  however,  emesis  may  be  severe  and 
persistent.  In  one  of  our  cases  the  vomiting  continued  for  several  days 
before  the  appearance  of  the  eruption,  the  patient  being  unable  to 
retain  any  nourishment  at  all.  Edwards  states  that  in  a  severe  epidemic 
in  the  Philadelphia  Hospital,  vomiting  occurred  in  a  fair  proportion 
of  the  cases  as  the  eruption  was  approaching  the  maximum.  In  five  of 
these  cases  it  was  almost  uncontrollable.  Griffith  observed  vomiting 
on  the  first  day  of  the  eruption  in  a  few  severe  cases. 

The  bowels  are  usually  normal  or  constipated.  In  a  nurse  under  our 
care,  suffering  from  a  very  mild  attack  of  rubella,  diarrhoea  was  present 
on  the  first  and  second  days  of  the  eruption. 

About  40  per  cent,  of  Edwards'  cases  had  gastrointestinal  irritation; 
this  very  unusual  complication  may  be  accounted  for  by  the  severity 
of  the  epidemic.  Among  these  cases  were  10  of  enteritis  and  2  of  entero- 
colitis. Cuomo  has  also  noted  the  presence  of  diarrhoea  in  severe  cases. 
Earle  encountered  4  cases  of  intestinal  irritation.  Balfour  found  catarrh 
of  the  colon  a  rather  common  symptom.  The  majority  of  writers  make 
no  mention  of  any  disturbance  of  the  bowels. 

Itching.— Itching  varies  both  as  to  frequency  and  intensity,  depending 
much  upon  individual  peculiarity.  It  is  present  in  only  a  minority  of 
cases  and  is  seldom  severe. 

Pulse  and  Respiration. — The  pulse  and  respiration  usually  keep  pace 
with  the  elevation  of  temperature.  The  former  may  undergo  acceler- 
ation to  140  or  150  per  minute.  Edwards  says  several  of  his  cases 
presented  well-marked  symptoms  of  heart-failure,  which  yielded,  how- 
ever, to  appropriate  treatment. 


560  RUBELLA 

The  following  case  of  rubella  in  an  adult  patient  under  our  care 
presents  many  points  of  interest: 

Miss  R.,  trained  nurse,  aged  twenty-seven  years,  had  measles  at  the 
age  of  eight  and  scarlatina  at  the  age  of  six.  Was  on  night  duty  in 
convalescent  scarlet-fever  ward  of  the  Municipal  Hospital,  in  which 
rubella  appeared  on  March  3,  1903.  Patient  had  been  exposed  to 
measles  in  another  building  five  weeks  previously. 

March  16,  1903. — On  Wednesday,  March  11th,  the  patient  was  taken 
sick  with  headache  and  sudden  vomiting.  Since  that  time  she  has 
vomited  each  day  (or  rather  night,  as  the  patient  has  continued  on 
night  duty,  not  making  known  her  illness.)  Emesis  occurred  five  or  six 
times  each  night.  Patient  claims  to  have  retained  absolutely  nothing. 
There  has  also  been  persistent  headache,  weakness,  recurring  chilliness, 
perspiration  during  sleep,  and  restlessness.  No  catarrhal  symptoms 
whatsoever;  neither  coryza,  cough,  nor  conjunctival  redness. 

Although  patient  had  felt  feverish  for  some  days,  her  temperature 
was  first  taken  on  March  15,  1903,  in  the  evening,  when  it  registered 
102°  F.  This  morning  it  is  100°  F.  Glands  about  the  jaw  and  neck 
are  not  enlarged. 

The  eruption  was  carefully  watched  for  by  another  nurse  who  occupied 
the  same  bed-room;  it  was  observed  at  3  a.m.  on  March  16,  1903, 
making  its  appearance  first  on  the  legs  below  the  knees,  then  spreading 
upward.  At  6  a.m.  the  rash  was  noticed  on  the  wrists.  At  3  p.m. 
(the  hour  of  our  examination)  the  following  notes  were  made:  An 
eruption  of  pinhead  to  lentil-seed  sized,  dusky  red,  slightly  elevated 
macules  is  seen,  quite  covering  the  legs  and  with  even  greater  profusion 
the  arms.  The  macules  form  typical  crescents  on  the  arms  and  are  also 
arranged  linearly.  In  other  places  they  run  together  and  present  an 
appearance  quite  indistinguishable  from  an  intense  measles  exanthem. 
The  upper  part  of  the  chest  shows  a  diffuse  scarlatiniform  redness. 
On  the  back  are  a  number  of  discrete  macules  which  have  just  appeared. 
The  face  shows  no  distinct  eruption,  but  the  cheeks  are  quite  flushed. 
The  buccal  mucous  membrane  exhibits  faint  reddish  spots. 

Ylth.  The  temperature  last  night  was  101f°F.  This  a.m.  it  is 
100°  F.  The  patient  is  perspiring  quite  a  little.  The  glands  at  the  angles 
of  the  jaw  are  now  enlarged  to  the  size  of  almonds  and  are  distinctly 
tender.  There  is  also  enlargement  and  tenderness  of  the  cervical 
glands.  The  eruption  has  become  fainter  and  more  confluent  on  the 
legs  and  forearms  and  has  extended  to  the  hands,  and  also  from  the 
legs  upward  to  the  thighs  and  buttocks.  In  the  latter  region  the 
exanthem  is  intense  and  of  a  morbilliform  character.  There  is  more 
eruption  on  the  back  and  chest,  in  which  region  it  has  the  form  of  dis- 
crete, lentil-seed  sized,  sharply  defined  macules.  There  is  to-day  some 
macular  eruption  upon  the  face.  The  uvula  and  soft  palate  are  slightly 
injected. 

l^th.  The  temperature  this  a.m.  is  lOOf  °  F.  The  patient  is  perspir- 
ing and  complains  of  chilliness  and  pains  in  the  back,  arms,  and  legs. 
The  eruption  is  now  faint  on  the  arms  and  legs,  but  is  still  quite  con- 


COMPLICATfONS  AND  S/<JQU/<JLA<J  OF  ItUliHIJA  5f;i 

spicuous  on  the  })ack  and  chest.  ''J'he  })atieiit  voinitf;*!  last  ni^ht  arul 
a<>;ain  this  morning. 

\Mh.  Tlie  temperature  hist  nin;ht  was  H)J;i°F.  and  this  am.  is 
100|°  F.  Patient  is  feeling  better.  The  eruption  is  still  well  marked  on 
the  chest  and  back,  where  it  shows  many  crescents.  It  is  more  })ro- 
nounced  on  the  face  to-(hay  than  at  any  ])revious  time. 

20///.  The  cruptif)n  is  still  present  on  the  back  and  chest,  but  is 
fading.     There  is  still  a  little  fever. 

2lst.  Temperature  last  night  was  99 if ° F.  This  a.m.  it  is  99,!° F. 
The  patient  is  feeling  much  better;  the  appetite  is  returning.  The 
eruption  has  practically  disappeared. 

There  were  many  anomalous  features  in  this  attack,  among  which 
may  be  mentioned  the  long  and  severe  prodromal  symptoms,  the  origin 
of  the  eruption  on  the  legs,  the  complete  absence  of  catarrhal  symptoms, 
and  the  distinctly  morbilliform  character  of  the  eruption. 

COMPLICATIONS  AND  SEQUEL -ffi  OF  RUBELLA. 

Rubella  and  chickenpox  rank  together  as  exhibiting  the  lightest 
incidence  of  complications  of  the  various  exanthematous  diseases. 
There  is  no  special  complication  liable  to  develop  during  the  course  of 
rubella,  and  in  the  vast  majority  of  cases  there  are  none. 

Bronchitis  and  'pneumonia  have  been  mentioned  by  some  writers. 
Edwards  saw  three  attacks  of  pneumonia  among  166  cases  and  Griffith 
observed  two  in  150  cases.  Ryle  and  Edwards  have  each  reported  a 
case  of  'pleurisy.  Reference  to  enteritis  and  enterocolitis  has  already 
been  made.  Severe  secondary  sore  throat  has  been  reported  by  Tongue- 
Smith,  Emminghaus,  and  Eustace  Smith. 

Hatfield  reports  2  cases  of  stomatitis  and  Edwards  4  cases.  Earle 
and  Edwards  make  mention  of  aphthce,  the  latter  noting  it  in  30  cases. 

Rheumatis7n  was  seen  once  by  Slagle  and  Edwards,  and  several  times 
by  Earle.    Endocarditis  has  likewise  been  observed. 

Several  cutaneous  complications  have  been  recorded.  Alexander 
records  5  cases  of  facial  erysipelas;  urticaria  is  mentioned  by  Slagle, 
Earle,  and  Cullingworth;  febrile  a^dema  and  cedema  of  the  legs  have  been 
described.  Miliaria,  furunculosis,  and  pemphigus  have  been  recorded 
as  rare  complications. 

Blepharitis,  conjunctivitis,  phlyctenular  keratitis,  and  otorrhaa  have 
been  met  with.  Mettenheimer  speaks  of  chronic  nasopharyngeal 
catarrh,  permanent  swelling  of  the  tonsils,  and  gingivitis.  Painful 
enlargement  of  the  thyroid  gland  was  observed  by  Slagle  in  6  cases. 

Albuminuria. — Hatfield  found  albumin  in  the  urine  twice  and 
Cuomo  three  times.  Kingsley,  Cheadle,  Duckworth,  and  Reed  each 
record  a  case.  We  noted  transient  albuminuria  in  a  case  of  rubella 
sent  into  the  scarlet-fever  wards  as  a  case  of  scarlatina;  the  patient 
clearly  had  rubella  and  was  discharged  in  ten  days.  In  an  attack  of 
rubella  in  a  girl  suffering  from  postscarlatinal  nephritis,  swelling  of 
the  eyelids  and  legs  followed  the  disappearance  of  the  eruption. 

36 


562  RUBELLA 

In  a  series  of  166  cases  seen  by  Edwards  albuminuria  was  present 
in  about  30  per  cent.,  but  in  the  next  100  cases  but  3  per  cent,  showed 
albumin.  In  the  first  series  9  cases  presented  well-marked  albuminous 
urine,  with  dropsy.    In  none  of  the  cases  could  tube  casts  be  found. 

Most  of  the  complications  above  described  excite  interest  rather 
because  of  their  rarity. 

Association  with  Other  Diseases. — We  have  observed  100  cases  of 
rubella  occurring  in  children  convalescent  from  scarlet  fever.  In  none 
of  these  cases  did  it  occur  earlier  than  the  fourteenth  day  of  the  dis- 
ease and  usually  considerably  later.  (About  one-half  of  these  children 
had  previously  in  their  life  had  measles.)  We  have  also  seen  rubella 
in  children  convalescing  from  a  mixed  attack  of  scarlatina  and  diph- 
theria. 

In  one  little  girl  still  scaling  from  scarlet  fever,  and  showing  the  crusts 
of  a  profuse  chickenpox  eruption,  a  well-marked  eruption  of  rubella 
appeared. 

Relapse. — We  have  never  observed  a  relapse  in  rubella,  and  from 
the  absence  of  reference  to  such  instances  on  the  part  of  most  writers 
it  is  evident  that  such  occurrences  are  uncommon.  Nevertheless, 
competent  observers  have  recorded  instances  of  recurring  outbreaks. 
Emminghaus  reports  relapses  in  3  cases  and  Earle  in  2  cases.  Edwards 
noted  it  once  on  the  fourth  day  and  once  on  the  twentieth.  Griffith 
noted  a  recurrence  once  at  the  end  of  eleven  days  and  twice  after  a 
period  of  three  weeks.  Kostlin,  Lindwurm,  Golson,  and  Kingsley  have 
also  testified  to  the  occurrence  of  relapses.  The  recurrent  attack  may 
equal  the  original  in  the  intensity  of  its  symptoms  or  it  may  be  milder. 

There  does  not  appear  to  be  a  single  authentic  case  recorded  of  actual 
second  attack — i.  e.,  due  to  a  second  infection  and  occurring  after  a 
period  of  months  or  years.  It  may,  therefore,  be  said  that  one  attack 
of  rubella  offers  protection  against  subsequent  infection. 

THE   DIAGNOSIS  OF  RUBELLA. 

The  diagnosis  of  an  atypical  case  of  rubella,  particularly  when  occur- 
ring sporadically,  may  be  attended  with  the  greatest  difficulty.  In  its 
classic  form  and  especially  during  epidemic  prevalence  the  diagnosis  is 
a  very  simple  problem.  There  is  no  one  symptom  which  in  itself  is 
characteristic;  the  diagnosis  must  be  made  from  a  consideration  of  the 
composite  symptomatology. 

Measles. — ^Measles  is  the  disease  which  bears  the  closest  resemblance 
to  rubella,  and  which  has,  doubtless,  been  most  often  confounded  with 
it.  The  differential  diagnosis  between  these  two  diseases  may  be 
prefaced  by  the  remark  that  a  morbilliform  exanthematous  affection 
occurring  as  an  epidemic  among  children  who  have  had  measles  is  in 
all  likelihood  rubella. 

A  confusion  between  measles  and  rubella  may  arise  when  the  former 
disease  presents  itself  in  very  mild  form  or  when  rubella  appears,  as  it 
sometimes  does,  with  severe  manifestations.     The  history  as  to  the 


77//';  l>fy\aNOS/S  OF  IWIihlLLA  563 

previous  occurrence  in  the  patient,  of  measles  or  rubella  is  evidenee  of 
an  important  elinracter.  It  is  nncommon  for  measles  to  attack  an 
individual  twice  and  still  rarer  for  rnlx-lla  to  act  in  this  manner. 

The  incubation  period  of  rub(^lla  is  from  five  days  to  three  weeks. 
Griffith  regards  the  variable  duration  of  this  stage  as  comy)arefl  with 
the  fixed  incubation  ])eriod  (abotit  ten  or  eleven  days)  of  measles  as  a 
feature  of  diagnostic  im})ortance. 

The  prodromal  stage  is  very  brief,  rarely  lasting  more  than  twenty- 
four  hours,  or  it  may  be  absent  altogether.  Slight  conjunctival  redness, 
sneezing,  and  sore  throat  maybe  present.  In  measles  there  is  a  distinct 
pre-emptive  stage  characterized  by  considerable  fever  and  marked 
catarrhal  symptoms  affecting  the  eyes,  nose,  larynx,  and  bronchial  tubes. 
The  catarrhal  symptoms  are  more  pronounced  in  mild  attacks  of  measles 
than  in  severe  attacks  of  rubella.  Some  redness  of  the  throat  is  usually 
present  in  rubella,  whereas  in  measles  sore  throat  may  be  a}>sent. 

Pinkish  pjnhead-sized  elevations  are  at  times  observed  upon  the 
soft  palate  in  rubella.  The  buccal  mucous  membrane  sometimes  exhibits 
reddish  spots.  The  bluish-red  spots  surmounted  by  whitish  dots 
described  by  Koplik  as  characteristic  of  measles  are  not  seen  in  rubella. 

Fever  m  rubella  usually  ranges  from  99°  to  101°  F.,  rarely  exceeding 
this.  In  measles  fever  is  a  prominent  symptom,  commonly  registering 
103°  F.  or  more.    It  is  much  more  protracted  in  measles  than  in  rubella. 

The  eruption  in  rubella  spreads  more  rapidly,  fades  on  one  part 
while  spreading  to  another,  and  is  of  brief  duration  (one  to  three  days). 
It  consists  of  discrete,  pale  rose-red,  slightly  elevated,  pinhead  to  pea- 
sized  macules.  In  measles  the  eruption  spreads  more  slowly,  reaches 
a  maximum  intensity  simultaneously  all  over  the  body,  and  lasts  for 
four  or  five  days  or  longer,  being  followed  by  a  staining  of  the  skin. 
The  color  is  a  deep  red,  at  times  being  bluish.  The  macules  are  larger 
than  in  rubella,  irregularly  grouped,  often  being  disposed  in  crescents, 
and  presenting  a  distinctly  blotchy  appearance. 

Glandular  enlargement  occurs  in  both  diseases,  but  is  more  prominent 
in  rubella,  intumescence  and  tenderness  of  the  postauricular  and  post- 
cervical  glands  being  frequently  present. 

Measles  is  not  infrequently  complicated  by  pneumonia,  an  occurrence 
which  is  extremely  rare  in  rubella. 

Children  with  rubella  are  often  so  little  disturbed  as  to  complain 
about  being  put  to  bed.  Measles  is  accompanied  by  an  amount  of 
prostration  and  weakness  which  cause  the  patients  to  seek  their  beds. 

The  above  differentiation  w^ll  suffice  for  ordinary  cases.  We  occa- 
sionally encounter,  however,  attacks  of  measles  which  present  anomalous 
features.  The  fever  may  be  extremely  slight,  the  eruption  may  be  poorly 
marked,  or  the  catarrhal  symptoms  may  be  almost  in  abeyance.  On 
the  other  hand,  severe  cases  of  rubella  are  occasionally  met  with;  con- 
junctival redness,  coryza,  and  cough  may  be  developed  to  an  unusual 
degree,  and  the  fever  may  be  high.  In  other  cases  the  eruption  may  be 
deep  red,  the  macules  may  be  arranged  in  crescentic  groups,  the  rash 
persisting  for  five  or  six  days.    We  have  seen  at  least  one  case  in  which 


564  RUBELLA 

the  eruption  could  not  be  distinguished  from  that  of  measles;  in  this 
instance,  however,  catarrhal  symptoms  were  absent.  It  is  extremely 
rare  to  find  a  case  of  rubella  which  in  all  respects  answers  to  the  descrip- 
tion of  a  normal  case  of  measles,  and  it  is  still  rarer  to  find  a  series  of 
cases  which  fulfill  this  requirement. 

Scarlet  Fever. — It  is  quite  possible  to  confound  one  form  of  the 
eruption  of  rubella  with  that  of  scarlatina.  Many  writers  have  acknowl- 
edged their  inability  to  distinguish  at  times  between  the  confluent 
scarlatiniform  type  of  rubella  and  the  scarlet-fever  exanthem.  In  these 
cases  other  symptoms  than  the  skin  appearance  must  be  relied  upon 
for  the  differential  diagnosis. 

The  incubation  period  of  scarlet  fever  is  distinctly  shorter  than  that 
of  rubella,  lasting  ordinarily  from  three  to  seven  days.  The  invasive 
symptoms  are  sudden  and  quite  severe;  vomiting  occurs  in  the  majority 
of  cases,  followed  by  rapid  rise  of  temperature,  usually  to  103°  or  104°  F. 
There  is  marked  sore  throat,  the  tonsils,  soft  palate,  and  uvula  being 
particularly  affected.  The  glands  generally  are  enlarged,  but  more 
especially  at  the  angles  of  the  jaw.  The  tongue  is  at  first  coated,  later 
exhibiting  the  characteristic  red,  papillated  appearance. 

The  eruption  appears  first  on  the  neck  and  upper  chest;  the  face 
usually  shows  the  circumoral  pallor.  The  eruption  lasts  ordinarily 
five  to  six  days.  Desquamation  occurring  in  flakes  and  most  marked 
on  the  hands  and  feet  is  quite  uniform.  Middle-ear  disease  and  albumin- 
uria are  extremely  common  complications. 

It  will  be  seen  that  the  symptomatology  is  quite  different  from  that 
observed  in  rubella.  In  the  latter  disease  there  is  no  vomiting,  except 
in  rare  cases;  the  temperature  is  seldom  high;  the  eruption  begins  on 
the  face  and  is  of  short  duration;  the  "strawberry  tongue"  is  absent; 
sore  throat  is  usually  mild;  desquamation  when  present  is  branny; 
complications  are  extremely  rare.  In  addition  the  presence  or  absence 
of  an  epidemic  of  rubella  or  scarlet  fever  will  greatly  aid  in  arriving 
at  a  correct  diagnosis. 

Influenza. — Forchheimer  states  that  in  the  epidemic  of  influenza  in 
1892  many  cases  were  observed  in  which  the  differential  diagnosis 
between  scarlatina,  rubella,  and  influenza  presented  difficulties,  at  least 
in  the  beginning. 

There  may  be  present  in  influenza  an  erythematous  eruption,  M^hich 
may  be  localized  or  which  may  rapidly  spread  over  the  body.  The 
fever,  prostration,  severe  gastrointestinal  or  respiratory  symptoms  and 
the  known  prevalence  of  the  disease  will  serve  to  distinguish  it  from 
rubella. 

THE  PROGNOSIS  OF  RUBELLA. 

The  prognosis  is  absolutely  favorable  in  the  vast  majority  of  cases. 
Deaths  have  been  so  uncommon  as  to  attract  attention  by  their  rarity; 
they  have  invariably  been  due  to  complications  usually  affecting  the 
respiratory  tract. 

The  mortality  depends  somewhat  on  the  type  of  the  epidemic  and 


77/ /i'  TIIKATMENT  OF  JiUJJJ'J/J.A  505 

the  previous  coiulition  of  health  of  the  patients.  Destitute  airl  yjoorly 
noiivislied  cliilth'cn  are  rnore  apt  to  siifFcr  from  complications.  IvJwarfls 
had  a  mortiility  of  4\  per  cent.  amon<i;  a  series  of  150  cases  occurring 
in  a  destitute  class  in  a  hospital.  There  were  five  deaths  in  105  cases; 
2  died  of  pneumonia  and  enteritis,  2  of  enterocolitis,  and  1  of  tuberculous 
meningitis.    Among  his  private  cases  he  never  saw  a  death. 

Hatfield  records  a  mortality  of  9  per  cent,  occurring  among  patients 
in  bad  sanitary  environment.  Hemming,  Alexander,  Cuomo,  Slagle, 
Roberts,  McFarlan,  Davis,  and  Forchheimer  have  each  reported  deaths, 
the  last-named  writer  as  a  result  of  nephritis. 

In  about  100  cases  observed  by  us  in  children  convalescing  from 
scarlet  fever  there  were  no  deaths  and  no  complications  worthy  of 
mention;  indeed,  the  illness,  almost  without  exception,  was  of  a  most 
trivial  character  scarcely  necessitating  the  detention  of  the  children 
in  bed. 

THE  TREATMENT  OF  RUBELLA. 

What  has  been  said  in  connection  with  varicella  is  equally  true  of 
this  disease;  it  is  questionable  whether  it  is  necessary  to  isolate  rubella 
patients  in  their  homes.  The  disease  is  so  mild,  and  in  individuals  in 
average  health  so  devoid  of  complications  and  mortality,  that  such 
persons  might  be  allowed  to  take  it  when  it  appears  in  their  home. 
In  hospitals  it  is  proper  to  isolate  patients  with  rubella,  for  here  it  may 
be  inadvisable  to  superadd  to  another  disease  any  infectious  malady, 
however  mild.  The  same  may  be  said  of  institutions  in  which  there 
are  children  in  depraved  health. 

The  only  treatment  that  is  necessary  in  the  majority  of  cases  is  the 
guarding  of  the  patient  against  undue  exposure.  Where  fever  is  absent 
and  catarrhal  symptoms  slight,  one  need  not  insist  on  rest  in  bed,  although 
the  child  should  be  kept  in  a  properly  heated  and  ventilated  room. 
The  diet  should  be  regulated  according  to  individual  requirements. 
No  special  medication  is  required  unless  the  attack  be  severe  or  some 
complication  develop. 

If  it  be  desirable  to  protect  others  from  infection  the  patient  should 
be  isolated  for  about  a  fortnight. 


CHAPTEE    XI. 

TYPHUS  FEVER. 

Definition. — Typhus  fever  is  a  specific,  acute,  infectious  disease, 
characterized  by  a  continued  fever  of  about  two  weeks'  duration,  pro- 
nounced nervous  and  brain  symptoms,  and  by  the  appearance  on  the 
fourth  or  fifth  day  of  a  macular  eruption  which  tends  to  become  hemor- 
rhagic. 

Synonyms. — Spotted  fever,  petechial  fever,  ship  fever,  jail  fever,  putrid 
fever,  brain  fever,  camp  fever.  Latin,  febris  typhus;  typhus  exanthemati- 
cus;  French,  le  typhus;  German,  Exanthematischer  typhus.  Fleck  fieber; 
Italian,  il  Tifo. 

History. — It  is  impossible  to  fix  with  accuracy  the  date  of  origin  of 
typhus  fever.  The  name  "typhus"  is  mentioned  in  one  of  the  Hippoc- 
ratic  essays,  but  it  was  applied  at  this  period  to  acute  fevers  in  general, 
accompanied  by  stupor  and  disturbance  of  the  mental  faculties.  Many 
writers  are  of  the  opinion  that  Hippocrates  actually  observed  cases  of 
typhoid  fever. 

According  to  Hirsch,  the  first  clear  evidence  of  the  occurrence  of 
typhus  is  given  by  Fracastorius,  a  physician  of  Verona,  who  carefully 
chronicled  the  great  pestilence  which  began  in  Cyprus  and  swept  Italy 
on  several  occasions  between  the  years  1805  and  1830.  He  distinguished 
this  malady,  which  he  called  morbus  lenticularis,  from  the  plague.  After 
devastating  Italy,  the  epidemic  spread  to  France,  Spain,  Germany,  and 
other  European  countries.  Some  writers  claim  that  typhus  was  unmis- 
takably seen  and  described  by  Jacobus  de  Partibus  in  1463  and  by 
Agricola. 

Typhus  prevailed  in  extensive  epidemics  in  different  parts  of  Europe 
in  the  seventeenth  century.  During  all  this  time  it  was  confounded  with 
typhoid  fever.  Indeed,  these  two  diseases  were  not  generally  accepted 
as  separate  entities  until  almost  the  middle  of  the  nineteenth  century. 

Much  credit  is  due  to  that  splendid  clinician,  Hildenbrand,  of  Vienna, 
for  the  pioneer  work  in  clarifying  the  medical  comprehension  of  these 
fevers.  While  Hildenbrand  alludes  in  particular  to  the  epidemic  typhus 
of  1806,  he  states  that  he  had  been  studying  the  disease  for  upward  of 
twenty  years. 

Two  fearful  agencies  of  destruction,  war  and  pestilence,  have  ever 
travelled  in  company.  Conquest  has  often  been  purchased  at  a  frightful 
sacrifice.  Armies  have  carried  home  the  laurels  of  victory,  but  also 
death-dealing  plagues.  Almost  every  great  European  war  from  the 
time  of  Charles  the  Fifth,  in  the  middle  of  the  sixteenth  century,  to  the 
Turko-Russian  conflict  in  1878,  has  had  its  epidemic  of  typhus  fever. 


TYPllflH  FliVER  fjf;? 

The  Napoleonic  campaigns  saw  iliousaiifls  of  France's  soldiers  perish 
by  the  hand  of  this  rutliless  enemy.  Accordinj^f  to  Mic:}iaeli,'  no  less 
than  100,000  Russian  soldiers  in  tiie  Turko-Unssian  Wnr  contracted 
typhus;  of  this  number,  about  on(;-half  died.  The  mortality  was  par- 
ticularly high  among  surgeons,  60  per  cent,  of  the  stricken  sure  innbing 
to  the  disease. 

In  1799,  Rasori  described  a  disease  prevailing  in  cpidemir:  form  nbrnjf 
Genoa.  Although  the  designation  "petechial  fever"  was  given  to  this 
malady,  it  is  evident  that  it  was  typhus. 

The  widespread  military  expeditions  of  the  early  years  of  the  nine- 
teenth century  served  to  disseminate  typhus  throughout  Europe.  The 
disease  later  subsided,  only  to  reappear  from  time  to  time  in  certain 
localities.  Ireland  has  suffered  many  decimating  outbreaks,  and  has 
been  for  many  years  the  home  of  typhus  fever. 

Scotland  and  England  have  also  frequently  experienced  the  blighting 
influence  of  this  scourge.  According  to  Murchison,  one  million  persons 
were  attacked  by  typhus  in  England  in  the  epidemic  of  1847. 

Germany  has  suffered  frequent  epidemics,  the  disease  being  usually 
imported  from  the  Russian  frontiers. 

France  has  had  a  greater  exemption  from  typhus  than  most  of  the 
other  European  countries.  The  disease  nevertheless  prevailed  exten- 
sively during  the  Napoleonic  wars,  and  at  infrequent  intervals  since 
then. 

The  eastern  seaport  towns  of  the  United  States — New  York,  Phil- 
adelphia, Boston,  Baltimore,  etc. — have  seen  occasional  epidemics  of 
typhus  fever,  the  disease  being  brought  in  by  immigrants. 

According  to  Lic^aga,^  an  epidemic  of  fever  marked  by  a  spotted 
eruption  ravaged  Mexico  in  1530.  As  this  was  coincident  with  the 
epidemics  of  typhus  in  Spain  about  this  time,  the  view  is  reasonable 
that  this  disease  was  probably  typhus.  In  1545  another  severe  epidemic, 
in  all  probability  typhus,  swept  Mexico,  destroying  eight  hundred 
thousand  lives. 

Typhus  fever  is  endemic  in  the  large  cities  of  the  central  plateau  of 
Mexico;  it  increases  in  the  winter  months  and  not  infrequently  assumes 
epidemic  proportions. 

Among  the  most  important  contributions  to  our  knowledge  of  the 
disease  may  be  mentioned  the  writings  of  Sir  John  Pringle,  Hecker, 
Rasori,  Hildenbrand,  Hufeland,  Larry,  Armstrong,  Horn,  Roupell,  and, 
more  recently,  Murchison,  Virchow,  Lindwurm,  Wood,  and  Griesinger.^ 

In  the  United  States  the  writings  of  Gerhard  and  Pennock^  are 
deserving  of  special  praise.  Curschmann  says:  "To  two  American 
physicians,  Gerhard  and  Pennock,  belongs  the  credit  of  having  finally 
established  the  differentiation  (between  typhus  and  typhoid  fever).    The 

1  Quoted  by  Curschmann,  Nothnagel's  Encyclopedia  of  Practical  Medicine,  Amer.  ed.,  1901. 

2  Article  on  Typhus  Fever,  Twentieth  Century  Practice  of  Medicine,  1S98. 

3  Curschmann  gives  full  bibliographic  references  to  the  modern  Uterature  of  typhus  fever,  and 
Murchison  the  literature  before  1865. 

*  On  the  Typhus  Fever  which  Occurred  in  Philadelphia  in  1S36,  Showing  the  Distinction  between 
it  and  Dothienteritis,  The  American  Journal  of  the  Medical  Sciences,  1837,  vols.  xis.  and  xx. 


568  TYPHUS  FEVER 

clearness  of  their  differential  diagnostic  statements  is  noteworthy  for 
their  time." 

Geographical  Distribution.^ — Ireland  and  England  (more  particularly 
the  former)  have  always  been  the  home  and  distributing  centre  of 
typhus  fever.  This  pestilence  has  been  almost  continuously  present  in 
these  countries,  exhibiting  from  time  to  time  violent  epidemic  outbursts. 
The  aggregate  loss  of  life  in  Ireland  from  this  disease  has  been  appalling. 
Typhus  fever  has  fortunately  declined  in  recent  years. 

The  Russian  provinces  bordering  on  the  Baltic  Sea  and  Poland  have 
also  been  for  years  typhus-stricken  territories. 

In  Germany  the  disease  is  usually  limited  to  the  southeastern  prov- 
inces and  to  upper  Silesia,  although  in  times  of  epidemic  prevalence 
Prussia  also  suffers.  Germany  receives  its  infection  almost  exclusively 
from  the  Russian  borders. 

In  France  typhus  fever  is  seldom  widely  diffused,  although  it  is  said 
to  persist  endemically  in  certain  parts  of  Brittany. 

The  disease  is  endemic  to  a  certain  extent  in  Northern  Italy  and  also 
in  Sicily  and  the  neighboring  islands.  During  periods  of  epidemic 
extension  the  entire  country  is  overrun,  as  well  as  the  lower  provinces 
of  Switzerland. 

Austro-Hungary  has  its  endemic  centres  in  Galicia,  Silesia,  Moravia, 
and  Bohemia.  The  disease  is  practically  never  extinct  in  Turkey,  nor 
in  Persia  and  China.  India  is  comparatively  free  from  typhus  and  the 
northern  coast  of  Africa  suffers  only  at  times,  with  the  exception  of 
Algeria,  in  which  country  the  disease  has  become  endemic. 

Spain  and  Portugal  appear  to  be  protected  by  their  peninsular  isolation 
and  enjoy  a  relative  degree  of  freedom  from  typhus. 

Ireland  and  Russia  represent  the  two  important  hotbeds  of  the 
disease.  From  these  centres  the  disease  is  carried  from  time  to  time 
to  the  Central  and  Northern  European  countries,  and  to  America. 
Irish  emigration  has  frequently  brought  the  disease  to  New  York, 
Philadelphia,  Baltimore,  and  other  ports  of  the  United  States,  but  typhus 
has  never  gained  a  permanent  footing  in  this  country. 

The  disease  persists  endemically  in  the  large  cities  of  the  central 
plateau  of  Mexico.  In  these  densely  populated  districts  typhus  is  never 
absent  and  epidemic  outbreaks  occur  not  infrequently. 

THE  ETIOLOGY  OF  TYPHUS  FEVER. 

Typhus  fever  is  an  infectious  disease  due  to  a  specific  cause,  the 
nature  of  which  has  not  been  definitely  determined.  As  a  necessary 
corollary  to  this  proposition  it  must  be  accepted  that  the  disease  spreads 
from  one  individual  to  another  through  the  transmission  of  the  typhus 
germs;  this  may  take  place  directly  or  through  the  intermediation  of 
infected  articles. 

The  doctrine  of  the  spontaneous  origin  of  typhus  fever,  confidently 
asserted  not  many  years  since,  dies  with  the  acknowledgment  of  the 
germ  genesis  of  the  disease.    It  is  now  universally  recognized  that  under- 


THE  l<:TI()lJ)(iy  O/''  I'Vl'IKJH,  F/'JVh'/,'  569 

feeding  and  overcrowding  do  not  cause  typl)U.s,  l)ul  merely  favor  its 
development  and  dissemination. 

Contagiousness  of  Typhus.— Typlnis  fever  is  an  extrcjnely  contagious 
disease,  rcs('ni])ling  in  tlils  respect  the  ern})tiv(;  affections,  such  as 
measles,  scarlet  fever,  and  smallpox.  Inasmuch  as  it  is  accompanied 
quite  constantly  by  a  cutaneous  eruption  of  uniform  character,  there  is 
good  reason  to  include  typhus  among  the  exanthemata. 

While  typhus  is  an  extremely  transmissible  disease,  its  infection  is 
not  so  readily  conveyed  to  others  as  is  that  of  measles  or  smallpox. 
The  chances  of  contracting  the  disease  are  directly  proportionate  to  the 
frequency,  duration,  and  intimacy  of  the  exposure  and  to  the  degree  of 
concentration  of  infection  in  the  atmosphere. 

Ventilation  is  a  most  important  matter  in  lessening  the  dissemination 
of  the  disease.  The  poison  of  typhus  fever  commonly  requires  a  certain 
degree  of  concentration  to  acquire  an  active  infectiousness.  The 
intensity  of  the  infection  may  be  greatly  diminished  by  the  free  admixture 
of  air.  In  a  well-aired  hospital  v^ard  containing  but  a  few  patients  the 
danger  of  contracting  the  disease  is  by  no  means  as  great  as  when  the 
reverse  conditions  prevail. 

When  a  previously  unattached  individual  enters  a  hospital  ward  in 
which  a  large  number  of  typhus  patients  are  being  treated,  or  in  a 
small  and  poorly  ventilated  sick-room,  the  liability  is  great  that  he 
will  contract  the  disease. 

While  the  disease  may  be  acquired  after  a  very  brief  contact,experience 
teaches  that  the  frequency  and  duration  of  the  exposure  exert  a 
considerable  influence  upon  the  chances  of  infection.  Nurses  who  are 
continuously  and  intimately  in  attendance  upon  the  sick  run  the  greatest 
risk.  During  the  Crimean  War,  within  a  period  of  fifty-seven  days, 
603  nurses  out  of  840  in  the  service  contracted  typhus.  In  the  Turko- 
Russian  conflict  all  of  the  Sisters  of  Charity  and  80  per  cent,  of  the 
orderlies  were  attacked.^ 

The  incidence  of  typhus  in  hospitals  is  greatest  among  nurses,  next 
among  resident  physicians  and  students,  then  among  visiting  physicians, 
and,  finally,  among  ofiicials  who  make  but  occasional  visits. 

Anderson^  states  that  at  the  Fever  Hospital  at  Glasgow,  and  in  the 
English  Fever  Hospitals  generally,  the  assistants  rarely  escape  the 
disease. 

Stokes  and  Cusak^  are  authority  for  the  statement  that  from  1813  to 
1846  in  Ireland  there  were  among  physicians  568  cases  of  typhus  and 
132  deaths,  constituting  approximately  46  per  cent,  of  all  cases  and 
10.5  per  cent,  of  the  deaths.  Sixty  per  cent,  of  the  surgeons  in  the 
Russo-Turkish  War  were  stricken  by  the  disease. 

There  is  perhaps  no  disease  which  attacks  physicians  and  nurses  in 
such  large  numbers  as  typhus  fever.  Yet  when  but  few  patients  are 
treated  in  well-ventilated  wards  the  danger  is  slight.    On  several  occa- 

1  Mentioned  by  Lic^aga,  loc.  cit. 

i  Quoted  by  Lic^aga.  s  Ibid. 


570  TYPHUS  FEVER 

sions  a  few  typhus  patients  have  been  treated  in  the  Municipal  Hospital, 
and  neither  physicians  nor  nurses  have  contracted  the  disease.  Lebert 
says  that  in  1868  and  1869  typhus  was  not  propagated  in  his  hospital 
wards,  which  were  carefully  ventilated  even  in  winter. 

The  mode  of  dissemination  of  the  contagium  of  typhus  is  not  definitely 
known.  Its  poison  resembles  that  of  the  exanthematous  diseases  in  that 
it  is  apparently  contained  in  the  exhalations  from  the  patient  and 
attaches  itself  readily  to  articles  brought  into  contact  with  the  sick  or 
in  his  immediate  neighborhood. 

That  the  contagium  is  frequently  imparted  to  the  underclothing  is 
proven  by  the  frequency  with  which  washer-women,  who  have  cleansed 
the  bed  and  body  linen  of  typhus  patients,  have  contracted  the  disease. 
Indeed,  the  number  has  been  so  great  in  some  epidemics  that  women 
could  no  longer  be  secured  to  undertake  this  work. 

Curschmann  says  that  it  seems  doubtful,  or  at  any  rate  unproven, 
that  the  contagium  is  excreted  in  the  bowel  movements  and  urine. 
On  the  other  hand,  Liceaga  states  that  "infection  through  fecal  matter 
in  process  of  decomposition  is  the  only  cause  to  which  could  be  attributed 
many  small  epidemics,"  and,  further,  "individuals  have  contracted 
typhus  fever  at  a  time  when  it  did  not  prevail  epidemically,  after  having 
breathed  in  the  efiluvia  from  a  water-closet,  a  drain,  a  sewer,  or  a 
recently  opened  excavation  in  an  infected  soil."  The  importance 
attached  to  this  source  in  Mexico  is  evidenced  by  the  reports  of  the 
sanitary  inspectors  of  the  City  of  Mexico,  who  allege  that  typhus  fever 
could  be  attributed  to  emanations  from  fecal  matters  in  process  of 
decomposition  in  1108  cases  out  of  a  total  of  5749  inspections.^ 

The  infection  is  also  believed  by  some  to  reside  in  the  desquamated 
epithelium,  in  the  sputum,  and  in  other  secretions  and  excretions.  Until 
the  typhus  germ  is  discovered,  the  determination  of  the  residence  of 
the  infection  must  remain  a  matter  of  conjecture. 

The  disease  is  most  contagious  during  the  febrile  period  and  particu- 
larly at  the  acme  thereof.  The  contagiousness  appears  to  progressively 
lessen  with  the  decline  of  the  disease  and  becomes  extinguished  during 
convalescence. 

Curschmann  considers  transmission  of  the  disease  possible  during 
the  period  of  incubation  and  absolutely  certain  during  the  initial 
stage. 

After  convalescence  is  established,  the  disease  may  be  propagated 
through  infected  articles.  The  infection  may  be  carried  by  well  persons 
in  clothing,  a  fact  which  should  be  borne  in  mind  by  physicians  and 
nurses  in  attendance  upon  typhus  patients.  The  infection  may  cling 
to  objects  for  a  long  time.  A  remarkable  example  of  the  transmission 
of  the  disease  through  infected  objects  is  given  by  Pringle.^  During 
the  invasion  of  Germany  by  English  troops  in  1743,  a  number  of  tents 
which  had  been  used  for  typhus  patients  were  sent  to  Gand  for  repair. 
The  workman  and  23  assistants  working  upon  the  tents  fell  ill  with 

1  Mentioned  by  Lic6aga.  2  Quoted  by  Lic6aga,  ice.  cit. 


77//';  ICTIOLOdV  ()!<'  TV /'/If  IS  I'lCV /•:!{.  Tj?] 

typhus  fever  and  17  of  tlieiri  died.  Gand  was  at,  that,  time  free  of 
typlius  fever  and  the  workmen  \v,\A  had  no  communieation  witli  typlms 
patients. 

Doubtless  many  of  tlie  alleged  eases  of  spontaneous  origin  of  the 
disease  in  prisons  and  on  board  ships  have  been  due  to  the  presence  of 
an  unsuspected  contagium  in  clothing  or  baggage. 

Typhus  fever  is  not  .spread  to  any  extent  by  (lilrial  transmission.  It  is 
the  common  experience  of  those  in  charge  of  typhus  fever  hospitals  that 
the  disease  is  not  carried  to  the  surrounding  domiciles.  Furthermore, 
the  disease  is  rarely  conveyed  from  one  household  to  another  upon  the 
opposite  side  of  the  street,  even  though  the  intervening  distance  be  very 
small.    The  striking  distance  of  typhus  appears  to  be  limited. 

Epidemics  of  typhus  are  much  more  common  in  the  cold  than  in  the 
v^^arm  months.  In  Mexico  and  other  countries  in  which  the  disease  is 
endemic,  epidemic  recrudescences  occur  during  the  winter  season. 
Curschmann  regards  the  winter  outbreaks  as  a  result  of  the  mode  of 
living  at  this  time  of  the  year. 

But  few  persons  seem  to  possess  a  natural  immunity  against  typhus. 
The  vast  majority  of  persons  will,  when  exposed  to  a  concentrated 
infection,  contract  the  disease.  Many,  however,  will  escape  when  the 
infection  given  off  is  attenuated. 

One  attack  of  typhus  protects  against  subsequent  attacks  in  the 
majority  of  cases.  There  are,  to  be  sure,  exceptions  which  occur  about 
as  frequently  as  in  the  other  exanthematous  diseases. 

Sex. — Sex  appears  to  exert  but  little  influence  upon  susceptibility  to 
the  disease. 

Age. — Typhus  attacks  persons  of  all  ages,  except  possibly  infants  at 
the  breast,  who  exhibit  about  the  same  degree  of  insusceptibility  to 
this  disease  as  to  the  other  exanthemata. 

The  disease  is  most  common  in  youth  and  in  early  and  middle  adult 
life,  from  the  ages  of  ten  to  forty  years.  The  very  aged  are  not  spared, 
for  persons  over  the  age  of  eighty  are  every  now  and  then  attacked. 

There  are  certain  factors,  such  as  underfeeding  and  overcrowding, 
which  must  be  regarded  as  strong  predisposing  and  contributory  causes 
of  typhus  fever.  Typhus  is  most  prevalent  in  those  localities  where 
poverty  and  all  that  it  entails  is  most  pronounced.  In  Ireland  epidemics 
have  repeatedly  followed  failure  of  crops  and  its  resulting  famine  and 
distress. 

Dr.  Osborne,  describing  the  privations  of  the  Irish  people  and  their 
relation  to  typhus,  in  1816  and  1817,  says:  "Families  consisting  of  many 
individuals  were  found  in  garrets  and  cellars,  with  no  covering  but  the 
remnants  of  clothing  too  contemptible  for  even  the  pawnbroker's  avarice, 
water  their  only  drink,  and  food,  if  any,  the  offal  collected  from  the 
slaughter  houses." 

Brittany  appears  to  be  the  only  province  in  France  in  which  tA-phus 
has  shown  a  tendency  to  become  endemic,  and  the  poverty  of  this 
province  is  similar  to  that  of  Ireland.  In  Silesia  much  the  same  con- 
ditions prevail. 


572  TYPHUS  FEVER 

Overcrowding. — Overcrowding  plays  an  important  part  in  the  spread 
of  typhus  fever,  doubtless  by  effecting  a  concentration  of  the  poison  and 
favoring  its  transmission  to  many  individuals.  Therefore,  the  disease 
commonly  breaks  out  in  prisons,  barracks,  lodging-houses,  ships,  and 
badly  constructed  hospitals.  The  two  English  cities  which  are  most 
densely  populated,  and  in  which  people  are  most  crowded  in  restricted 
quarters,  are  Liverpool  and  London,  and  these  cities  are  those  which 
habitually  have  most  typhus. 

Susceptibility  to  typhus  fever  is  greatly  increased  by  debilitating 
influences,  which  lower  the  resisting  power  of  the  individual.  Phys'cal 
exhaustion,  mental  anxiety,  intemperance,  underfeeding,  exposure,  and 
all  the  accompaniments  of  poverty  and  misery  are  included  in  this 
category.  In  addition  various  acute  and  chronic  diseases  may  act  as 
strong  predisposing  causes. 

Typhus  fever  more  than  any  other  disease  follows  in  the  path  of 
war  and  famine;  it  is  essentially  a  disease  of  the  poverty-stricken  and 
miserable. 

THE  BACTERIOLOGY  OF  TYPHUS  FEVER. 

No  one  at  the  present  day  would  hazard  a  belief  in  the  spontaneous 
origin  of  typhus  fever.  The  epidemicity  and  general  behavior  of  the 
disease  indicate  that  typhus  fever  is  transmitted  by  a  micro-organism 
in  the  same  manner  as  the  other  acute  exanthematic  diseases. 

As  is  true  of  nearly  all  of  the  exanthemata  at  the  present  time,  the 
microbic  cause  of  typhus  has  not  yet  been  isolated  and  positively  identi- 
fied. The  recorded  researches  into  the  bacteriology  of  the  subject  will 
be  briefly  referred  to. 

Moreau  and  Cochez^  in  1888  isolated  a  bacillus  from  the  blood  and 
urine  of  typhus  patients  which  bore  a  resemblance  to  the  typhoid 
organism. 

A  little  later,  Hlava,  of  Prague,  found  a  streptobacillus  in  the  blood 
of  persons  dead  of  typhus  fever.  Of  45  corpses  examined,  this  organism 
was  recovered  from  the  blood  in  two-thirds;  it  could  not,  however,  be 
isolated  from  the  viscera.  Hlava  succeeded  also  in  recovering  this 
streptobacillus  from  the  blood  in  a  certain  proportion  of  living  subjects. 
The  claims  of  Hlava,  although  conservatively  expressed,  were  later 
disputed  by  Cornil  and  Babes.^ 

Kasan  discovered  in  the  splenic  blood  of  typhus  patients  rounded 
bodies  with  filiform,  motile  prolongations,  to  which  he  gave  the  name 
"spirochetse  exanthematicse."  This  appellation  was  also  employed  by 
Lewaschew  in  describing  bodies  found  in  the  blood  of  the  spleen  and 
in  smaller  numbers  in  the  general  circulation.  The  organisms  were 
minute,  highly  refractile,  coccus-like  bodies,  some  of  which  were  shown 
to  possess  free  flagellee,  like  the  typhoid  bacillus.^ 

1  Contrib.  h.  I'^tude  du  typhus  exanth.,  Gaz.  hebdom.,  1888,  No.  28. 

2  iltude  sur  le  typhus  exanth.,  Arch.  Bohem.  de  m6d.,  1889,  tome  iii.;  also  Centralbl.  f.  Bakt.,  1890. 
5  Ueber  die  Mikro-organismen  des  Fleck  typhus,  Deut.  med.  Woch,,  1892,  No.  13,  also  No.  34. 


77//';  IWTIIOIJXIY  OF  I'VI'IKJ^H  Fl'lVICIi  573 

Thoinot  and  Calmette^  found  in  the  blood  from  the  spleen  of  5  cases 
of  typhus,  during  life,  a  micro-organism  which  was  at  times  flagellated 
and  at  other  times  amoiboid. 

Calmette  regards  the  bodies  found  by  Illava,  Lewaschew,  Thoinot, 
Babes,  Briihl  and  Dubief,  and  by  liiinself  as  different  forms  of  the 
same  organism. 

Dubief  and  BriihP  isolated  from  the  blood  of  9  typhus  patients, 
during  the  Paris  epidemic  of  1802  and  1893,  a  diplococcus  which  they 
called  the  "diplococcus  exanthematicus."  This  was  also  obtained  from 
the  air  passages  and  in  the  sputum.  The  organism  is  surrounded  by  a 
capsule  and  stains  well  with  methylene  blue.  Upon  ordinary  culture 
media  orange-yellow  colonies  are  developed.  The  authors  allege  to 
have  produced  a  typhus-like  disease  by  inoculation  of  lower  animals. 
Haushalter  and  Etienne  obtained  negative  results  in  a  search  for  this 
organism. 

Le  Gendre  recovered  from  the  blood  of  a  typhus  patient  during  life 
and  from  the  viscera  at  autopsy  a  bacillus  resembling  the  typhoid 
organism. 

Gomez,  a  Mexican  veterinarian,  working  in  the  laboratory  of  the 
Superior  Council  of  Health,  has  come  to  the  conclusion  that  the  organism 
of  bovine  typhus  is  identical  with  that  of  human  typhus.^ 

From  the  above  observations  it  is  evident  that  further  research  is 
necessary  either  to  harmonize  the  findings  already  made  or  to  bring 
new  light  to  bear  upon  the  parasitic  cause  of  typhus  fever. 

THE  PATHOLOGY  OF  TYPHUS  FEVER. 

Contrary  to  the  statements  of  some  of  the  older  writers,  there  is 
nothing  pathognomonic  or  characteristic  of  typhus  fever  in  the  autopsy 
findings.  Such  changes  are  present  as  would  indicate  the  existence  of 
an  intense  infectious  process.  Post-mortem  results  in  typhus  fever 
often  have  a  negative  value  in  excluding  the  possibility  of  the  existence 
of  typhoid  fever. 

When  death  occurs  during  the  eruptive  period,  there  will  often  be 
seen  the  petechial  spots,  which,  according  to  their  age,  will  present 
purplish,  greenish,  yellowish,  or  brownish  coloration. 

Where  considerable  ecchymotic  exudation  into  the  skin  has  occurred, 
incision  through  the  patch  will  show'  the  presence  of  blood  in  the  corium. 
Occasionally  hemorrhages  take  place  into  the  muscles,  later  giving  rise 
to  circumscribed  areas  of  necrosis  and  softening. 

The  severe  cerebral  symptoms  might  lead  one  to  expect  pronounced 
changes  in  the  nervous  structures.  Nothing,  however,  peculiar  to  the 
disease  is  observed  in  the  brain  or  its  membranes.  The  meninges  are 
usually  the  seat  of  marked  congestion  and  not  infrequently  of  hemor- 
rhages, which  may  be  extensive,  although  they  are  usually  circumscribed. 

1  Notes  sur  quelques  exam,  du  sang,  dans  le  typh.  exanth.,  Annales  de  I'lnstitut  Pasteur,  1892. 
-  Contrib.  ^  l'6tude  anat.  path,  et  bakt.  du  typhus  exanth.,  Arch,  de  mod.  expiJriment.,  1S94. 
s  Mentioned  by  LiciJaga,  loc.  cit. 


574  TYPHUS  FEVER 

Diffuse  meningitis  is  a  condition  seldom  encountered.  The  surface  of 
the  brain  is  hypersemic  and  the  cerebral  substance  upon  section  shows 
numerous  dots  of  blood.  The  cortex  of  the  brain  is  rather  softer  than 
normal  and  slightly  oedematous.  A  subarachnoid  effusion  is  nearly 
always  present,  being  clear,  turbid,  or  sanguinolent  in  character.  The 
same  is  true  of  the  ventricular  fluid,  which  is  not  infrequently  increased 
in  amount. 

The  spinal  cord  shows  congestion  of  the  pia  mater  and  effusion  into 
the  subarachnoid  space. 

The  changes  in  the  cardiovascular  apparatus  are  the  same  as  those 
observed  in  other  infectious  fevers.  The  heart  muscle  is  soft,  flabby, 
and  of  a  pale  or  yellowish-red  color,  indicating  myocardial  degeneration. 
One-sided  dilatation  of  the  heart  is  usually  present.  Endocarditis  and 
pericarditis  are  of  great  rarity. 

At  times  structural  changes  in  the  bloodvessel  walls  are  noted.  Not 
rarely  thrombi  are  found  adherent  to  the  walls  of  the  bloodvessels  of 
the  thigh.  Embolic  or  thrombotic  obstruction  of  the  arteries  of  the 
extremities  is  occasionally  noted,  giving  rise  to  gangrene  of  the  parts 
supplied  by  the  damaged  vessels. 

The  frequent  employment  of  venesection  by  the  older  physicians 
gave  repeated  opportunity  for  the  study  of  the  coagulability  of  the 
blood  in  typhus  fever.  The  blood  is  darker  than  usual  and  shows  a 
less  tendency  to  coagulate  than  under  normal  conditions.  Jiminez 
described  the  blood  as  resembling  "a  watery  fluid  holding  in  suspension 
a  very  fine  powder  of  a  dark-red  color." 

The  respiratory  organs  are  commonly  the  seat  of  pathological  changes. 
The  mucous  membrane  of  the  nose,  pharynx,  and  larynx  is  congested, 
swollen,  and  often  macerated.  Ulcerations  with  formation  of  pseudo- 
membrane  may  be  seen  in  the  pharynx  or  larynx,  and,  in  rare  cases, 
farther  down  the  respiratory  tract.  Curschmann  found  intense  laryngeal 
disease  in  4  per  cent,  of  the  cases  at  autopsy.  There  was  "marked 
reddening  and  swelling  of  the  mucous  membrane,  with  oedema  and 
erosions  or  fissures,  the  last  particularly  on  the  posterior  wall,  on  the 
epiglottis,  and  on  the  ventricular  bands." 

Unilateral  perichondritis  and  necrosis  of  the  arytenoid  cartilage  were 
associated  with  these  changes.  The  trachea,  bronchi,  and  bronchioles 
show  evidence  of  severe  catarrhal  inflammation;  the  lining  membrane 
is  reddened,  soft,  and  covered  with  an  adherent,  tenacious  mucus. 

Hypostatic  congestion  of  the  base  of  the  lungs  is  extremely  common; 
the  pulmonary  tissue  in  this  condition  is  devoid  of  air,  no  longer  crepi- 
tates or  froths,  and  is  practically  in  a  state  of  splenization. 

Lobar  pneumonia  is  common  in  some  epidemics  and  rare  in  others; 
Curschmann  says  15  per  cent,  of  his  autopsies  discovered  the  presence 
of  lobar  pneumonia,  and  Liceaga  reports  7  cases  of  extensive  pneumonia 
out  of  21  examined.  Hemorrhagic  infarcts  and  gangrene  of  the  lungs 
are  at  times  observed. 

Pleurisy  is  comparatively  uncommon;  when  it  develops  it  may  even- 
tuate in  empyema. 


77//';  HYMI'TOMATOI/XIY  Oh'  TYI'IfUS  I''KV/-JI{  Fjl Tj 

The  chief  interest  in  the  alterations  in  the  duje.Hiive  tract  attaches  to 
the  appearance  of  the  intestinal  mucous  ni(;irihrane.  Many  of  the 
descriptions  by  the  older  writers  of  the  ulcerations  found  in  the  bowel 
related  really  to  cases  of  typhoid  fever  which  were  erroneously  diagnosed. 

In  typhoid  fever  Peyer's  patches  are  hypertrophied  and  ulcerated, 
the  excavations  at  times  extending  to  such  depth  as  to  lead  to  perforation 
of  the  bowel  and  the  development  of  peritonitis.  In  typhus  fever 
Peyer's  patches  are  not  involved,  and  the  solitary  follicles  are  Iikewi.se 
usually  exempted.  The  mucous  membrane  is  congested  and  occasion- 
ally punctated   hemorrliages   into  the  mucous  membrane  are  noted. 

The  stomach  is  occasionally  congested  and  may  exhibit  small  hemor- 
rhages into  the  walls;  in  rare  cases  there  is  ecchymotic  extravasation 
and  extensive  softening. 

The  liver  is  often  enlarged  and  hypersemic  and  shows  evidence  of 
cloudy  swelling. 

The  spleen  is  enlarged  in  a  considerable  proportion  of  cases,  but  the 
swelling  is  neither  as  pronounced  nor  as  uniform  as  is  the  case  in  typhoid 
fever. 

The  kidneys  frequently  show  evidences  of  congestion  and  cloudy 
swelling.  Curschmann  states  that  in  the  Moabit  Hospital  in  Berlin,  in 
1878  and  1879,  there  were  found  5  cases  of  pronounced  recent  parenchy- 
matous nephritis  among  80  autopsies. 

THE  SYMPTOMATOLOGY  OF  TYPHUS  FEVER. 

Period  of  Incubation.^ — ^The  period  elapsing  between  the  reception  of 
the  poison  and  the  true  onset  of  the  disease  is  usually  devoid  of  symptoms. 
In  a  minority  of  cases  mild  manifestations  of  indisposition  may  be  noted, 
such  as  malaise,  loss  of  appetite,  and  vague  aches. 

It  is  somewhat  difficult  to  accurately  estimate  the  duration  of  the 
incubation  stage,  for  persons  do  not  always  take  typhus  upon  the  first 
exposure.  It  is  only  when  the  contact  has  been  single  and  brief  that 
the  length  of  the  latent  stage  may  be  satisfactorily  determined.  Of 
course,  every  possibility  of  exposure  to  another  source  of  infection  must 
be  excluded. 

The  average  length  of  the  period  of  incubation  may  be  said  to  be 
twelve  days.  In  a  not  inconsiderable  number  of  cases  it  w^ill  be  found 
to  be  four  or  five  days  less  than  this.  The  extreme  limits  of  the  period 
may  vary  from  one,  tw^o,  or  four  days  to  about  two  weeks.  INIucli  longer 
periods,  extending  to  several  months,  have  been  mentioned  by  the 
older  writers,  but  these  have  doubtless  been  based  upon  errors  of 
observation.  The  retention  of  infection  in  bed-clothing,  garments, 
baggage,  or  like  articles  might  give  rise  to  attacks  of  the  disease  which 
would  be  separated  by  long  intervals  from  previous  cases. 

General  Outline  of  the  Symptoms.— The  invasion  of  typhus  is  usually 
sudden  and  not  heralded  by  prodromal  illness.  An  abrupt  rigor  or  a 
succession  of  chilly  sensations  marks  the  onset  of  the  febrile  period. 
Chilliness  may  persist  for  several  days,  seldom  amounting,  however,  to 


576  TYPHUS  FEVER 

visible  shivering.  Nausea  and  vomiting  are  not  infrequently  present, 
but  seldom  continue  long.  Constipation  exists  in  the  vast  majority  of 
cases.  The  fever  mounts  rapidly  and  to  a  considerable  height;  ordinarily, 
the  initial  pyrexia  registers  102°  or  104°  F.  With  the  rise  in  the  temper- 
ature there  develop  the  usual  associated  symptoms  of  high  fever — 
headache,  vertigo,  insomnia,  muscular  pains,  and  prostration.  The 
headache,  which  is  severe  and  unremitting,  is  usually  located  in  the 
frontal  and  temporal  regions,  with  often  pronounced  pain  and  tenderness 
in  the  eyeballs.  Backache,  chiefly  in  the  sacral  region,  is  sometimes  a 
distressing  symptom.    Pains  in  the  legs  are  not  uncommon. 

A  frequent  early  symptom  is  nose-bleed,  which  is  observed  most 
commonly  about  the  third  day.  It  may  vary  in  severity  from  a  barely 
perceptible  bleeding  to  an  uncontrollable  and  even  fatal  hemorrhage, 
as  in  a  case  observed  by  Jiminez. 

Tinnitus  aurium  is  often  pronounced,  followed  later  by  partial  or 
complete  deafness.  The  mind  is  usually  clear  in  the  beginning,  although 
the  patient  exhibits  but  little  interest  in  his  surroundings. 

The  fades  is  so  characteristic  as  to  be  of  diagnostic  value.  The  face 
is  flushed,  dusky,  and  sometimes  slightly  oedematous;  the  eyes  are 
congested  and  heavy,  and  the  expression  dull  and  apathetic.  There 
is  evidence  of  great  muscular  relaxation,  the  patient  lying  prostrate 
upon  his  back.  Sleep  is  interrupted  by  disturbing  dreams,  which  cause 
the  sufferer  to  start. 

The  temperature  now  continues  its  ascent,  reaching  its  acme  about 
the  fourth  or  fifth  day.  With  the  increased  pyrexia  there  is  a  corre- 
sponding augmentation  of  the  pulse  rate,  which  commonly  reaches  100 
to  120;  in  children  the  pulse  is  more  rapid,  acquiring  a  frequency  of 
140  or  150  to  the  minute. 

About  the  fourth  or  fifth  day  the  most  characteristic  symptom  of  the 
disease — the  rash — makes  its  appearance.  The  true  exanthem  is,  in 
some  cases,  accompanied  or  preceded  by  a  morbilliform  rash  of  transitory 
duration,  analogous  to  the  prodromal  rashes  of  variola,  vaccinia,  etc. 
The  typhus  eruption  is  commonly  seen  first  on  the  anterior  surface  of 
the  trunk,  and  later  on  the  back,  arms,  and  legs.  The  face  and  palmar 
and  plantar  surfaces  are  usually  exempted.  The  eruption  consists  of 
pinhead  to  lentil-seed  sized,  reddish  spots  or  macules.  These  acquire 
from  day  to  day  a  deeper  coloration,  finally  becoming  purplish  and  no 
longer  disappearing  under  the  pressure  of  the  finger,  thus  evidencing 
a  hemorrhagic  extravasation  into  the  skin.  The  number  of  lesions  is 
at  first  small,  but  later  the  eruption  may  become  quite  profuse. 

The  full  development  of  the  exanthem  marks  the  height  of  the  morbid 
process.  The  symptoms  have  now  acquired  increased  severity.  The 
fever  is  at  its  maximum  and  the  pulse  is  rapid;  the  tongue  is  parched, 
dry,  and  brown ;  the  mouth  half -open,  the  teeth  covered  with  sordes,  and 
the  lips  with  blood  crusts.  A  dry  cough  denotes  the  presence  of  a 
bronchitis,  and  rales  may  be  heard  upon  auscultation.  Catarrhal 
inflammation  of  the  larynx  may  lead  to  hoarseness  or  aphonia. 

The  patient  is  profoundly  prostrated,  the  lips  scarcely  moving  on 


Tjji<:  SYMPTOM  A  romav  of  tvi'iiuh  ffvku  577 

speaking  Ay)athy  has  been  replaced  l)y  a  (loliriuin  which  in  some  cases 
is  of  a  muttering  character,  but  in  others  is  violent  or  maniacal.  Homi- 
cidal or  suicidal  efforts  may  be  attempted  and  require  the  greatest 
vigilance  upon  the  part  of  the  attendants. 

The  patient  is  unable  to  hear,  speaks  in  a  scarcely  audible  tone,  and 
is  often  too  v^eak  to  protrude  his  tongue.  Delirium,  stupor,  and  semi- 
consciousness follow  each  other  in  irregular  order.  The  abdomen  is 
tense  and  somewhat  tympanitic;  constipation  is  the  rule,  but  diarrhfjea 
may  set  in  towarrl  the  end  of  the  disease,  and  the  stools  may  be  y)assed 
involuntarily.  The  bladder  becomes  paralyzed  and  incontinence  or 
retention  results.  If  the  disease  progresses  to  an  unfavorable  termination 
the  temperature  increases  to  105°  or  106°  F.,  the  pulse  becomes  rapid  and 
feeble,  the  face  acquires  a  livid  hue,  there  is  picking  at  the  bed-clothes 
and  tremor  of  the  hands,  increasing  coma,  and  finally  death  from 
exhaustion. 

Death  may  also  result  from  the  effects  of  wild  delirium  and  physical 
exhaustion;  in  other  cases  a  bronchopneumonia  or  hypostatic  congestion 
of  the  lungs  hastens  the  fatal  outcome. 

Recovery  may  occur  in  typhus  fever  even  after  the  development  of 
alarming  symptoms.  The  disease  is  self-limited  and  not  of  protracted 
duration,  and  if  the  patient  can  be  tided  over  the  crucial  stage  rapid 
convalescence  sets  in. 

When  a  favorable  termination  is  to  occur,  a  rapid  defervescence  in 
the  temperature  is  noted  about  the  fourteenth  day;  with  the  fall  in  the 
fever,  the  patient  lapses  into  a  refreshing  slumber.  The  pulse  diminishes 
in  frequency  and  acquires  more  volume,  the  tongue  becomes  moist  and 
loses  its  coating,  the  mental  faculties  clear  up,  the  voice  returns,  and  the 
patient  expresses  a  desire  for  some  food.  The  eruption  gradually  fades 
in  color,  the  petechial  lesions  being  last  to  disappear.  Branny  desquama- 
tion usually  occurs  at  the  site  of  the  purplish  maculae  and  stains  persist 
for  a  considerable  length  of  time. 

Deafness  and  prostration  may  continue  for  a  while,  but  recovery 
from  moderate  cases  of  typhus  is  more  rapid  than  would  be  expected 
from  the  formidable  character  of  the  symptoms. 

Consideration  of  the  Symptoms  in  Detail.  Fever.— The  intensity  of 
the  fever  in  typhus  is  an  excellent  index  of  the  severity  of  the  disease. 
The  febrile  curve  has  certain  distinct  characteristics  which  distinguish 
it  from  typhoid  fever. 

The  pyrexia  rises  quite  rapidly  to  a  considerable  degree,  so  that  on 
the  evening  of  the  first  day  the  temperature  registers  102°  or  103°  F..  and 
occasionally  104°  F.  Some  of  Wunderlich's  cases  exliibited  temperatures 
from  104°  to  104.9°  F.  With  slight  morning  remissions,  the  fever  con- 
tinues its  ascent  on  the  second  and  third  days,  commonly  reaching  its 
maximum  on  the  evening  of  the  fourth.  At  this  time  the  evening 
temperature  in  cases  of  moderate  severity  will  be  in  the  neighborhood 
of  104°  F.,  whereas,  in  very  severe  attacks  it  may  reach  105°  or  107°  F. 
The  fever  now  remains  at  about  the  same  level  for  four  or  five  days, 
although  a  slight  lowering  of  the  temperature  may  be  noticed  in  the 

37 


578 


TYPHUS  FEVER 


evenings.  From  the  seventh  to  the  ninth  days  an  average  evening  tem- 
perature of  103°  to  105°  F.  might  be  expected. 

In  favorable  cases  the  fever  begins  to  decline  on  the  ninth,  tenth,  or 
eleventh  day  or  a  little  earlier  or  later.  In  severe  cases  it  may  be 
postponed  until  the  fourteenth,  fifteenth,  or  sixteenth  day.  In  desperate 
cases  the  fever  may  rise  to  great  height  about  this  period. 

A  day  or  so  before  the  subsidence  of  the  fever  it  is  not  rare  to  observe 
striking  irregularities  in  the  temperature  curve.  This  precritical  disturb- 
ance is  sometimes  characterized  by  a  pronounced  rise  n  the  temperature 
to  105°  or  106°  F.,  and  in  oiher  cases  by  a  fall  to  normal  or  thereabouts. 
There  is,  however,  a  rapid  rebound  and  the  fever  shortly  afterward 
permanently  abates.  The  fall  in  the  temperature  commonly  begins  in 
the  evening  and  continues  during  the  night.  Critical  declines  may  occur 
in  some  cases,  the  temperature  dropping  to  normal  in  the  course  of 


Pig.  90 


Case  of  typhus;  gradual  decline  of  temperature.    Recovery  (Doty). 


twelve  hours;  more  commonly,  however,  there  is  a  step-like  descent, 
requiring  two,  three,  or  four  days  to  reach  the  normal  line.  It  is  seen, 
therefore,  that  the  fever  more  often  declines  by  lysis  than  by  crisis. 
(Fig.  91.) 

In  fatal  cases  it  is  not  rare  to  note  a  preagonic  hyperpyrexia.  Wunder- 
lich  observed  a  temperature  of  109.4°  F.  just  before  death. 

Pulse. — The  frequency  of  the  pulse  in  typhus  fever,  under  ordinary 
circumstances,  is  proportionate  to  the  intensity  of  the  accompanying 
pyrexia.  In  this  respect  and  in  the  rarity  of  dicrotism  it  differs  from  the 
pulse  of  typhoid  fever.  In  moderately  severe  cases  the  pulse  rate  in  the 
evenings,  during  the  first  week,  varies  from  110  to  120.  At  this  time 
the  pulse  is  full  and  of  good  volume,  but  later  becomes  softer  and  more 
compressible.  Dicrotism  is  occasionally  observed  during  the  second 
week,  but  is  distinctly  rarer  than  in  typhoid  fever.  In  severe  cases, 
as  the  disease  progresses,  the  pulse  becomes  rapid,  feeble  and  small, 


Tffl':  HYMPTOMATOIJKIY  Oh'  TYI'iniH  FEVKIt 


)7!) 


and  frequently  intermittent.  Patients  may  lie  for  a  number  of  days  with 
the  pulsations  scarcely  palpable  at  the  wrist. 

The  cardiac  sounds  are  clear  and  of  good  tone  early  in  the  disease, 
but  later,  especially  in  severe  attacks,  give  evidence  of  myocardial 
change.  They  may  become  weak  and  distant  and  the  first  sound 
almost  inaudible.  When  this  develops  with  accompanying  cyanosis  of 
the  face  and  extremities  acute  dilatation  of  the  heart  is  to  be  expected. 

The  Typhus  Rash  or  Exanthem. — The  eruption  of  typhus  fever  is  so 
uniformly  present  and  so  characteristic  of  the  disease  as  to  warrant  the 
inclusion  of  typhus  in  the  list  of  exanthematous  affections.  It  may 
in  rare  cases  be  absent,  and  in  others  so  poorly  defined  as  to  escape 
observation.    It  has  been  estimated,  however,  that  it  is  seen  in  95  per 


Fig.  91 


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Case  of  typhus ;  decline  of  temperature  by  crisis.    Recovery  (Doty). 

cent,  of  all  cases.  It  is  one  of  the  most  conspicuous  and  diagnostic 
symptoms  of  the  disease,  a  fact  which  has  led  to  the  use  of  such  desig- 
nations as  "spotted  fever,"  "petechial  fever,"  etc. 

The  exanthem  usually  makes  its  appearance  upon  the  fourth  or  fifth 
day  of  the  disease,  but  may  occur  as  early  as  the  second  and  as  late  as 
the  eleventh  day.  Salamon,  working  with  Curschmann,  observed  the 
rash  in  39  cases  of  typhus;  of  this  number,  it  appeared  11  times  on  the 
fourth  day,  13  times  on  the  fifth  day,  and  5  times  on  the  seventh  day. 

The  spots  appear  first  upon  the  abdomen,  chest,  shoulders,  and  back; 
very  soon  they  make  their  appearance  upon  the  arms  and  legs,  even  as 
far  as  the  hands  and  feet.  The  face  is  usually  entirely  free  of  eruption, 
although  in  children  at  times  the  rash  may  be  sufficiently  pronounced 
to  cause  confusion  with  measles. 

The  lesions  are  not  very  abundant  upon  the  first  day,  but  constantly 


580  TYPHUS  FEVER 

increase  in  number  for  about  forty-eight  hours,  when  the  full  complement 
of  spots  is  present. 

The  rash  is  made  up  of  two  elements — a  background  consisting  of  a 
poorly  defined,  violaceous  reticulation,  the  so-called  "subcuticular 
mottling,"  and  the  rose  spots  or  maculae.  The  macules  are  pinhead 
to  lentil-seed  sized,  pale  red  or  rosy-red  at  the  onset,  with  ill-defined 
borders  and  scarcely  elevated  above  the  surface  of  the  skin.  In  some 
cases  the  mottling  may  be  present  without  the  spots,  but  the  converse 
of  this  is  seldom  the  case.  In  the  beginning  the  macules  disappear 
completely  upon  pressure,  but  gradually  the  color  becomes  more  dusky 
or  actually  purplish  and  the  discoloration  can  no  longer  be  made  to 
fade  under  tension  or  pressure.  The  bluish  or  purplish  coloration  is 
evidence  of  hemorrhagic  extravasation  into  the  skin.  At  times,  late 
in  the  course  of  the  disease,  petechise  may  develop  upon  healthy  areas 
of  the  skin  without  the  previous  presence  of  macules. 

Only  a  certain  proportion  of  rose  spots  become  the  seats  of  hsemic 
extravasation.  In  general  it  may  be  stated  that  the  greater  the  extent 
of  hemorrhage  into  the  skin,  the  more  severe  is  the  attack.  Petechial 
spots  are  most  commonly  seen  about  the  flexures  of  joints,  particularly 
the  groin,  and  on  dependent  portions  of  the  cutaneous  surface,  such 
as  the  back. 

The  duration  of  the  eruption  varies  according  to  the  amount  of  dermic 
hemorrhage.  Simple  rose  spots  may  disappear  in  a  day  or  two;  those 
showing  moderate  extravasation  fade  in  five  or  six  days,  while  deep 
purplish  petechise  may  persist  for  two  or  three  weeks. 

During  the  process  of  fading  the  spots  pass  through  the  color  grada- 
tions of  blood  pigment,  showing  themselves  as  greenish,  yellowish,  or 
brownish  stains.  The  disappearance  of  the  eruption  is  commonly 
followed  by  a  branny  or  furfuraceous  scaling. 

The  individual  lesions  of  the  typhus  eruption  in  the  beginning  bear 
a  strong  resemblance  to  those  of  typhoid  fever.  They  are,  however, 
less  papular,  more  abundant,  and  later  petechial  in  character.  The 
macules  are,  at  times,  more  abundant  upon  the  extremities  than  upon 
the  trunk,  a  circumstance  that  is  never  observed  in  typhoid  fever; 
indeed,  in  the  latter  disease  spots  upon  the  arms  and  legs  are  quite 
unusual. 

In  exceptional  cases  the  rash  of  typhus  may  be  absent,  constituting 
the  so-called  typhus  sine  exanthemate.  Murchison  failed  to  discover 
a  rash  only  55  times  in  2499  cases. 

Spleen. — The  spleen  appears,  according  to  Curschmann,  to  be 
moderately  enlarged  in  the  majority  of  cases  of  typhus.  The  enlarge- 
ment begins  usually  from  the  third  to  the  fifth  day  and  is  determinable 
by  palpation.  The  splenic  swelling  does  not  last  long,  but  subsides 
usually  with  the  decline  of  the  fever.  This  explains  the  negative  results 
that  have  been  noted  in  autopsies,  the  swelling  having  disappeared  before 
death. 

Subcutaneous  Lymphatic  Glands. — ^The  subcutaneous  lymphatic  glands 
are    ordinarily  not   enlarged.     In  some  epidemics    the  inguinal    and 


77//';  SYMPTOM  ATOr/)flY  OF  TV  I'll  UH  f<'/<:VEH  581 

axillary  f^laiids  have  been  observed  to  undergo  inflammation  and  sup- 
puration. The  parotid  and  submaxillary  glands  may  become  tumefied 
either  early  or  late  in  the  course  of  the  disease. 

Nervous  System.— Psycliic  disturbances  in  typhus  fever  are  among 
the  most  conspicuous  and  constant  manifestations  of  the  disease. 
Indeed,  the  word  typhus  is  derived  from  a  Greek  term  signifying  stupor. 
Early  in  the  disease  the  nervous  phenomena  play  a  prominent  role  in 
the  symptom-complex. 

Headache,  intense  restlessness,  and  insomnia  are  seen  in  nearly  all 
cases.  The  cephalalgia  is  intense  and  persistent,  seldom  abating  before 
the  appearance  of  the  exanthem,  and  frequently  not  until  the  end  of 
the  first  week.  Inability  to  sleep  is  a  distressing  symptom  and  one 
difficult  to  relieve;  it  often  continues  up  to  the  critical  period,  when  the 
patient  falls  into  a  refreshing  slumber.  Giddiness  and  noises  m  the 
ears  commonly  accompany  the  early  headache;  the  former  is  rendered 
manifest  when  the  patient  assumes  the  erect  position  or  even  when  he 
sits  up  in  bed. 

Consciousness  is  preserved  during  the  early  days  of  the  disease,  but 
there  is  a  dulling  of  the  mental  faculties.  The  patient,  though  listless 
and  apathetic,  is  able  to  pertinently  answer  questions  addressed  to  him. 

Gradually,  however,  the  intellect  becomes  clouded,  perception  is  slow, 
meiliory  fails,  and  confusion  reigns  supreme.  The  patient  loses  knowl- 
edge of  his  surroundings  and  lapses  into  a  semistuporous  condition 
from  which  he  can  be  but  partially  aroused. 

As  would  be  naturally  expected,  the  headache,  rachialgia,  and  other 
subjective  disturbances  gradually  disappear  as  the  psychic  faculties  are 
obtunded. 

Delirium  is  a  prominent  symptom  of  the  disease  and  usually  manifests 
itself  during  the  latter  half  of  the  first  week.  It  varies  greatly  in  its 
character,  depending  much  upon  the  temperament  of  the  patient  and 
the  nature  of  the  psychic  impulses  which  he  experiences.  At  times  it 
is  of  a  muttering  character,  the  patient  talking  incessantly  in  a  low  tone 
between  his  half -closed  teeth.  The  sufferer  frequently  imagines  himself 
in  the  performance  of  his  usual  duties  and  his  conversation  and  actions 
will  be  governed  accordingly. 

Delusions  of  persecution  are  commonly  experienced;  the  patient  is 
suspicious  of  nurse,  physician,  and  attendants;  he  refuses  food  for  fear 
it  is  poisoned.  He  is  apprehensive  of  all  sorts  of  imaginary  dangers, 
and  may  as  a  result  attempt  to  make  his  escape,  preferring,  as  a  rule, 
the  window  as  an  avenue  of  egress.  In  other  cases  the  patient  may 
experience  terrorizing  hallucinations,  and  become  aroused  to  the  highest 
degree  of  maniacal  excitement.  Under  the  influence  of  these  insane 
impulses  self-destruction  may  be  attempted  or  aggressive  assault  may 
be  made  upon  the  attendants. 

Cases  are  on  record  in  which  patients  have  leaped  headlong  from 
windows  in  their  suicidal  endeavors.  The  greatest  vigilance  is  necessary 
on  the  part  of  the  attendants  in  the  care  of  patients  suffering  from 
this  disease. 


582  TYPHUS  FEVER 

In  severe  cases  the  delirium  terminates  in  coma,  which,  in  fatal  cases, 
becomes  progressively  more  profound.  The  tongue  and  hands  are 
tremulous  and  there  is  twitching  of  the  muscles  and  picking  at  the  bed- 
clothes. When  coma-vigil  develops  the  patient  is  in  a  most  desperate 
state;  the  patient  neither  sees  nor  hears,  although  the  eyes  are  wide 
open  and  staring  fixedly  into  space. 

In  rare  cases  epileptiform  convulsions  are  observed,  the  patient 
lapsing  into  coma  after  the  subsidence  of  the  convulsive  movements. 
This  only  occurs  in  the  worst  cases  and  is  usually  associated  with  the 
presence  of  considerable  albumin  in  the  urine. 

In  cases  .terminating  fatally  there  is  a  progressively  deepening  coma 
from  which  the  patient  cannot  be  aroused.  The  patient  is,  of  course, 
unable  to  swallow;  urine  and  feces  are  passed  involuntarily;  the  pulse 
becomes  rapid,  feeble,  and  intermittent;  the  respirations  hurried  and 
shallow,  and  death  takes  place  from  exhaustion. 

Most  writers  refer  to  a  disturbance  of  hearing,  beginning  usually 
toward  the  end  of  the  first  week  and  amounting  in  some  cases  to  complete 
deafness.  Curschmann  claims  that  auditory  disturbances  do  not  make 
their  appearance  until  the  period  of  convalescence,  when  they  become 
comparatively  frequent. 

He  ascribes  the  deafness  not  to  the  action  of  the  toxin  on  the  auditory 
centres,  but  to  a  catarrhal  otitis  media  which  at  times  ends  in  abscess 
of  the  middle  ear,  with  perforation. 

Gastrointestinal  Tract. — The  tongue  in  the  beginning  is  covered  with 
a  thick,  whitish  fur;  later  it  becomes  dry  and  brown.  During  the 
comatose  state  it  is  commonly  hard  and  leathery  and  covered  with  dried 
blood  which  issues  from  the  fissures.  The  mucous  membrane  of  the 
mouth  and  lips  is  likewise  dry  and  covered  with  sordes. 

Thirst  and  anorexia  are  common  symptoms  at  the  onset  of  the  disease. 
Vomiting  is  not  common,  but  occasionally  occurs  during  the  period  of 
invasion.  In  rare  cases  it  may  be  repeated  and  accompanied  by  epi- 
gastric pain. 

Constipation  is  the  rule  in  nine-tenths  of  the  cases  during  the  first 
week.  Later  in  the  disease  diarrhoea  may  set  in  and  stools  may  be 
passed  involuntarily.  It  is  associated  with  meteorism  and  some  abdom- 
inal tenderness.  Loose  movements  are  believed  by  many  physicians  to 
be  due  to  the  liquid  diet  upon  which  the  patients  are  kept.  The  stools 
do  not  possess  the  distinctive  character  of  the  typhoid-fever  dejecta. 

Respiratory  Tract.- — A  catarrhal  condition  of  the  entire  respiratory 
tract,  but  especially  the  bronchial  tubes,  is  so  commonly  seen  in  typhus 
fever  as  to  belong  properly  to  the  symptomatology  of  the  disease. 

This  process  involves  the  nasopharynx,  larynx,  trachea,  and  bronchial 
tubes  to  their  smallest  ramifications. 

Bronchitis. — Bronchitis  is  usually  present  during  the  first  week;  the 
cough  is,  as  a  rule,  slight  and  accompanied  by  little  or  no  expectoration. 
In  the  second  week  the  bronchitis  may  become  more  widespread,  and, 
through  involvement  of  the  terminal  bronchioles,  lead  to  atelectasis  or 
bronchopneumonia. 


COMPLWA  TIONS  A  ND  S/<JQUEL^  583 

Hypostatic  Congestion-  TTyposfjiiic  ron^cstion  of  thn  liin/]j.s  is  not 
uricoinmoii  owing  to  the  recumbent  position  in  which  tlie  patient 
persistently  lies. 

Bronchopneumonia. — lironchopnenmonia  and  lobar  j)nonmonia  are 
common  couiplications  and  are  not  infrcfjnently  overlooked  owing  to 
the  gravity  of  the  more  conspicuous  symptoms.  In  addition,  pain, 
cough,  and  expectoration  may  be  slight  or  absent.  Lividity  of  the  face 
and  an  increase  in  respiratory  frequency  are  suspicious  .symptoms.  The 
lungs  should  be  carefully  auscultated  from  time  to  time  to  fliscover 
pneumonia  or  hypostatic  congestion  in  their  incipiency. 

Lobular  or  lobar  pneumonia  is  a  frequent  cause  of  death,  particularly 
in  some  epidemics. 

Laryngitis. — Laryngitis  is  present  quite  commonly  and  gives  rise  to 
hoarseness  and  at  times  aphonia.  Ordinarily  this  is  due  merely  to  a 
catarrhal  inflammation  of  the  laryngeal  mucous  membrane.  In  severe 
cases  erosions  and  ulcerations  may  occur  and  lead  to  perichondritis  and 
necrosis  of  the  thyroid  cartilage. 

Kidneys  and  Urine. — The  urine  in  typhus  fever  does  not  present  any 
characteristics  peculiar  to  the  disease.  As  is  the  case  in  other  febrile 
infectious  diseases,  the  urine  is  of  high  color  and  specific  gravity  and 
shows  an  increase  in  the  amount  of  urea  and  other  solid  organic  con- 
stituents. 

In  cases  with  high  fever  a  moderate  febrile  albuminuria  is  observed 
during  the  height  of  the  pyrexia.  This  may  be  accompanied  by  the 
presence  of  a  few  hyaline  casts. 

True  parenchymatous  nephritis,  evidenced  by  pronounced  albumin- 
uria, epithelial  and  hyaline  casts,  and  at  times  blood,  is  fortunately  an 
uncommon  complication. 

In  15  cases  of  typhus,  the  urine  examined  throughout  the  course  of 
the  disease  is  said  by  Buchanan^  to  have  shown  the  presence  of  albumin 
in  but  2  cases.  Morales,  cited  by  Lic^aga,  made  200,  analyses  of  the 
urine  and  found  albumin  frequently.  He  furthermore  noted  the 
presence  of  peptone,  urobilin,  and  the  biliary  acids.  On  the  fifth  day  of 
the  disease  hyaline  casts  and  pigment  granules  were  commonly  found. 

COMPLICATIONS  AND   SEQUEL.ffl;. 

In  addition  to  bronchopneumonia,  nephritis,  otitis  media,  etc.,  which 
were  referred  to  under  the  head  of  symptomatology,  there  are  other 
complications  which  occur  from  time  to  time  during  the  course  of 
typhus  fever. 

Bed-sores. — Bed-sores  are  not  infrequently  observed  in  dependent 
areas  subjected  to  pressure.  Curschmann  found  this  complication 
present  in  about  3  per  cent,  of  his  cases.  The  supine  position  constantly 
maintained  by  typhus  patients  favors  the  development  of  a  necrosis 
of  the  skin  over  the  back,  particularly  in  the  region  of  the  sacrum. 

1  Article  on  Typhus,  Reynolds'  System  of  Medicine. 


584  TYPHUS  FEVER 

Gangrene. — Gangrene  of  the  skin,  particularly  of  terminal  members, 
such  as  the  toes,  ears,  and  fingers  has  been  noted  by  a  large  number  of 
physicians.  When  gangrene  of  the  lower  extremities  develops,  there 
are  pain  and  numbness  in  the  limbs,  followed  by  a  lowering  of  the 
temperature  of  the  affected  parts.  The  pulsations  in  the  arteries  cease 
and  the  toes  begin  to  exhibit  a  livid  hue,  which  later  becomes  purplish 
and  finally  black.  The  skin  and  subjacent  tissues  become  hard  and 
dry  and  mummification  sets  in.  A  line  of  demarcation  may  form  and 
spontaneous  amputation  result,  or  surgical  removal  may  become 
necessary.  In  some  cases  the  sphacelation  may  take  the  form  of  a  moist 
gangrene. 

Noma. — Noma,  or  cancrum  oris,  occasionally  develops  in  the  course 
of  typhus  fever,  as  it  does  in  some  other  exanthemata. 

The  terminal  gangrene  above  referred  to  is  doubtless  due  to  an 
arteritis  with  the  formation  of  arterial  thrombi.  When  the  veins  of  the 
legs  are  attacked,  with  the  production  of  a  phlebitis,  the  affected  mem- 
bers become  hot  and  swollen  and  take  on  the  ordinary  appearance  of 
a  phlegmasia  alba  dolens. 

Erysipelas. — Erysipelas  is  a  complication  much  spoken  of  by  the 
older  writers,  but  it  is  much  less  common  at  the  present  day  owing  to 
the  better  hygienic  conditions  which  prevail  in  modern  hospitals. 

Boils. — Boils  and  subcutaneous  abscesses  are  met  with  more  fre- 
quently in  some  epidemics  of  typhus  than  in  others.  They  develop,  as 
a  rule,  during  the  convalescent  stage,  which  may  be  as  a  result  thereof 
prolonged. 

Parotitis. — Parotitis  appears  to  be  one  of  the  most  frequent  com- 
plications of  typhus.  It  is  encountered  with  unusual  frequency  in 
certain  epidemics.  Schilling,  of  New  York,  in  1852,  observed  it  in  about 
20  per  cent,  of  his  cases.  This,  to  be  sure,  is  an  unusually  high  incidence. 
The  inflammation  niay  come  on  at  any  stage  of  the  disease,  but  most 
commonly  during  the  third  week.  One  or  both  sides  may  be  affected. 
In  the  majority  of  cases  the  inflamed  gland  goes  on  to  suppura  ton.  In 
some  cases  the  submaxillary  salivary  glands  enlarge  and  undergo  abscess 
formation.  These  abscesses  add  considerably  to  the  gravity  of  the  disease. 

Jaundice. — Mild  attacks  of  jaundice  are  not  rare  in  the  course  of 
typhus  fever;  in  some  epidemics  the  icterus  has  been  so  intense  as  to 
suggest  the  existence  of  some  other  disease  with  hepatic  disturbance. 

Other  Complications.— Local  or  general  paralysis,  gangrene  of  the 
lungs,  and  suppuration  of  the  joints  might  also  be  mentioned  as  among 
the  rare  complications  of  typhus  fever. 

Temporary  Insanity. — Temporary  insanity  in  one  of  its  various 
forms  has  been  known  to  persist  for  some  time  after  convalescence 
from  typhus.  Roupefl  mentions  the  case  of  a  woman,  aged  twenty-two 
years,  who  suffered  from  mania  and  who  was  confined  in  a  lunatic 
asylum  for  several  months  after  convalescence  from  the  disease,  ulti- 
mately making  a  complete  recovery  from  the  mental  aberration. 

Duration  of  the  Disease  and  Variations  in  the  Course.— The  ma- 
jority of  writers  are  in  accord  that  the  duration  of  typhus  fever  under 


COMPfJCATfONS  AND  Sl'XjfJKL/E  F)Hr) 

ordinary  circumstances  is  about  fourteen  days.  It  is  not  rare  for  the 
disease  to  run  a  course  of  one  or  two  days  longer  than  this  period,  or, 
on  the  other  hand,  to  terminate  a  day  or  two  Ijcfore  the  fortnight  is 
completed. 

It  is  uncommon  for  the  fever  to  persist  in  unconi[)licatcd  cases  after 
the  eighteenth  day  and  distinctly  rare  after  the  end  of  three  weeks. 
Lebert  says  that  he  has  exceptionally  seen  "the  duration  of  the  disease 
prolonged  to  five  or  six  weeks,  not  merely  by  complications,  but  also 
by  protracted  convalescence  of  a  slight  febrile  character." 

Curschmann  has  observed  cases  beginning  with  marked  hyperpyrexia 
run  an  unusually  protracted  course  to  a  fatal  termination.  Under  such 
circumstances,  the  fever,  very  high  in  the  beginning,  may  fall  to  normal 
or  below,  where  it  may  continue  for  some  days  or  a  week  before  death 
takes  place.  A  fatal  termination  may  be  delayed  to  the  end  of  the 
second  or  the  middle  of  the  third  week. 

Various  authors  have  described  cases  of  typhus  of  unusual  malignancy 
which  terminated  fatally  in  a  few  days;  this  form  of  the  disease  was 
designated  typhus  siderans  by  the  older  writers.  The  symptoms,  in 
brief,  are  a  severe  chill,  rapid  rise  of  temperature  to  great  height,  repeated 
vomiting,  severe  cephalalgia  and  general  pains,  frequent  small  pulse, 
and  rapid  clouding  of  the  mental  faculties.  The  spleen  is  found  to  be 
distinctly  enlarged  in  these  cases.  The  eruption  is  wholly  or  in  part 
suppressed.  Death  may  supervene  in  the  course  of  two  or  three  days, 
and  in  rare  cases,  it  is  said,  even  within  a  day  or  two  after  the  onset  of 
the  disease. 

Hemorrhagic  Typhus  Fever. — Hemorrhagic  typhus  fever  is  an 
excessively  rare  variety.  The  invasive  symptoms  are  of  great  severity 
and  are  followed  about  the  third  day  by  hemorrhagic  extravasation 
into  the  skin  in  the  form  of  petechise  and  larger  ecchymoses.  In  addition 
hemorrhages  occur  into  the  conjunctivae  and  from  the  various  mucous 
surfaces — from  the  mouth,  nose,  kidneys,  uterus,  intestines,  etc. 

There  is  pronounced  cardiac  weakness,  profound  prostration,  and,  in 
some  cases,  gangrenous  complications.  These  cases  exhibit  a  striking 
parallelism  with  that  form  of  hemorrhagic  smallpox  know^n  as  purpura 
variolosa. 

Under  the  heading  of  abortive  cases  of  typhus  fever,  Curschmann 
describes  attacks  characterized  by  a  violent  chill  followed  by  a  rise 
in  temperature,  which  reaches  its  maximum  in  twenty-four  to  thirty-six 
hours.  For  several  days  the  pyrexia  persists  as  a  continued  or  continued- 
remittent  fever,  then  declining  rapidly  by  crisis  to  the  normal  line, 
where  it  remains.  In  these  cases  the  fever  may  have  run  its  course  by 
the  fifth  or  sixth  day  or  earlier.  The  accompanying  s\Tnptoms  may  be 
severe  and  alarming,  even  after  the  temperature  begins  to  fall. 

The  rash  in  these  cases  is  usually  scanty  and  of  short  duration.  In 
those  cases  in  which  it  is  absent  the  diagnosis  may  be  rendered  extremely 
difficult  and  at  times  impossible. 

Writers  have  referred  to  different  varieties  of  typhus  fever  under 
such  names  as  inflammatory  typhus,  ataxic  t^'phus,  adynamic  typhus, 


586  TYPHUS  FEVER 

etc.  These  designations  and  many  others  have  been  used  to  classify 
certain  expressions  of  the  disease,  but  as  they  tend  rather  to  compKcate 
than  to  clear  one's  comprehension  of  typhus  they  might  well  be  permitted 
to  become  obsolete. 


THE  DIAGNOSIS  OF  TYPHUS  FEVER. 

Although  there  is  no  pathognomonic  symptom  which  distinguishes 
typhus  fever  from  other  diseases,  yet  the  symptom-complex  is  suffiiecntly 
distinctive  and  well  defined  to  render  the  diagnosis  clear  in  the  vast 
majority  of  cases. 

The  mode  of  onset,  the  rapid  rise  of  fever  to  its  maximum,  the  early 
development  of  pronounced  cerebral  symptoms,  the  peculiar  facies,  the 
characteristic  rash,  and  the  nature  of  the  pyrexial  curve  collectively 
bespeak  a  disease  which  can  be  trenchantly  separated  from  all  other 
infectious  maladies. 

Typhoid  Fever. — It  is  only  within  the  last  half-century  that  typhus 
has  been  clearly  distinguished  from  typhoid  or  enteric  fever.  Excep- 
tionally, individual  cases  still  arise  in  which  the  differential  diagnosis  is 
difficult,  but  under  ordinary  circumstances  these  two  diseases  should 
not  be  confounded. 

Typhus  and  typhoid  fever  prevail  under  different  conditions,  and 
spread  in  a  different  manner.  The  former  is  endemic  in  certain  countries, 
but  may  reach  other  localities  during  epidemic  prevalence  of  the 
dise^-se.  It  is  distinctly  contagious  and  becomes  disseminated  through 
the  contact  of  the  well  with  the  sick  or  through  the  intermediation  of 
infected  articles.  Typhoid  fever  spreads  in  several  ways,  but  chiefly 
through  a  contaminated  water  supply;  it  is  not  contagious,  at  least 
according  to  the  usual  acceptation  of  this  term. 

An  attack  of  typhoid  fever  is  usually  preceded  by  a  period  of  indis- 
position and  malaise.  Typhus  fever,  in  the  majority  of  cases,  is  ushered 
in  suddenly  and  without  prodromal  illness. 

The  pyrexial  curve  varies  considerably  in  the  two  diseases.  In  typhoid 
fever  there  is  a  step-like  ascent  for  about  a  week,  then  about  a  week 
of  even  temperature,  and  finally  a  gradual  decline  occupying  about  the 
same  period.  The  fever  in  typhus  rises  more  rapidly,  reaches  its 
maximum  about  the  fourth  or  fifth  day,  and  declines  to  normal  by  a 
more  or  less  critical  fall  about  the  end  of  the  second  week.  The  morning 
remissions  are  less  pronounced  than  in  typhoid,  and  the  febrile  course 
is,  with  rare  exceptions,  distinctly  less  protracted. 

The  pulse  of  typhoid  fever  is  in  general  slower  and  more  often  exhibits 
dicrotism  than  the  pulse  of  typhus. 

The  chill,  headache,  pains  in  the  legs,  and  prostration  are  all  more 
intense  in  typhus.  The  nervous  symptoms  come  on  at  an  earlier  date 
and  the  psychic  disturbance,  particularly  the  delirium,  is  more  violent. 
The  flushed  and  oedematous  face,  injected  conjunctivae,  and  general 
wild  expression  of  typhus  patients  contrasts  strongly  with  the  pale, 
depressed  countenance  of  typhoid  patients. 


77//';  DIAdNOHl^  OF  TYf'f/f/S  FFYKIi  587 

The  eruption  of  typhus  develops  earher  (about  the  fifth  flay),  comes 
out  in  one  continuous  crop,  and  is  usually  more  j^rofusc  than  tliat  of 
typhoid  fever.  It  must  be  remembered,  however,  that  the  typhoifj 
exanthem  may  occasionally  be  abundant  and  the  typhus  eruj>fiori 
sparse. 

The  rash  of  typhoid  is  generally  limited  to  the  trunk,  whereas  the 
typhus  spots  involve  the  trunk  and  extremities,  even  to  the  hands  and 
feet.  The  typhoid  spots  come  out  in  separate  crops  and  are  more 
papular  and  have  a  more  defined  border  than  typhus  lesions.  The 
latter,  moreover,  tend  to  become  petechial,  when  they  no  longer  dis- 
appear under  pressure  as  do  the  typhoid  rose  spots. 

Typhoid  fever  is  more  often  accompanied  by  meteorism,  gurgling  in 
the  right  iliac  fossa,  diarrhoea,  and  the  peculiar  pea-soup  stools. 

The  mean  duration  of  typhoid  fever  is  three  weeks  and  of  typhus 
two  weeks.  In  addition  to  the  above  clinical  symptoms,  certain  tests 
are  of  importance.  The  agghitination  reaction  of  Widal  will  aid  in  the 
diagnosis  of  typhoid  fever,  but  not  during  the  early  days.  Eberth's 
bacilli  may  be  recovered  from  the  spleen,  or  from  the  urine,  stools, 
blood,  or  rose  spots.  On  autopsy  Peyer's  patches  will  be  found  to  be 
ulcerated  in  typhoid  fever,  but  not  in  typhus. 

Relapsing  Fever. — The  differentiation  of  typhus  and  relapsing  fever 
may  be  attended  with  great  difficulty,  particularly  during  the  onset  of 
the  disease.  In  both  maladies  the  fever  rises  rapidly  to  great  height. 
Typhus,  however,  is  accompanied  by  much  more  severe  constitutional 
commotion  and  by  greater  mental  disturbance;  in  relapsing  fever  the 
mind  remains  clear  and  the  general  condition  remarkably  good.  Further- 
more, there  is  entire  absence  of  a  cutaneous  eruption.  At  the  end  of 
five  or  seven  days  in  relapsing  fever  the  temperature  subsides  to  normal, 
where  it  remains  for  a  similar  period,  then  rising  and  ushering  in  the 
relapse.  Jaundice  is  observed  in  a  large  number  of  cases.  Examination 
of  the  blood  will  reveal  the  presence  of  the  spirillum  of  Obermeier. 

Malarial  Fever. — In  tropical  countries  and  even  elsewhere  at  times, 
a  malignant  form  of  remittent  fever  is  seen  wdiich  may  in  some  respects 
closely  resemble  typhus  fever.  The  high  fever  is  accompanied  by  great_ 
prostration  and  early  disorder  of  the  mental  faculties.  Later,  manifes- 
tations of  the  typhoid  state  may  make  their  appearance.  Where  doubt 
exists  the  examination  of  the  blood  will  reveal  the  presence  of  the 
hsematozoa  of  malaria  and  the  diagnosis  will  thus  be  rendered  clear. 

Meningitis. — Both  in  idiopathic  meningitis  and  in  the  epidemic 
variety  a  similarity  to  typhus  fever  may  be  presented  through  the 
predominance  of  the  cerebral  s3^mptoms.  Cerebrospinal  meningitis  is, 
moi'eover,  accompanied  by  an  eruption  which  may  lead  to  error.  It  is 
only,  however,  when  the  symptomatology  is  irregular  that  real  diffi- 
culties in  the  diagnosis  are  presented.  In  meningitis  the  headache  is  more 
intense  and  of  a  sharp,  boring  character.  Nausea  and  vomiting,  which 
are  rare  symptoms  in  typhus,  are  apt  to  be  present.  Rigidity  of  the 
muscles  of  the  neck  and  retraction  of  the  head  are  of  great  diagnostic 
importance  in  meningitis.    Later  various  paralyses  develop. 


588  TYPHUS  FEVER 

Pneumonia. — In  certain  forms  of  pneumonia  attended  with  typhoidal 
manifestations  and  masked  pulmonary  symptoms,  there  may  be  a 
resemblance  to  typhus  fever.  The  rash  will  be  absent  and  a  careful 
examination  of  the  chest  will  discover  the  presence  of  consolidation  of 
the  lung. 

Delirium  Tremens. — Typhus  fever  occurring  in  persons  strongly 
habituated  to  the  use  of  intoxicating  liquors  may  present  symptoms 
simulating  mania  a  potu.  Insomnia,  delirium,  and  muscular  tremblings 
may  be  present  in  both  conditions.  The  high  fever,  eruption,  and  course 
of  the  disease  will  readily  distinguish  typhus  fever. 

In  the  eruptive  stage  typhus  fever  may  be  confounded  with  measles, 
with  hemorrhagic  smallpox,  and  with  severe  forms  of  purpura. 

Measles. — During  the  evolution  of  the  eruption,  the  typhus  exanthem, 
particularly  when  it  is  profuse,  with  a  tendency  to  coalescence,  may 
closely  simulate  that  of  measles.  This  is  especially  true  in  the  case  of 
children,  in  whom  it  may  occasionally  appear  upon  the  face.  Roupell 
believes  that  Sydenham  was  probably  dealing  with  an  epidemic  of 
typhus  fever  in  1674  when  he  described  an  anomalous  and  malignant 
form  of  measles.  Sydenham^  says:  "The  measles  of  1674  deviated  from 
rule,  did  not  preserve  their  type;  the  eruption  came  out  irregularly,  was 
often  confined  to  the  neck  and  shoulders.  The  bran-like  desquamation 
did  not  result,  peripneumonia  more  frequently  took  place,  and  in  some 
cases  the  fever  would  last  fourteen  days  or  more. 

Typhus  differs  from  measles  in  many  particulars,  and  may  usually 
be  readily  differentiated.  The  prodromal  stage  of  measles  is  char- 
acterized by  marked  catarrhal  symptoms  giving  rise  to  sneezing  and 
coughing;  the  fever  rises  gradually  and  not  to  such  a  height  as  in  typhus; 
the  face  is  profusely  covered  with  the  rash,  which  spreads  downward 
over  the  trunk  and  extremities.  In  typhus  the  fever  soon  reaches  its 
maximum,  and  the  febrile  course  is  longer.  The  rash  seldom  occurs 
on  the  face,  the  rose  spots  later  exhibit  petechial  change,  and  the 
sensorium  is  more  prof oundly  affected ;  patients  previously  attacked  by 
measles  are  susceptible  to  the  disease. 

.  Smallpox. — The  symptoms  of  the  initial  stage  of  smallpox  and  typhus 
fever  present  a  striking  similarity.  In  each  disease  we  have  chills, 
sudden  high  fever,  headache,  general  pains,  and  profound  prostration. 
Vomiting  is  much  more  frequent  in  variola  than  in  typhus.  The  appear- 
ance of  the  characteristic  eruption  on  the  third  day  after  the  onset  of 
the  fever  in  variola  will  clear  up  the  diagnosis.  Between  purpura 
variolosa  and  hemorrhagic  typhus  fever  a  differentiation  is  often  im- 
possible. Both  are  characterized  by  hemorrhages  into  the  skin  and 
from  the  various  mucous  membranes,  associated  with  intense  prostration 
and  death  in  a  few  days.  The  knowledge  of  the  prevalence  of  one  or 
the  other  disease  will  aid  in  the  diagnosis. 

Purpura. — Severe  cases  of  purpura  hemorrhagica  may  likewise  be 
confounded  with  malignant  typhus  fever.     The  former,  however,  is 

1  Opera,  p.  232. 


77//';  I'liOdNOHIH,  01''  7'V/'II(J.H  FJ'JVJ'JIi 


589 


seldom  ushered  in  with  intense  fever  and  the  prostration  in  the  beginning 
is  not  extreme.  It  is  only  under  exceptional  circumstances  that  a  con- 
fusion of  the  two  diseases  would  take  place. 

THE  PROGNOSIS  OF  TYPHUS  FEVER. 

The  wide  divergence  in  tlie  mortality  rates  of  epidemics  of  typhus 
fever  many  years  ago  is  doubtless  due  to  the  fact  tliat  typhoid  fever, 
relapsing  fever,  and  typhus  fever  were  often  confounded  and  considered 
one  and  the  same  disease. 

The  fatality  of  typhus  is  influenced  by  many  factors,  chief  among 
which  are  the  age  of  the  patient,  his  hygienic  environment,  the  con- 
dition of  his  health  prior  to  the  attack,  and  the  severity  of  the  prevailing 
type  of  the  disease.  These  and  other  influences  will  be  considered 
in  detail. 

Age. — The  age  of  the  patient  influences  the  mortality  to  a  considerable 
extent.  With  the  exception  of  very  young  children  the  disease  is  much  less 
fatal  in  childhood  and  youth  than  in  age  periods  beyond  these.  Beyond 
the  age  of  twenty  years  the  mortality  progressively  increases,  reaching 
its  maximum  in  advanced  old  age.  Below  are  appended  three  series 
of  age  statistics.  In  the  town  of  Greenock,  according  to  Buchanan, 
the  death  rate  was  as  follows: 


Age. 


Mortality. 


Under  10  years 5.0  per  cent. 


10    to 

20      ' 

20     " 

30      ' 

30     " 

40      ' 

40     " 

50      ' 

Over 

50      ' 

8.6 
15.6 
21.5 
42.0 

66.6 


The  death  rates  of  typhus  fever  in  the  London  Fever  Hospital,  during 
a  period  of  two  years  and  including  3506  cases,  have  been  calculated  by 
Murchison  as  follows: 


Age. 

Admitted. 

Died. 

Per  cent 

Under         5  years 17 

3 

17.65 

Between    5  and  10  years 

1S3 

14 

7.65 

10    "    15      " 

363 

18 

4.95 

15    "     20      " 

.    546 

26 

4.76 

20     "     25      " 

495 

47 

9.05 

25    "    30      " 

348 

52 

15.15 

30     "    35      " 

323 

55 

17.02 

35    "    40      " 

270 

89 

32.96 

40    "     45       " 

292 

87 

29.79 

45     "     50      " 

212 

83 

39.15 

50    "     55      "  ■ 

150 

78 

52.00 

55    "     60      " 

100 

51 

51.00 

60     "     65      " 

88 

49 

55.68 

65     "    70      " 

42 

28 

66.66 

70     "    75      " 

24 

17 

70.83 

75     "     SO      " 

6 

5 

83.33 

Over         SO  years  . 

2 

2 

100.00 

Age  unknown 

50 

11 

22.00 

3506 


20.89 


15    ' 

'     20       ' 

20    ' 

'    30       ' 

30    ' 

'    40      ' 

40     ' 

'     50      ' 

50    ' 

'     60      ' 

590  TYPHUS  FEVER 

Guttstadt^  gives  the  figures  for  5545  cases  admitted  into  Prussian 
hospitals  from  1878  to  1880 : 

Age.  Males.                       Females. 

Under       10  years 2.2  per  cent.  3.3  per  cent. 

Between  10  and  15  years 3.0       "  1.5       " 

.  5.2       "  4.5       " 

.  8.2        "  10.1       " 

.  16.0        "  11.2 

.  31.9        "  20.2 

.  43.7        "  35.5 

Over          60  years 57.1        "  45.2       " 

It  will  be  seen  that  while  Guttstadt's  tables  exhibit  lower  mortality 
rates  than  Murchison's,  the  same  general  influence  of  age  is  shown. 

Curschmann  believes  that  the  increasing  death  rate  after  the  age  of 
forty  is  due  to  the  greater  cardiac  weakness  at  this  period  and  to  the 
increased  liability  to  hypostatic  congestion  of  the  lungs  and  other 
pulmonary  complications  as  a  result  thereof. 

Sex. — Sex  appears  to  exert  but  little  influence  upon  mortality.  Murchi- 
son's figures  give  19.67  per  cent,  of  deaths  in  males  and  18.20  per  cent, 
in  females. 

Hygienic  Environment. — The  social  position  and  financial  condition 
of  individuals  influence  to  a  large  extent  the  character  of  their  surround- 
ings. Food,  mode  of  life,  and  domiciliary  environment,  by  modifying 
the  physical,  mental,  and  moral  tone  of  persons,  influence  to  that  extent 
their  general  health  and  resistance  to  disease,  and  also  their  ability  to 
successfully  cope  with  disease  when  stricken. 

The  mortality  of  typhus  fever  is  particularly  high  among  people 
debilitated  by  famine  and  hardship.  Physical  exhaustion,  such  as  occurs 
in  soldiers  and  among  hard-worked  nurses  and  physicians,  doubtless 
accounts  for  the  comparatively  high  mortalities  among  these  classes  of 
patients.  The  overcrowding  and  unhygienic  conditions  which  often 
prevail  in  barracks,  prisons,  and  on  board  ships  increase  not  only  the 
incidence  of  typhus,  but  also  its  mortality. 

Murchison  divided  the  patients  admitted  into  the  London  Fever 
Hospital  into  three  classes,  according  to  their  social  and  financial 
condition : 

Admitted.  Died.  Per  cent. 

1.  Pay  patients "      .        .        94  15              14.89 

2.  Patients  admitted  free,  but  not  classified  as  paupers.    2674  497              18.6 

3.  Paupers 738  204              27.6 

It  is  seen  from  these  figures  that  the  niortality  is  higher  according 
to  the  poverty  of  the  patients.  Murchison  believes,  however,  that  the 
larger  death  rate  among  the  poorer  patients  is  to  be  explained  by  the 
more  advanced  age  of  these  persons.  He  states  that  the  current  opinion 
in  Ireland  is  that  the  disease  is  accompanied  by  a  higher  mortality 
among  the  rich  than  among  the  poor. 

Intemperance  and  Previous  Health  of  Patient. — It  is  no  less  true  of 
typhus  fever  than  of  smallpox  and  other  infections  that  the  disease  is 

'  Quoted  by  Curschmann. 


77//';  I'liOCNO^IH  O/''  7'VI'l/fJS  Fl'JVJ'Jli  591 

particularly  fatal  in  alcoholics.  Prolonged  habits  of  intemperance 
produce  structural  changes  in  tlie  heart,  bloodvessels,  kidneys,  liver, 
and  nervous  system,  and  weaken  the  d(;ferisive  resources  of  the  body 
when  attacked  by  disease.  In  typhus  fever,  as  in  sniallj>ox,  hemorrhagic 
attacks  are  more  common  in  drunkards  than  in  other  individuals. 

The  previous  existence  of  chronic  organic  diseases  or  of  acute  diseases 
unfavorably  influences  the  prognosis  in  typhus  fever,  as  would  naturally 
be  expected.  Debilitating  illnesses  which  lower  the  resisting  power  of 
the  individual,  or  diseases  in  which  the  structural  integrity  of  important 
organs  is  affected,  very  considerably  lessen  the  chances  of  recovery. 

Unfavorable  Symptoms. — Great  intensity  of  any  or  all  of  the  symp- 
toms of  typhus  fever  constitutes  an  unfavorable  condition,  yet  the 
comparatively  brief  course  of  the  disease  renders  it  possible  for  patients 
exhibiting  even  the  most  alarming  symptoms  to  recover. 

High  fever  during  the  invasive  stage  and  the  remaining  days  of  the 
disease,  if  unattended  by  symptoms  hereafter  to  be  mentioned,  need  not 
be  regarded  as  of  specially  unfavorable  significance.  If,  however,  the 
temperature  continues  very  high  during  the  second  week,  it  indicates 
an  attack  of  great  gravity. 

More  important  than  the  temperature  is  the  condition  of  the  heart 
and  the  bloodvessels.  Lic^aga  regards  an  early  disproportion  between 
the  pulse  rate  and  the  temperature  as  a  sign  of  fatal  omen.  A  pulse 
rate  of  over  120  in  the  beginning  of  typhus  fever  should  excite  solicitude. 
But  the  frequency  of  the  pulse  is  not  the  only  factor  to  be  considered. 
The  rhythm,  volume,  and  compressibility  of  the  arterial  pulsations  and 
the  character  of  the  cardiac  sounds  are  of  equal  or  greater  importance. 
Inaudibility  of  the  first  heart  sound  or  irregularity,  rapidity,  or  marked 
compressibility  of  the  pulse  occurring  early  in  the  disease  are  bad 
prognostic  signs. 

The  condition  of  the  nervous  system  offers  valuable  evidence.  Early 
wild  delirium,  persistent  insomnia,  progressively  deepening  stupor, 
subsultus  tendinum,  carphologia,  muscular  twdtchings,  and  convulsions 
are  all  of  evil  portent.  The  occurrence  of  profound  coma  or  coma-vigil 
renders  the  prognosis  hopeless. 

The  presence  of  considerable  albumin  in  the  urine  during  the  early 
days  of  the  disease  indicates  a  grave  infection.  When  blood  and  casts 
are  associated  an  alarming  complication  is  present. 

Pulmonary  complications  are  commonly  the  cause  of  death,  particu- 
larly in  persons  advanced  in  years.  Hypostatic  congestion,  severe  and 
widespread  bronchitis,  and  pneumonia  swell  the  mortality  list.  Cursch- 
mann  includes  marked  meteorism  and  "pinhole  pupils"  among  the 
specially  unfavorable  symptoms. 

The  profusion  of  the  rash  is  of  less  prognostic  import  than  its  special 
characters.  The  early  appearance  of  petechise  and  an  unusual  degree 
of  hemorrhagic  extravasation  into  the  skin  are  grave  signs.  Pronounced 
cyanosis  of  the  skin,  particularly  of  the  face  and  extremities,  indicates 
cardiac  weakness  and  is,  therefore,  an  ominous  manifestation. 

Among  the  favorable  symptoms  are  moderate  intensity  of  the  fever, 


592  TYPHUS  FEVER 

ability  to  sleep,  preservation  of  the  faculties  of  the  mind,  moist  tongue, 
moderate  frequency  of  the  cardiac  pulsations,  and  early  subsidence  of 
the  pyrexia. 

Mortality  Rate. — The  death  rate  of  typhus  fever  varies  considerably 
in  different  epidemics,  but  will  be  found  usually  to  be  in  the  nieghbor- 
hood  of  18  or  20  per  cent.  Murchison  found  that  the  mortality  of  4787 
cases  of  typhus  fever  treated  in  the  London  Fever  Hospital  between 
1848  and  1862  amounted  to  20.89  per  cent.  The  same  author  collected 
the  immense  number  of  18,592  cases  treated  in  London,  Glasgow, 
and  other  cities,  and  calculated  the  mortality  as  18.78  per  cent.  Lebert 
gives  the  general  mortality  in  his  experience  as  15  per  cent.;  Buchanan, 
10  per  cent. ;  and  Curschmann,  23.4  per  cent. 

The  mortality  in  hospitals  is  higher  than  in  private  practice.  This 
may  be  in  part  accounted  for  by  the  larger  percentage  of  grave  and 
moribund  cases  received  in  hospitals. 

In  the  most  severe  epidemics  the  mortality  may  reach  30,  40,  or  even 
50  per  cent.  During  military  campaigns  and  in  famine-stricken  com- 
munities the  death  rate  is  apt  to  be  particularly  high. 

THE  TREATMENT  OF  TYPHUS  FEVER. 

Prophylaxis. — In  the  prevention  of  such  a  disease  as  typhus  fever 
two  lines  of  action  are  to  be  pursued.  It  is  of  paramount  importance 
to  limit  the  infection,  as  far  as  possible,  to  the  first  afflicted  patients. 
This  is  to  be  accomplished  through  isolation  of  the  sick  and  disinfection 
of  all  articles  which  have  come  into  contact  with  the  patients.  If  these 
measures  could  be  carried  out  with  precision  and  certainty,  little  else 
would  be  necessary.  But  epidemics  within  recent  years  demonstrate 
that  even  with  the  employment  of  modern  methods  it  is  impossible  to 
completely  circumscribe  the  infection  of  the  disease.  It  becomes 
necessary,  therefore,  to  remove  all  those  causes  in  a  community  which 
favor  the  development  and  dissemination  of  typhus.  It  has  already 
been  pointed  out  that  the  congregation  of  large  numbers  of  people  in 
closely  crowded  and  poorly  ventilated  quarters  is  a  potent  contributory 
cause  in  the  spread  of  the  disease.  When  the  original  infection  is  intro- 
duced such  conditions  offer  the  most  favorable  opportunity  for  the 
development  of  an  epidemic.  In  countries  in  which  typhus  is  prone 
to  appear,  the  health  authorities  should  prevent  the  concentration  of 
men  in  barracks,  prisons,  lodging  houses,  tenement  houses,  and  the  like. 
When  this  cannot  be  avoided  free  ventilation  of  these  quarters  must 
be  insisted  upon. 

It  is  likewise  desirable  to  control,  as  far  as  possible,  the  movements 
of  beggars  and  vagrants  in  crowded  slum  districts;  it  is  an  oft -repeated 
experience  that  these  persons  serve  as  carriers  of  contagion.  Licdaga 
quotes  Monjares  as  stating  that  the  removal  from  populous  centres  of 
the  crowds  of  beggars  who  swarmed  the  streets  of  San  Luis  Potosi 
caused  the  disappearance  of  an  epidemic  of  typhus  fever  which  pre- 
vailed in  that  town. 


77//';  tiii<:.\tmi<:nt  of  tvi'Ikjh  fkvich  593 

As  typhus  often  follows  in  the  wake  of  fainijK-  iiiifj  warfare,  the  most 
rigid  precautionary  measures  should  he  em})loyed  wlien  these  conditions 
exist.  Proper  camp  sanitation  and  care  as  to  tlie  feeding  and  housing 
of  troops  are  of  great  importance.  This  was  exemplified  in  tlie  Crimean 
War  in  the  relative  freedom  of  the  English  soldiers  as  compared  with 
the  French.  The  English  army,  owing  to  more  stringent  hygienic  con- 
trol, suffered  much  less  from  typhus  fever  than  did  the  French  troops. 

Isolation. — As  is  true  of  all  contagious  diseases,  the  tyj)hus  patient 
must  be  separated  from  other  persons  during  the  entire  periofl  of  his 
illness.  This  can  be  most  effectively  accomplished  by  .sending  him  to 
a  hospital  specially  set  apart  for  the  purpose.  No  one  at  the  present 
day  would  hazard  placing  a  typhus  patient  in  the  wards  of  a  general 
hospital. 

Where  the  patient  must  be  treated  at  his  home,  an  airy  room  in  the 
upper  part  of  the  house  should  be  selected. 

Carpets,  curtains,  and  all  dispensable  furniture  should  be  removed 
from  the  apartment.  A  communicat'ng  room  should  be  occupied  by 
the  nurse  and  likewise  utilized  to  disinfect  all  articles  leaving  the  sick 
apartment.  Over  the  door  communicating  with  the  corridor  should  be 
suspended  a  sheet  wet  with  a  5  per  cent,  solution  of  carbolic  acid  or 
a  1 :  loop  solution  of  bichloride  of  mercury.  Whenever  possible  the 
attendants  and  nurses  should  be  chosen  from  those  who  have  once 
passed  through  an  attack  of  the  disease.  One  attack  of  typhus  fever 
protects  against  a  second  in  the  vast  majority  of  cases.  When  an 
immune  nurse  cannot  be  secured,  the  one  employed  had  better  not 
sleep  in  the  sick-room.  Non-immune  nurses  should  not  be  permitted 
to  go  abroad  among  people,  for  fear  of  spreading  the  disease.  Immunes 
may  be  permitted  this  privilege  only  when  every  precaution  as  to  personal 
cleanliness  and  disinfection  is  taken.  Intercommunication  between  the 
patient  and  members  of  his  family  must  be  strictly  prohibited. 

Disinfection. — The  destruction  of  the  infection  in  all  articles  with 
which  the  patient  has  come  in  contact  is  a  measure  of  the  highest  impor- 
tance. Mention  has  already  been  made  of  the  frequent  transmission  of 
typhus  fever  in  the  body  linen  of  patients.  To  lessen  the  intensity  of 
the  infection  in  these  articles  frequent  bathing  of  typhus  patients  is 
desirable.  The  baths,  which  may  be  sponge  or  plunge  baths,  subserve 
the  double  purpose  of  reducing  temperature  and  lessening  the  dissemi- 
nation of  the  contagium  of  the  disease. 

The  body  and  bed  linen  should  be  changed  once  or  twice  a  day. 
They  should  be  received  into  an  appropriate  receptacle  containing  a 
5  per  cent,  solution  of  carbolic  acid  or  a  1 :  2000  solution  of  bichloride 
of  mercury. 

The  bodily  excretions  should  be  disinfected  with  chloride  of  lime 
or  one  of  the  above-mentioned  antiseptics.  While  there  is  no  con- 
vincing proof  that  the  infection  of  typhus  is  resident  in  the  dejecta, 
the  disinfection  of  the  stools  and  urine  is  a  wise  and  easily  carried  out 
precaution.  Eating  utensils  should  be  thoroughly  boiled  before  being 
permitted  to  leave  the  sick-apartments. 

3S 


594  TYPHUS  FEVER 

The  physician  in  attendance  upon  typhus  patients  should  protect 
his  clothing  by  wearing  a  long  gown  and  a  cap  which  covers  as  much 
of  his  hair  as  possible.  On  leaving  the  patient  he  should  carefully  wash 
his  face. and  hands  and  air  himself  thoroughly  before  seeing  another 
patient. 

After  the  recovery  of  the  typhus  patient  the  apartments  occupied 
should  be  thoroughly  fumigated  with  formaldehyde  or  sulphur  and 
subsequently  aired  for  a  number  of  days  before  occupancy.  Walls 
should  be  whitewashed,  painted,  or  repapered  according  to  desire. 
Blankets  and  mattresses  should  be  subjected  to  superheated  steam  or 
hot  air  in  the  disinfecting  plant  provided  by  most  large  cities.  When 
such  facilities  are  not  available,  blankets  should  be  boiled  and  mattresses 
burned  and  destroyed. 

Wooden  furniture  should  be  washed  with  a  solution  of  carbolic  acid 
or  bichloride  of  mercury.  The  patients'  clothing  should  be  disinfected 
by  formaldehyde,  steam,  or  hot  air. 

When  death  occurs  the  body  should  be  enveloped  in  a  sheet  saturated 
with  a  carbolic  acid  or  corrosive  sublimate  solution.  An  hermetically 
sealed  casket  should  be  used  and  interment  should  be  private. 

Ventilation. — Ventilation  is  a  preventive  measure  which  appears  to 
be  of  greater  value  in  typhus  than  in  other  disease.  That  the  free 
admixture  and  circulation  of  fresh  air  in  the  sick-apartment  or  ward 
lessens  the  danger  of  contagion  is  admitted  by  all  writers.  Lebert  says 
he  found  it  an  excellent  plan,  even  during  the  severest  cold  of  winter, 
to  keep  the  windows  open  part  of  the  day  and  night;  he  adds  that  the 
patients  bear  cold  well  during  the  continuance  of  fever,  but  are  sensitive 
to  it  later. 

When  epidemics  occur  in  the  summer  months  it  is  a  good  plan  to 
treat  the  patients  in  tents.  The  liability  of  attendants  contracting  the 
disease  under  these  conditions  is  distinctly  lessened. 

The  temperature  of  the  sick-apartments  should  be  in  the  neighborhood 
of  65°  F.  The  floor  is  to  be  mopped  with  an  antiseptic  solution  and 
the  atmosphere  kept  free  from  dust. 

Nursing.' — The  nursing  of  typhus  fever  is  of  great  importance  and 
requires  the  services  of  a  trained  person.  The  body  surface  should  be 
frequently  sponged  with  water  containing  a  little  alcohol  or  with  a 
weak  carbolized  solution.  The  teeth  and  oral  cavity  require  careful 
attention  from  the  beginning;  mild  antiseptic  mouth  washes  should  be 
employed.  Diluted  Dobell's  solution,  boric  acid  water,  or  a  diluted 
peroxide  of  hydrogen  may  be  used.  The  cleansing  of  the  mouth  is  of 
particular  importance  when  the  patient  is  stuporous,  as  the  mucous 
membrane  becomes  dry  and  covered  with  mucus  and  blood  crusts. 

Careful  attention  is  necessary  to  prevent  the  development  of  bed- 
sores. Frequent  ablutions  of  parts  subjected  to  pressure  and  soiled 
by  excretions,  and  the  use  of  pads  or  pneumatic  cushions  to  relieve 
pressure,  will  accomplish  the  object  desired. 

Diet. — The  diet  is  the  same  as  that  prescribed  in  the  other  acute 
exanthemata.     During  the  intense  febrile  period  the  patient  will  desire 


77//!,'  Tkf'JATMI'JNT  OF  TV  I'll  US  I'l'lVKIi.  695 

nothinjTj  hut  li((ni(]  iiotirislimont.  Milk  ;ukI  hroflis  iriay  Ik-  ^ivcn  every 
two  or  three  hours.  As  soon  as  the  j)atient  cures  for  soft  foods  he  may 
be  allowed  to  have  soft-boiled  eggs,  gelatin,  gruels,  milk-toast,  and  like 
foods.  As  the  disease  al)ates  and  the  appetite  incTeases,  a  gradual 
return  to  the  usual  dietary  may  be  begun.  For  tlie  relief  of  thirst 
lemonade  and  the  carbonated  waters  may  be  given.  The  diet  need 
not  be  as  rigid  as  in  typhoid  fever,  in  which  disease  the  presence  of 
intestinal  ulceration  necessitates  great  caution. 

Medical  Treatment.— Although  numerous  remedies  have  been 
advocated  from  time  to  time  for  their  beneficial  action  upon  typhus 
fever,  it  must  be  admitted  that  we  know  of  no  drug  which  materially 
affects  the  course  of  the  disease.  When  the  specific  cause  of  typhus  is 
discovered  a  specific  cure  for  the  disease  may  be  forthcoming.  The 
most  approved  treatment  of  typhus  is  that  which  is  devoted  to  an  alle- 
viation of  the  symptoms  and  the  maintenance  of  the  patient's  strength. 

Fever. — The  fever  in  typhus  often  reaches  a  great  height  and  calls  for 
measures  to  reduce  its  intensity.  Almost  exclusive  reliance  is  to  be 
placed  upon  hydrotherapy  in  one  form  or  another.  In  the  milder  cases 
it  may  suffice  to  employ  tepid  sponge  baths  several  times  a  day.  The 
application  of  an  ice-bag  or  Leiter's  coil  to  the  head  is  a  useful  supple- 
mentary measure.  When  sponge  baths  are  not  sufficient  to  control 
the  pyrexia  recourse  may  be  had  to  the  wet  pack,  the  sheet  being  wrung 
out  of  tepid  or  cold  water  according  to  the  intensity  of  the  fever.  The 
continuous  tepid  or  warm  bath  will  be  found  to  control  the  temperature 
in  a  most  satisfactory  manner;  the  patient  may  be  kept  for  twenty-four 
hours  or  longer  in  a  bath  the  temperature  of  which  is  maintained  between 
93°  and  98°  F.  When  the  graduated  bath  is  employed  the  water  is  at 
first  warm,  but  is  gradually  lowered  by  the  addition  of  cold  water  to 
75°  or  70° F. 

The  Brand  method  of  cold  bathing  so  extensively  adopted  in  the 
treatment  of  typhoid  fever  does  not  seem  to  have  been  systematically 
tried  in  typhus  fever,  although  its  main  features  are  referred  to  in 
favorable  terms  by  those  experienced  in  the  treatment  of  typhus.  With 
one  or  other  of  the  above  hydrotherapeutic  measures  it  will  be  found 
possible  to  control  excessive  fever.  It  should  be  remembered  that  the 
reduction  of  fever  by  these  measures  is  merely  one  of  the  objects  desired. 
Baths  exert  a  tonic  influence  upon  the  respiratory  and  circulatory 
centres  and  allay  nervous  excitability. 

The  coal-tar  antipyretics  should  not  be  used  except  in  very  moderate 
doses.  Wlien  given  in  large  doses  or  over  a  long  period  of  time  they 
may  produce  serious  cardiac  depression.  Phenacetin,  antipyrin,  and 
lactophenin  are  among  the  most  eligible  of  these  preparations. 

Nervous  Symptoms. — Headache  is  commonly  so  persistent  and 
distressing  as  to  require  remedies  for  relief.  The  light  in  the  room 
should  be  kept  subdued  in  order  to  lessen  retinal  irritation.  An  ice-bag 
should  be  applied  to  the  head,  and  bromide  of  sodium,  phenacetin,  or 
antipyrin  administered.  When  these  remedies  fail  to  control  the 
cephalalgia  it  may  be  necessary  to  give  opium. 


596  TYPHUS  FEVER 

Insomnia.— Inability  to  sleep  is  a  bitter  complaint  of  typhus  patients 
during  the  early  days  of  the  disease.  It  is  well  to  first  try  the  bromide 
of  sodium  in  20-grain  doses,  repeated  once  or  twice  during  the  night. 

In  other  cases  chloral  appears  to  do  well,  but  should  not  be  used  in 
large  doses  for  fear  of  depressing  the  heart.  Ten  grains  may  be  admin- 
istered in  the  evening,  and  followed  later  by  a  15-grain  dose  if  necessary. 
Where  sleep  cannot  be  otherwise  obtained  it  is  proper  to  give  a  hypo- 
dermic injection  of  morphine.  The  employment  of  a  warm  or  tepid 
bath  at  the  sleeping  hour  will  often  materially  aid  in  quieting  nervous 
excitement  and  inducing  sleep. 

Delirium. — The  bromides,  chloral,  and  opium  may  be  employed  to 
quiet  excessive  cerebral  activity.  The  best  result  in  many  cases  is 
obtained  by  an  ice-bag  to  the  head  and  a  prolonged  warm  bath,  or,  when 
the  temperature  is  very  high,  a  cold  bath  or  pack. 

Constipation. — In  the  constipation  which  usually  exists  early  in  the 
disease  calomel  in  fractional  doses  may  be  given  or  a  mild  saline  may  be 
used.  One  of  the  disadvantages  of  employing  opium  in  typhus  is  the 
aggravation  of  the  existing  constipation.  When  there  is  much  fever 
a  cold,  high  enema  will  serve  a  double  purpose.  Vomiting,  when  present, 
may  be  controlled  by  pellets  of  ice,  carbonated  or  lime  water,  and 
temporary  abstention  from  food.  The  late  diarrhoea  is  best  checked 
by  bismuth  internally,  and  starch-water  and  laudanum  enemata. 
Meteorism  may,  when  mild,  be  relieved  by  laxatives,  and  turpentine 
internally  and  externally.  Severe "  gaseous  distention  occurring  late  is 
a  grave  symptom,  often  defying  all  treatment. 

Alcohol. — Alcohol  is  a  remedy  of  great  value  in  the  treatment  of 
typhus,  when  it  is  used  with  discrimination.  It  should  not  be  employed 
as  a  routine,  but  rather  to  combat  special  symptoms.  Many  patients 
will  not  require  its  use  at  all.  Buchanan  says  that  alcohol  is  needed  in 
two  classes  of  patients — those  who  cannot  take  a  sufficient  quantity  of 
nourishment,  and  those  habituated  to  the  use  of  stimulants.  He  enumer- 
ates the  special  indications  as  follows:  Alcoholic  stimulants  are  most 
serviceable  in  (1)  old  people;  (2)  in  cases  of  great  prostration  with  low 
delirium  and  coma;  (3)  where  the  pulse  is  very  compressible  and  the 
first  heart  sound  feeble;  also  when  the  pulse  is  rapid  or  irregular;  (4) 
where  the  extremities  are  cold  and  the  surface  livid;  (5)  where  there 
is  much  congestion  of  the  lungs;  (6)  where  there  is  any  erysipelatous 
complication. 

It  may  be  given  in  the  form  of  whiskey,  brandy,  or  wine,  or,  as  Cursch- 
mann  prefers,  in  Stokes'  cognac  mixture,  the  formula  of  which  is  as 
follows : 

Ji— Cognac  opt., 

Aquse  dest oa    15  ounces. 

Vitelli  ovi No.  1. 

Syrupi 6  ounces. 

Tablespoonful  every  two  or  three  hoars. 

When  the  pulse  becomes  compressible,  rapid,  or  irregular,  or  when 
the  first  heart  sound  is  weak,  it  may  be  necessary  to  resort  to  other 
cardiac  stimulants  in  addition  to  alcohol.     Strychnine,  digitalis,  stro- 


77//';  tii[<:atmi<:nt  of  tyi'Iius  fhyku  r,u7 

phanthus  and  cafl'eine  may  he  employed  with  advantage.  Nitroglycerin 
and  camphor  dissolved  in  olive  oil  may  he  used  hypf)deririieally  to  tide 
over  critical  moments. 

Pulmonary  and  renal  (•oTri|)hc;Uions  are  to  he  treated  in  the  same 
manner  as  when  these  conditions  arise  indej)endently. 

In  conclusion  a  v^^ord  of  caution  should  be  uttered  concerning  the 
necessity  for  constant  vigilance  on  the  part  of  the  nurses  and  attendants 
to  prevent  suicidal  or  lioniici(hd  attempts  during  maniacal  excitement. 


CHAPTER    XI L 

DIPHTHERIA. 

Definition. — Diphtheria  is  an  acute  infectious  disease  characterized 
by  the  production  of  a  fibrinous  exudate  or  false  membrane  on  certain 
parts  of  the  mucous  surface  of  the  body.  The  regions  by  far  most 
commonly  involved  are  the  tonsils,  the  pillars  of  the  fauces,  the  soft 
palate,  the  uvula,  the  pharynx,  and  the  nares.  Not  infrequently  the 
disease  extends  into  the  larynx;  or  it  may  begin  there  primarily  and 
remain  limited  to  this  locality.  Except  at  the  onset,  or  when  there  is 
laryngeal  involvement,  febrile  reaction  is  not  a  prominent  symptom. 

The  disease  is  caused  by  a  specific  micro-organism  and  begins  as  a 
local  affection,  but  becomes  systemic  as  the  result  of  absorption  of 
toxins  elaborated  by  the  specific  bacilli  and,  perhaps,  certain  associated 
bacteria.  In  severe  cases  the  toxaemia  may  be  extreme.  After  the 
general  symptoms  have  disappeared,  paralysis  is  liable  to  follow.  This 
may  be  limited  to  a  few  muscles,  or  there  may  be  complete  ataxia. 

History. — Of  the  various  diseases  belonging  to  the  infectious  group, 
which  have  prevailed  from  time  to  time  in  epidemic  form,  diphtheria 
is  believed  to  be  one  of  the  oldest.  Some  writers  have  sought  to  prove 
that  it  was  known  at  the  time  of  Hippocrates,  and  described  under  the 
name  of  Malum  vEgyptiacum.  While  in  the  absence  of  suflBcient 
literature  on  the  subject  this  cannot  be  determined  definitely,  yet  it  is 
true  that  Aretseus,  a  Greek  physician  of  Cappadocia,  who  lived  in  the 
latter  part  of  the  first  and  the  beginning  of  the  second  century,  portrayed 
the  critical  features  of  this  malady  in  language  which  warrants  the 
belief  that  the  disease  he  described  was  diphtheria.  He  speaks  of  a 
thick,  white,  moist  material  which  forms  over  the  tonsils  and  spreads 
over  other  parts  of  the  mouth;  of  ulcers  which  appear  on  the  tonsils, 
and  which  may  be  superficial  and  benignant,  or  extensive,  putrid,  and 
malignant,  according  as  the  case  is  mild  or  severe.  In  malignant  cases 
the  foetor  from  the  mouth  is  loathsome.  Fluids  are  sometimes  regurgi- 
tated through  the  nose  in  the  effort  of  swallowing,  the  voice  is  husky, 
and  when  the  disease  extends  into  the  air  passages  death  speedily  results 
from  suffocation.  He  mentions  that  the  disease  is  most  common  among 
children.  Aretseus  believes  that  this  malady  originated  in  Egypt,  Syria, 
and  especially  in  Coele,  Syria;  hence  the  name  of  Malum  ^gyptiacum. 
It  was  also  known  by  the  name  of  Egyptian  and  Syrian  Ulcerations. 

During  the  fourth  century  a  disease  presenting  the  same  symptoms 
prevailed  in  epidemic  form  in  Rome,  and  was  described  by  Macrobius. 
From  this  time  forward  for  several  centuries  there  seems  to  be  a  paucity 
of  literature  upon  the  subject;  this  may  possibly  mean  that  there  was 
a  long  lapse  of  epidemic  prevalence  of  the  disease. 


DII'll'I'III'llilA  509 

In  the  sixtecntli,  sevciitctuitli,  and  (M^litcciitli  (•(•rlfllri(^s  (;[)i'leirii(.'.s  of 
a  disease  presentui<:j  tin;  (isscntial  cliaracterislics  of  dijjiitlieria  arc  said 
to  have  prevailed  frequently,  and  often  with  great  virulence  in  many 
parts  of  Europe,  particularly  in  Holland,  Spain,  Italy,  France,  and 
Germany.  The  affection  apj)eared  also  in  England,  and  was  described 
by  Fothergill,  Iluxham,  and  others.  In  Sy)ain  the  flisease  was  known 
by  the  name  of  fregar  when  confined  to  the  fauces  or  the  cavity  of  the 
mouth,  but  when  it  appeared  in  the  laryn.x  and  caused  suffocation  it 
was  called  garotillo.  In  the  different  countries  in  which  the  disease 
appeared  it  was  described  by  tlie  physicians  under  various  names, 
such  as,  besides  those  already  mentioned,  cynanche  maligna,  cynanche 
contagiosa,  angina  mahgna,  angina  gangrjcnosa,  ulcerative  sore  throat, 
malignant  sore  throat,  morbus  suffocans  vel  strangulatorius,  epidemic 
croup,  etc. 

It  is  not  known  exactly  when  this  malady  made  its  appearance  in 
America.  In  1771,  Samuel  Bard,  of  New  York,  published  a  brochure 
entitled,  '^An  Enquiry  into  the  Nature,  Cause,  and  Cure  of  the  Angina 
Sujfocativa,  or  Sore  Throat  Distemper,  as  it  is  commonly  called  by  the 
inhabitants  of  this  City  and  Colony."  In  this  article  a  clinical  descrip- 
tion is  given  of  a  disease  comparable  in  its  essential  features  to  diph- 
theria. It  prevailed  chiefly  among  children  under  ten  years,  and  was 
evidently  infectious.  Bard  says  the  disease  began  as  a  sore  throat, 
which,  upon  examination,  showed  that  the  tonsils  were  swollen  and 
inflamed,  and  presented  a  few  white  specks  which,  in  some  cases, 
increased  so  as  to  cover  the  entire  surface  of  the  tonsils  "with  one 
general  slough."  The  swelling  was  sometimes  so  great  as  to  interfere 
with  deglutition.  In  other  cases  there  was  difficulty  of  breathing,  which 
was  often  of  so  great  a  degree  as  to  threaten  immediate  suffocation. 
In  his  brochure  Bard  speaks  of  an  article  previously  written  by 
Douglass,  of  Boston,  describing  a  new  epidemic  of  an  acute  throat 
affection  which  was  seen  in  that  city,  and  which  was  quite  similar  in 
its  clinical  manifestations  to  the  disease  which  later  appeared  in  New 
York  City. 

It  must  be  said  that  these  clinical  descriptions  by  the  earlier  writers 
were  not  very  exact,  and  that  doubtless  several  diseases  were  not  infre- 
quently included  in  the  same  category.  It  is  safe  to  assume  that  some 
of  the  anginose  affections  other  than  diphtheria,  especially  scarlatina, 
were  not  always  differentiated.  Indeed,  Bard  speaks  of  "inflamed  and 
watery  eyes,  a  bloated  and  livid  countenance,  with  a  few  red  eruptions 
here  and  there  upon  the  face,"  as  being  among  the  earlier  sATiiptoms  in 
many  of  the  cases  that  came  under  his  observation.  Likewise,  Douglass 
characterized  the  disease  he  described  as  "An  Eruptive  Miliary  Fever, 
with  Angina  Ulcusculosia." 

In  regard  to  the  history  of  diphtheria  in  America,  literature  shows 
that  the  peculiar  form  of  sore  throat  described  by  Douglass  was  seen 
about  1735  in  certain  inland  towns  in  New  England,  and  gradually 
spread  westward,  reaching  the  locality  of  the  Hudson  River  two  years 
later.    The  disease  prevailed  more  particularly  in  towns  to  which  people 


600  DIPHTHERIA 

resorted  for  trade,  and  was  spread  by  means  of  commercial  intercourse 
and  travel.  In  New  York  an  epidemic  was  noted  by  Father  Middleton 
in  1752.  After  Bard's  description  of  the  disease  in  1771  very  little 
seems  to  have  been  said  about  its  presence  in  New  York  until  1826. 
From  1855  to  1858  it  prevailed  in  some  parts  of  the  State,  especially  in 
Albany,  with  great  malignancy. 

In  1856  Dr.  J.  V.  Fourgeand  published  a  monograph  on  a  terrible 
ep  demic  of  sore  throat  which  occurred  in  San  Francisco  and  other 
towns  of  California. 

An  epidemic  of  a  similar  affection  occurred  in  Philadelphia  as  early 
as  1809.  Again  in  1831  another  epidemic  prevailed.  The  records  of 
the  Health  Office  of  Philadelphia,  however,  do  not  show  that  any 
deaths  occurred  in  this  city  from  "diphtheria"  until  1860,  during 
which  year  the  number  reached  307.  From  the  preceding  historical 
facts  it  is  quite  evident  that  diphtheria  was  not  a  newly  imported  disease 
in  Philadelphia  in  1860,  but  that  it  previously  prevailed  under  other 
names. 

The  earliest  accurate  observations  on  the  clinical  manifestations  of 
diphtheria  were  made  by  Bretonneau,  of  Tours,  in  1821,  when  he 
presented  his  first  celebrated  paper  on  the  subject  to  the  French  Academic 
de  M^decine.  This  paper,  it  is  said,  was  not  published  until  1826. 
The  name  he  suggested  for  the  disease  was  Le  Di'phtherite,  or  Diphther- 
itis.  He  gave  it  this  name  because  of  its  essential  characteristic,  namely, 
the  formation  of  a  false  membrane.  Subsequently  the  name  diphtheria 
was  proposed  by  Trousseau.  This  title,  as  Flint  suggests,  has  the 
negative  merit  of  not  involving  any  hypothesis  as  to  the  pathology  of 
the  affection.  Bretonneau,  however,  believed  that  the  membranous 
exudate  itself  constituted  the  pathological  criterion  for  the  disease ;  that 
an  inflammation  without  an  exudation  is  not  a  diphtheritis,  neither  is 
an  inflammation  with  an  exudation  when  it  is  not  infectious.  In  other 
words,  he  not  only  regarded  the  exudate  as  an  essential  part  of  the 
disease,  but  also  as  constituting  the  only  source  of  the  infection.  He 
believed  the  contagium  spread,  not  through  the  atmosphere,  but  by 
inoculation,  as  it  were,  resulting  from  particles  of  the  exudate,  either 
in  a  fluid  or  dust-like  state,  coming  in  immediate  contact  with  the  moist 
mucous  membrane. 

Bretonneau's  observations,  which  were  quite  extensive,  led  him  to 
conclude  that  membranous  croup  and  diphtheria  were  identical  affec- 
tions ;  the  only  difference  being  that  in  croup  the  disease  process  extended 
into  the  larynx  and  trachea.  He  at  first  fell  into  the  error  of  regarding 
diphtheria  as  wholly  a  local  disease,  but  later  frankly  admitted  that 
systemic  poisoning  was  an  essential  pathological  condition.  Angina 
gangrsenosa,  he  declared,  is  in  no  way  related  to  this  affection. 

Trousseau  with  his  acute  power  of  clinical  observation  directed 
attention  to  the  difference  between  diphtheria  and  some  of  the  throat 
affections,  especially  scarlatina,  with  which  it  was  often  confounded, 
and  also  pointed  out  the  danger  of  this  disease  from  its  liability  to  extend 
into  the  air  passages.     The  fact  that  death  not  infrequently  resulted 


i>ii'iri'iii<:itiA  00] 

at  an  early  period  of  the  diseast;  from  an  adynamic  conrlition  wa.s 
observed  by  him  and  e,s])ecially  commented  upon,  lie  is  credited  with 
rendering  vahiable  assistance  to  Bretonneau  in  establishing  the  operation 
of  tracheotomy  for  tli(>  r(;lief  of  membranons  croup;  even  th(;  inriications 
given  by  liim  for  its  adoption  woidd  still  s(!rve  as  a  useful  guide  for  u.s 
at  the  present  day. 

Recognizing  that  the  disease  was  primarily  local,  Jiouchut  recom- 
mended the  removal  of  hypertrophied  tonsils  when  covered  with  an 
exudate,  with  the  object  of  preventing  the  membrane  from  extending 
downward  into  the  larynx  and  trachea.  He  was  the  first  to  practise 
"tubage"  of  the  larynx  for  relief  of  the  stenosis  caused  by  membranous 
croup. 

This  procedure,  however,  was  condemned  and  fell  into  disuse  for 
nearly  a  quarter  of  a  century,  when,  in  1880,  it  was  revived  and  brought 
to  a  high  state  of  perfection  by  O'Dwyer,  of  New  York.  Intubation  is 
now  almost  universally  regarded  as  an  indispensable  auxiliary  in  the 
treatment  of  membranous  croup. 

After  Bretonneau's  publication  appeared  diphtheria  was  recognized 
and  described  by  the  physicians  of  every  civilized  country,  and  there 
soon  developed  a  wealth  of  literature  upon  the  subject.  Many  excellent 
works  were  published  by  French,  German,  and  English  waiters.  There 
w^ere,  however,  some  conflicting  notions  regarding  the  nature  of  the 
disease.  Some  maintained  that  it  began  as  a  general  systemic  infection, 
entirely  independent  of  any  previously  existing  local  affection.  In  other 
words,  the  exudate  was  regarded  as  a  local  expression  of  a  constitutional 
disease,  manifesting  itself  by  preference  upon  the  mucous  membrane 
of  the  fauces,  just  as  the  rash  of  scarlet  fever  does  upon  the  skin.  This 
view  was  opposed  by  most  of  the  ablest  writers,  and  in  the  light  of  our 
present  knowledge  is  regarded  as  untenable. 

The  question  about  which  there  was  perhaps  the  greatest  difference  of 
opinion  was  whether  diphtheria  and  membranous  croup  were  identical 
affections,  or  whether  they  constituted  two  distinct  morbid  processes. 
It  may  truly  be  said  that  physicians  of  the  present  day  are  not  yet 
entirely  agreed  on  this  question.  Bretonneau,  Wagner,  and  many  others 
contended  that  no  clinical  or  pathological  distinction  between  these 
diseases  could  be  made,  while  Virchow  threw  the  w^eight  of  his  authority 
on  the  opposite  side  of  the  question.  This  distinguished  pathologist 
sought  to  establish  an  anatomopathological  distinction.  He  believed  he 
had  succeeded  in  showing  that  in  the  croupous  form  of  inflammation 
the  exudation  is  deposited  upon  the  surface  of  a  sound  mucosa,  while 
in  diphtheritic  inflammation  the  exudation  takes  place  into  the  very 
substance  of  the  mucosa  as  well  as  upon  its  surface,  and  that  this  mem- 
brane undergoes  interstitial  necrosis  from  want  of  nourishment  caused 
by  compression  of  the  bloodvessels.  This  attempt  to  distinguish  between 
membranous  croup  and  diphtheria  has  been  unsuccessful,  and  the 
leading  clinicians  and  pathologists  now  admit  their  specific  identity. 

The  consideration  of  diphtheria  has  assumed  a  new  phase  since 
bacteriology  has  become  so  important  a  hand-maiden  to  the  clinician. 


602  DIPHTHERIA 

The  study  of  micro-organisms  in  their  relation  to  this  disease  dates 
back  over  a  period  of  many  years,  even  more  than  a  quarter  of  a  century. 
In  1868,  Oertel,  together  with  Buhl  and  Hueter,  discovered  bacteria 
in  the  false  membrane,  the  blood,  and  in  certain  tissues  of  patients, 
which  he  believed  sustained  a  causal  relation  to  the  disease.  He 
described  these  organisms  as  presenting  various  forms,  such  as  spherical, 
rod-like,  and  corkscrew-shaped.  They  were  also  demonstrated  by 
von  Recklinghausen,  Nassiloff,  Waldeyer,  Klebs,  Eberth,  Heiberg,  and 
others.  While  these  investigators  were  evidently  working  along  the 
right  lines,  and  may  have  seen  the  specific  bacillus,  yet  they  failed  to 
differentiate  it  from  its  associates. 

The  credit  of  discovering  the  true  bacillus  of  diphtheria  belongs  to 
Klebs,  of  Zurich.  It  is  generally  stated  that  this  discovery  was  made 
in  1883,  but  Lennox  Browne  makes  the  following  statement  in  reference 
thereto:  "Professors  Hamilton  and  Sternberg  have  drawn  attention  to 
its  discovery  by  the  same  observer  (Klebs),  and  to  publication  of  the 
fact  at  a  congress  held  at  Wiesbaden  so  far  back  as  the  year  1875. 
The  circumstance  appears  to  have  attracted  but  little  attention,  notwith- 
standing that  on  examination  of  the  original  reference  it  is  found  that 
Klebs  had  announced  at  this  date  that  he  had  not  only  detected  the 
bacillus,  but  that  he  had  also  made  an  effort  to  cultivate  it,  and,  as  far 
as  one  can  judge,  successfully.  To  Klebs,  therefore,  the  credit  of  having 
discovered  this  organism  is  undoubtedly  due.  But  since  he  never 
definitely  announced  that  he  had  been  able  to  obtain  pure  cultures  of  it, 
it  must  be  said  that  he  failed  in  establishing  its  causal  relationship  to 
the  disease." 

This  relationship  was  later  established  in  1884  by  LoeflQer,  who 
succeeded  not  only  in  obtaining  pure  cultures  of  the  bacillus,  but  also 
in  proving  its  specific  character  by  communicating  diphtheria  to  guinea- 
pigs  and  birds  by  inoculating  them  with  this  organism.  Hence,  through 
the  combined  labor  of  these  two  investigators,  in  discovering  and 
establishing  the  specificity  of  this  micro-organism,  it  is  known  by  the 
name  of  Klebs-Loeffler  bacillus.  This  discovery  has  had  the  effect  of 
settling  the  long  and  often  animated  controversy  as  to  whether  diph- 
theria is  primarily  a  constitutional  or  local  affection  in  favor  of  the 
latter,  and  has  placed  the  study  of  the  disease  on  a  scientific  basis. 

THE  ETIOLOGY  OF  DIPHTHERIA. 

In  considering  the  causation  of  diphtheria  in  the  light  of  our  present 
knowledge  it  might  be  thought  sufficient  to  give  simply  a  description 
of  the  Klebs-Loeffler  bacilli  and  the  associated  bacteria,  with  an  explana- 
tion of  their  causative  relation  to  the  local  and  systemic  manifesta- 
tions of  the  disease.  This  is  the  course  pursued  by  many  writers  of 
the  present  day.  But  while  it  is  impossible  to  convey  a  correct  knowl- 
edge of  the  etiology  of  diphtheria  without  carefully  describing  its  bac- 
teriology, yet  for  a  comprehensive  understanding  of  the  subject  it  is 
necessary  also  to  consider  the  predisposing  causes  as  well  as  the  means 


77//';  I'VriOIJXIY  f>F  DII'IITIIHIilA  603 

by  which  the  disease  may  l)e  disseminated,  and  tfie  (■onditions  favrjrable 
for  its  spread. 

The  disease  is  (lontagious.  While  sporadic  cases  may  be  met  with,  yet 
when  it  once  obtains  a  foothold  in  a  community  it  is  j>artionlarly  prone 
to  assume  an  epidemic  character.  The  evidence  of  its  infectiousness 
is  very  conchisive.  When  diphtheria  appears  in  a  family  it  frequently 
attacks  many  members  in  succession.  The  fact  that  some  meml^ers  of 
the  family  often  escape  is  no  evidence  that  it  is  not  contagious,  for  this 
not  infrequently  hap})ens  with  scarlet  fever,  the  contagiousness  of  which 
no  one  doubts.  In  regard  to  such  instances  it  may  be  said  that  ever  so 
little  positive  evidence  outweighs  any  number  of  negative  facts.  Further 
evidence  of  its  contagious  nature  is  found  in  the  fact  that  physicians  and 
nurses  in  attendance  upon  cases  very  frequently  contract  the  disease. 
In  the  Municipal  Hospital  of  Philadelphia  most  of  the  resident  7>hysicians 
who  have  worked  in  the  diphtheria  wards  have  suffered  from  the  disease 
in  variable  degrees  of  severity.  In  one  instance  the  attack  was  so  severe 
that  death  resulted  at  an  early  stage.  The  majority  of  the  nurses  have 
shown  symptoms  more  or  less  marked  soon  after  beginning  work 
in  the  wards.  It  is  not  unusual  for  physicians  and  nurses  who  have 
been  in  attendance  upon  cases  in  private  practice  to  be  admitted  to  the 
hospital  suffering  from  the  disease. 

Not  infrequently  diphtheria  has  been  communicated  by  direct  contact 
with  detached  pieces  of  exudate  or  the  secretions  from  the  throat  and 
nose  of  patients.  We  have  known  nurses  to  show  symptoms  of  the 
disease  within  forty-eight  hours  after  having  had  coughed  into  their 
faces  some  of  the  infectious  material  from  the  throats  of  patients.  We 
have  likewise  known  infection  to  result  from  kissing.  ]\Iore  than  one 
physician  has  fallen  a  victim  to  diphtheria  through  his  zealous  efforts 
to  save  the  life  of  a  patient  by  clearing  out  an  obstructed  tube  after 
tracheotomy  by  suction,  or  by  trying  to  inflate  the  lungs  after  the  oper- 
ation by  blowing  his  own  breath  into  them  through  a  tube.  Oertel  says: 
"In  this  way  Otto  Weber,  Seehusen,  Valleux,  Blache,  Cillite,  fell 
sacrifices  to  their  professional  devotion.  Dr.  Wiessbauer,  of  Munich,  lost 
his  child,  who  had  a  short  t'me  previous  to  its  death  unfortunately  gotten 
hold  of  a  cannula  and  put  it  in  its  mouth,  the  cannula  having  just  been 
removed  from  a  patient  sick  with  diphtheria."  Still  further  evidence 
that  the  disease  is  infectious  is  found  in  the  fact  that  it  has  been  com- 
mvmicated  to  some  of  the  lower  animals  experimentally  by  inoculation. 

It  is  well  known  that  diphtheria,  like  all  contagious  diseases,  some- 
times occurs  sporadically,  at  other  times  endemically,  and  then  again 
epidemically.  In  attempting  to  explain  these  circumstances  one  must 
take  into  consideration  not  alone  the  causa  causans,  or  the  specific  germ 
of  the  malady,  but  also  the  causa  efjiciens,  or  that  which  determines  the 
occurrence  of  widespread  epidemics.  In  studying  the  latter  it  is  neces- 
sary to  enquire  into  the  sanitary  surroundings  of  each  particular  locality 
where  the  disease  prevails,  and  into  all  conditions  which  may  influence 
individual  receptivity  to  the  infection,  such  as  climate,  domestic  environ- 
ment, age,  sex,  rainfall,  season,  etc. 


604  DIPHTHERIA 

Geographical  Distribution. — No  country  can  be  said  to  be  absolutely 
exempt  from  diphtheria,  although  it  prevails  to  a  much  greater  extent 
in  some  places  than  in  others.  The  disease  has  invaded  both  hemi- 
spheres, and  it  has  occurred  in  the  northern  and  southern  portions  of 
each.  Altitude  seems  to  exert  but  little  influence  over  its  spread,  as  it 
has  been  found  in  both  high  and  low-lying  countries.  According  to 
statistics  of  the  United  States,  however,  it  has  caused  the  greatest 
proportion  of  deaths  in  the  Southern  Central  Appalachian  region,  the 
Central  Appalachian  reigon,  and  the  region  of  the  Western  plains; 
while  the  proportion  of  deaths  was  least  in  the  South  Atlantic  coast 
region  and  the  Gulf  coast  region. 

The  disease  occurs  in  the  higher  degrees  of  latitude ;  but  of  all  localities 
it  is  most  common  in  the  temperate  zone  and  that  part  of  the  frigid  zone 
immediately  adjacent  thereto,  and  least  common  in  the  tropics.  The 
records  of  India  show  that  it  is  rare  in  the  tropical  climate  of  that 
country;  nor  does  it  thrive  anywhere  in  the  tropical  parts  of  Asia. 
It  is  also  rare  in  Central  and  South  America. 

Conditions  of  the  Soil.' — Some  writers  have  ascribed  to  the  soil  a 
certain  influence  over  the  propagation  of  the  disease.  It  was  a  common 
impression  among  the  older  writers,  and,  indeed,  some  of  the  more 
modern  still  hold  to  the  opinion,  that  low,  damp  soil,  such  as  is  found 
in  marshy  regions  with  bad  drainage,  especially  near  rivers  which 
frequently  overflow  their  banks  and  where  there  is  a  good  deal  of 
vegetable  matter  undergoing  decomposition,  favors  the  development  of 
diphtheria;  while,  on  the  other  hand,  a  high,  dry  soil,  or  a  soil  composed 
largely  of  dry  sand  has  been  regarded  as  unfavorable  to  the  spread 
of  the  disease.  At  least,  some  observers  claim  that  it  appears  less 
frequently  and  is  less  likely  to  be  disseminated  in  localities  characterized 
by  the  latter  geological  conditions. 

While  it  is  recognized  that  for  the  production  and  propagation  of 
diphtheria  the  presence  of  the  specific  micro-organism  must  be  regarded 
as  a  sine  qua  non,  yet  it  is  not  improbable  that  these  organisms  may 
thrive  under  certain  conditions  and  perish  under  others.  Whether  soil 
in  any  of  its  forms  exerts  any  such  influence  one  way  or  the  other  is 
uncertain.  At  times  it  does  appear  as  though  such  an  influence  was 
especially  marked,  yet  statistics  show  that  the  disease  has  occurred 
and  even  prevailed  in  epidemic  form  in  districts  where  the  local  con- 
ditions were  regarded  as  unfavorable  for  its  spread. 

According  to  Lennox  Browne,  epidemics  of  diphtheria  in  England 
"have  been  very  catholic  in  their  distribution  from  both  the  geographical 
and  the  geological  aspect."  But  an  interesting  table  compiled  by  him 
seems  to  justify  the  belief  that  the  disease  has  a  decided  preference 
for  a  clayey  soil.  This  table  bears  out  the  opinion  of  Dr.  Thorne  Thorne, 
whom  he  quotes  as  saying  that  "where  a  surface  soil  is,  by  reason  of  its 
physical  constitution  and  topographical  relations,  such  as  to  facilitate 
the  retention  of  moisture  and  of  organic  refuse,  and  where  a  site  of  this 
character  is,  in  addition,  exposed  to  the  influence  of  cold  and  wet  winds, 
there  you  have  conditions  which  tend  to  the  fostering  and  fatality  of 


77//';  F/riOLOdY  OF  DII'irrilFiilA  OOo 

diphtheria,  and  also  go  to  determine  the  specific  (juality  of  local  sore 
throat."  The  marked  predilection  of  the  disease  for  wet,  clayey  soils  ha,s 
been  commented  upon  by  many  writers,  some  of  whom  have  yjointed  out 
that  diphtheria  is  not  only  more  common  but  more  fatal  in  localities 
with  wet  and  retentive  soils  than  in  those  with  dry  and  pervious  grounrl 
conditions. 

Evidence  could  be  cited  tending  to  show  that  the  disease  is  fostered 
by  decomposing  heaps  of  manure  and  vegetable  refuse,  such  as  are 
found  about  stables  where  sheep,  cattle,  and  other  animals  are  kept. 
Outbreaks  of  diphtheria  have  been  reported  where  this  condition 
existed  in  close  proximity  to  dwelling-houses.  The  drainage  from 
decomposing  animal  and  vegetable  matter  imparts  to  the  soil  a  .serious 
contamination.  The  digging  up  of  old  drains,  especially  those  connected 
with  dwelling-houses,  has  been  followed  more  than  once  by  an  outbreak 
of  diphtheria.  Surely  the  upturning  of  soil  thus  polluted  is  a  fertile 
source  of  diphtheroid  sore  throats,  or  pseudodiphtheria,  if  not  of  the 
true  disease  itself.  At  any  rate  it  cannot  be  denied  that  the  emanations 
from  such  a  source  act  as  a  predisposing  cause  to  precipitate  an  attack 
when  the  diphtherial  entity  is  present. 

Rainfall. — The  question  as  to  whether  the  annual  amount  of  rainfall 
exerts  any  influence  over  the  prevalence  of  diphtheria  or  its  mortality 
has  not  been  positively  determined.  Statistics  have  been  cited  to  prove 
both  the  positive  and  negative  sides  of  the  question,  and  are,  therefore, 
conflicting.  After  fully  considering  the  evidence  at  hand  we  are  inclined 
to  believe  with  most  writers  that  rainfall  is  not  a  very  important  factor 
in  determining  the  diffusion  of  the  disease. 

Season.^ — Diphtheria  is  undoubtedly  much  more  prevalent  during 
the  cold-weather  months  than  during  the  summer.  This  is  shown  very 
clearly  by  the  statistics  of  all  countries  where  the  disease  prevails,  and 
is  made  especially  clear  in  the  last  census  report  on  vital  statistics  of 
the  United  States.  While  the  returns  of  deaths  in  this  report  are,  for 
obvious  reasons,  incomplete,  yet  they  are  sufficiently  complete  for 
comparative  purposes.  Of  course,  the  number  of  cases  of  diphtheria 
is  not  given,  but  the  number  of  deaths  by  months  may  be  regarded  as 
a  fair  index  of  the  prevalence  of  the  disease  for  the  same  periods. 

The  following  table  shows  for  the  United  States  the  deaths  by  months 
from  diphtheria  in  the  census  year  1900: 

Months.  Deaths.  Months.                                       Deaths. 

January 1816                     July 827 

February 1496                     August 89S 

March 1411  September        ....  1303 

April 115S                     October 1739 

May 1081  November        ....  1912 

June 795  December         ....    1904 

This  table  indicates  that  diphtheria  (including  croup)  is  most  prev- 
alent in  the  United  States  during  the  nine  months  beginning  with 
September  and  ending  with  May,  and  least  prevalent  during  the  summer 
months  of  June,  July,  and  August.  The  three  months  showing  the 
greatest  number  of  deaths  are  November,  December,  and  Januarv. 


606 


DIPHTHERIA 


By  dividing  the  year  into  quarters,  representing  the  four  seasons,  we 
find  the  number  of  deaths  for  each  season  to  be  as  follows:  spring, 
3648;  summer,  2510;  autumn,  4954;  winter,  5246.  The  winter  months, 
and  especially  the  autumn  and  winter  months,  show  by  far  the  greatest 
proportion  of  deaths. 

The  following  table  shows  the  admissions  by  months  of  diphtheria 
patients  into  the  Municipal  Hospital  of  Philadelphia  during  the  last 
decade : 


Year. 

Jan. 

Feb. 

Mar. 

April 

May 

June 

July 

Aug. 

Sept. 

Oct. 

Nov. 

Dec. 

1893  .... 

36 

24 

21 

■J 

16 

24 

7 

13 

5 

21 

26 

17 

1891 

15 

2ii 

33 

.     20 

28 

25 

38 

33 

39 

70 

81 

64 

1895 

65 

65 

66 

46 

56 

54 

68 

61 

38 

48 

66 

73 

1896 

(i2 

54 

67 

48 

74 

60 

44 

45 

66 

86 

122 

141 

1897 

107 

97 

76 

87 

61 

105 

109 

112 

87 

145 

149 

150 

1898 

137 

78 

71 

84 

88 

73 

76 

84 

121 

146 

146 

125 

1899 

117 

72 

81 

83 

109 

103 

94 

139 

110 

123 

178 

164 

1900 

143 

126 

119 

95 

102 

102 

92 

94 

:08 

133 

141 

112 

1901 

101 

87 

98 

97 

80 

76 

47 

53 

66 

62 

53 

69 

1902 

89 

58 

59 

45 

51 

55 

36 
611 

25 

36 

52 

46 

45 

Total 

872 

681 

691 

612 

665 

677 

659 

676 

886 

1008 

960 

This  table  also  shows  that  the  disease  was  most  prevalent  during 
the  months  of  November,  December,  and  January,  and  least  prevalent 
during  the  three  summer  months.  Considering  the  table  as  a  whole, 
the  total  number  of  cases  in  each  of  the  four  seasons  is  as  follows: 
spring,  1968;  summer,  1937;  autumn,  2560;  winter,  3513. 

It  will  be  noticed  here  that  the  autumn  and  winter  months  furnished 
by  far  the  largest  number  of  cases.  This  is  in  accordance  with  the 
observation  of  many  writers.  Newsholme  says:  "Diphtheria  is  most 
prevalent  in  autumn  and  in  the  early  winter  months,  when  the  opti- 
mum temperature  and  the  optimum  degree  of  humidity  of  the  soil  are 
rapidly  disappearing  or  have  departed.  It  is  also  most  prevalent  after 
the  wet  weather,  occurring  in  or  immediately  following  exceptionally  dry 
years.  Both  these  conditions  tend  to  raise  the  ground  water  and  to 
drive  out  any  pathogenic  micro-organisms  from  the  soil." 

The  greater  prevalence  of  diphtheria  during  the  cold -weather  months 
can  be  rationally  explained,  we  believe,  by  the  well-known  observations 
that  the  fauces  and  upper  air  passages  are  then  much  more  liable  to 
attacks  of  catarrhal  inflammation,  thus  affording  an  increased  suscepti- 
bility to  the  disease,  and  that  the  sanitary  surroundings  in  schools  and 
dwelling-houses  at  this  time  of  the  year  are  apt  to  be  at  their  worst. 

Domestic  Environment.— Under  this  head  might  be  included  the 
unsanitary  conditions  of  domestic  life,  such  as  result  from  the  crowding 
together  of  a  large  number  of  people  into  tenement  houses,  narrow 
streets,  courts,  and  alleys,  where,  besides  the  crowding,  the  drainage 
is  bad,  and  the  air  almost  necessarily  impregnated  with  animal  emana- 
tions and  all  kinds  of  foul  odors.  Surroundings  of  this  nature  are  sure 
to  prejudice  health  and  exert  a  definite  influence  in  determining  an 
outbreak  of  diphtheria  and  favoring  its  spread.    It  is  a  matter  of  common 


Till':  F/riOLOCV  of  UWIITIII'IKIA  {]()- 

observation  in  all  i;u-n;e  cities  when;  this  fiisc^ase  is  eiifleniic  that  the 
inhabitants  of  such  localities  sufler  to  the  f^reatest  extent.  While  j^ersons 
who  live  under  more  favorable  circumstances  are  not  spared,  yet  the 
transmission  of  the  infection  is  particularly  favored  by  poverty  and 
uncleanliness. 

Not  alone  do  overcrowded  conditions  of  rlwcllin^-houses  favor  the 
propaf];ation  of  diphtheria,  but  in  all  congested  institutions,  especially 
those  for  the  care  of  children,  in  factories,  schools,  barracks,  and,  in 
short,  wherever  there  is  a  large  aggregation  of  persons  living  under 
unhygienic  environments,  there  the  disease  is  wont  to  break  out  and 
assume  an  epidemic  form.  But,  as  already  stated,  more  favorable 
modes  of  living  do  not  ensure  safety  against  the  ravages  of  the  malady. 
Oertel  very  truly  says:  "Robust  children  who  enjoy  the  best  of  care 
and  nourishment  are  seized  and  carried  off  by  the  disease,  although  the 
number  of  such  cases  does  not  reach  that  attained  in  other  classes,  in 
which  poverty  and  uncleanliness  favor  the  spreading  of  the  pestilence." 
Even  the  rich  and  cultivated  dwellings,  under  the  most  modern  sanitarj- 
improvements  of  ventilation,  plumbing,  drainage,  and  the  like,  have 
furnished  a  fair  quota  of  victims  to  this  fell  destroyer  of  human  life. 
This  shows  that  the  specific  organism  of  diphtheria  is  no  respecter  of 
persons;  nevertheless,  certain  environments  or  conditions  of  life  exert 
a  very  potent  influence  over  the  spread  of  the  disease. 

Dissemination  of  the  Infection. — The  infection  of  diphtheria  is 
commonly  communicated  through  direct  exposure  to  a  person  suffering 
from  the  disease.  The  dust  from  a  sick-room,  contaminated  with 
particles  of  dried  secretions  from  the  throat  and  nose  of  a  patient,  may 
serve  to  convey  the  infection  for  a  short  distance  through  the  agency 
of  the  atmosphere.  The  well  members  of  a  family  in  which  the  disease 
exists  often  unwittingly  carry  the  contagium  to  others.  It  is  frequently 
disseminated,  especially  where  no  attention  is  given  to  disinfection,  by 
means  of  infected  articles,  such  as  clothing,  bedding,  towels,  handker- 
chiefs, carpets,  drapery,  upholstery,  books,  toys,  and  the  like.  It  must 
be  admitted  that  physicians  and  nurses  are  sometimes  the  agencies  of 
transmitting  the  infection.  Even  pet  animals  may  play  a  part  in  this 
baneful  work. 

Doubtless  the  disease  is  often  spread  by  exceedingly  mild  cases — so 
mild,  indeed,  that  the  symptoms  are  not  correctly  interpreted.  Of 
course  no  restrictions  are  placed  on  the  movements  of  persons  thus 
mildly  afflicted.  Adults  continue  at  their  daily  vocation,  and  children 
go  to  school  as  usual.  Such  cases  are  constantly  met  with,  especially 
in  large  cities  where  diphtheria  is  endemic.  It  is  well  known  that  some 
cases  of  chronic  rhinitis  are  really  of  a  diphtheritic  nature,  inasmuch  as 
the  Klebs-Loeffler  bacilli  are  sometimes  found  in  this  disease.  "When 
this  condition  exists,  it  is  frequently  not  recognized,  and  therefore  no 
restrictions  are  enforced,  nor  even  any  precautionary  measures  advised. 
Really,  it  is  a  question  whether  the  mild  and  unrecognized  cases  of 
diphtheria  are  not  much  more  often  responsible  for  the  spread  of  the 
disease  than  the  severe  cases,  for  the  latter  are  usually  surrounded  with 


(308  DIPHTHERIA 

the  proper  sanitary  measures,  such  as  isolation,  disinfection,  and  the 
like.  Yet  it  should  not  be  overlooked  that  after  recovery  from  a 
well-marked  attack  patients  not  infrequently  leave  their  homes  and 
associate  with  the  public  before  their  throats  are  free  from  the  bacilli. 
Experience  shows  that  these  organisms  sometimes  remain  in  the  nose  and 
throat  in  a  virulent  form  for  five  or  six  weeks,  and  at  times  much  longer, 
after  the  clinical  symptoms  have  disappeared.  Then  again,  it  is  not 
impossible  for  the  disease  to  be  spread  by  well  persons  in  whose  throats 
the  bacilli  are  present.  It  has  been  estimated,  by  an  able  observer,  that 
these  organisms  may  be  found  in  the  throats  of  about  2  per  cent,  of  all 
well  persons. 

Milk  has  been  charged  with  spreading  diphtheria.  In  order  that  it 
should  play  this  role  the  infection  must  be  introduced  through  outside 
contamination.  Once  introduced,  bacilli  will  find  in  milk  a  good 
culture  medium  in  which  to  grow  and  multiply.  In  the  reports  of  the 
majority  of  epidemics  which  were  believed  to  have  been  caused  by  the 
milk  supply,  it  is  stated  that  either  diphtheria  prevailed  at  the  dairies 
or  the  milk  cans  were  washed  with  contaminated  water.  In  some 
instances  it  is  said  the  cows  showed  on  their  teats  and  udders  inflam- 
matory conditions. 

After  carefully  studying  a  number  of  reports  on  epidemics  alleged 
to  have  originated  from  infected  milk,  we  feel  obliged  to  say  that  the 
contention  is  supported  only  by  very  strong  presumption  that  the  milk 
was  at  fault.  There  is  no  evidence  that  amounts  to  absolute  proof. 
So  far  as  we  know  the  Klebs-Loeffler  bacilli  have  never  been  found  in 
any  of  the  suspected  milk.  A  few  years  ago  the  Board  of  Health  of 
Philadelphia  collected  samples  of  milk  from  sixty-two  houses  in  which 
diphtheria  prevailed  and  subjected  them  to  careful  bacteriological 
examination,  but  the  result  in  every  instance  was  negative.  In  this 
connection  it  might  be  well  to  add,  on  the  authority  of  I^ennox  Browne, 
"that  the  bacillus  when  grown  in  milk  loses  many  of  its  chief  character- 
istics, or,  perhaps,  it  would  be  more  correct  to  say  it  assumes  others 
peculiar  to  its  culture  medium.  It  probably  undergoes  degenerative 
changes  with  rapidity;  possibly  these  are  due  to  the  presence  of  lactic 
acid." 

Schools  are  commonly  regarded  as  an  important  factor  in  the  spread 
of  diphtheria.  It  is  a  matter  of  observation  in  large  cities  where  the 
disease  is  constantly  present  that  the  number  of  cases  increases  soon 
after  the  opening  of  the  schools  in  autumn,  and  that  the  number  is 
smallest  during  the  summer  vacation.  The  rules  created  and  enforced 
by  health  authorities,  excluding  from  school  all  children  suffering  from 
sore  throats,  and  all  those  from  families  in  which  diphtheria  exists, 
have  done  much  to  limit  the  spread  of  the  disease.  But  in  spite  of  this 
wise  sanitary  measure  it  not  infrequently  happens  that  children  attend 
school  while  suffering  from  mild  and  unrecognized  forms  of  diphtheria, 
or,  at  least,  in  whose  throats  virulent  bacilli  are  present.  Outbreaks  of 
the  disease  in  certain  districts  may  often  be  explained  in  this  way. 

On  the  contrary,  efforts  have  been  made  to  show  that  congregation  in 


Till':  hyrioLoav  of  hii'irriii'iniA  (;0J> 

schools  is  not  a  common  cause  of  cj)i(Jemics.  In  supjxjrt,  of  this  negative 
view  it  has  been  pointed  out  that  the  mortality  from  diphtheria  is  by 
far  the  greatest  among  children  imder  five  years,  who  have  not  yet 
arrived  at  the  school  age.  Jt  has  been  stated  also  that  there  frequently 
is  a  great  increase  of  its  prevalence  in  sf;hools  irnmefliatcly  after  a 
holiday  recess.  The  latter  statement  is  undoubtedly  true  of  boarding 
schools  and  kindred  institutions;  but  when  diphtheria  breaks  out  in 
such  a  school  it  is  aj)t  to  cause  not  only  a  local  epidemic,  but  so  great 
alarm  among  the  pupils  as  to  occasion  a  stampede,  and  thus  the  disease 
is  often  widely  disseminated.  When  the  infection  is  introdijced  into  a 
family  it  is  not  surprising  that  the  younger  children — those  who  have 
not  yet  attained  to  the  school  age — should  be  the  principal  sufferers. 
Therefore,  the  fact  that  the  greatest  mortality  is  found  to  be  among 
children  under  five  years  does  not  invalidate  the  view  that  schools 
operate  as  an  important  factor  in  spreading  diphtheria. 

While  writing  these  lines  a  late  issue  of  American  Medicine  comes  to 
hand  containing  this  paragraph:  "Diphtheria  of  a  somewhat  malignant 
type  is  reported  to  be  raging  in  Milton,  Mass.  The  disease  first  appeared 
among  the  pupils  of  one  of  the  public  schools,  and  afterward  spread  to 
such  an  extent  that  the  school  was  ordered  to  be  closed.  At  this  time 
there  were  28  cases  in  the  immediate  neighborhood." 

Like  all  infectious  diseases,  diphtheria  is  most  rapidly  disseminated 
in  countries  and  localities  where  there  is  the  freest  personal  inter- 
communication. Hence,  it  is  by  far  more  common  in  urban  than  in 
rural  communities.  After  having  illustrated  this  fact  in  diagrammatic 
form,  Newsholme  says:  "The  whole  of  Michigan,  which  has  a  large 
proportion  of  rural  population,  has  much  less  diphtheria  than  the 
neighboring  city  of  Chicago;  the  whole  of  INIassachusetts  has  less 
diphtheria  than  Boston  or  New  York;  the  whole  of  England  less  than 
London;  the  whole  of  Japan  less  than  its  great  towns;  the  whole  of 
South  Australia  less  than  Adelaide." 

Constitutional  Predisposition.— The  presence  of  catarrhal  affections 
of  the  mucous  membrane  of  the  nose  and  throat  seems  to  increase  the 
liability  to  diphtherial  infection.  Children  who  suffer  from  adenoid 
growths  in  the  pharynx,  with  chronic  inflammation  of  the  nasopharyngeal 
region,  and  from  enlargement  of  the  tonsils  are  regarded  as  being 
particularly  susceptible  to  the  infection.  When  these  conditions  exist 
together  they  usually  cause  what  is  known  as  mouth-breathing,  by 
which  act  the  air,  instead  of  being  warmed  and  filtered  by  passing 
through  the  nares,  goes  direct  to  the  fauces  cold  and  irritating,  and, 
perhaps,  laden  with  germs.  Lennox  Browne  writes:  "My  personal 
experience  leads  me  to  say  that  diphtheria  hardly  ever,  if  ever,  occurs 
in  a  child  under  seven  years  of  age  who  is  not  the  subject  of  one  or 
other  of  these  forms  of  glandular  overgrowth.  It  appears  needless  to 
enforce  their  tendency  to  abrogate  the  hygienic  function  of  the  nose  as 
the  first  avenue  of  respiration  and  to  induce  the  marked  deficiency  in 
vitality  and  resisting  power  to  contagion  which  are  to  be  found  in  all 
such  children." 

39 


610  DIPHTHERIA 

Everyone  knows  that  the  first  evidence  of  diphtheria  is  commonly 
seen  on  the  tonsils.  It  would,  therefore,  appear  that  these  glandular 
organs  were  the  most  vulnerable  part  of  the  body  for  attack  by  the 
Klebs-Loeffler  bacilli.  The  peculiar  anatomical  structure  of  the  tonsils, 
having  on  their  exposed  surface  deep  crypts  or  lacunte  into  which  the 
organisms  may  lodge  and  multiply,  affords  a  very  probable  explanation 
why  they  are  so  often  the  seat  of  the  disease  process.  When  these 
glands  are  inflamed  and  swollen  the  lacunae  become  deeper  and  the 
mucous  covering  so  delicate  that  they  have  been  not  inaptly  compared 
by  Virchow  to  open  wounds.  Hence,  it  is  easy  to  see  how  this  condition 
may  increase  susceptibility  to  diphtheria. 

Certain  other  diseases  with  anginose  manifestations  also  furnish  a 
marked  predisposition  to  diphtheria.  Of  these  we  would  mention 
particularly  scarlet  fever  and  measles.  The  frequency  with  which  the 
Klebs-Loeffler  bacilli  are  found  in  the  throats  of  scarlet-fever  patients 
is  really  astonishing;  according  to  our  experience  at  the  Municipal 
Hospital  they  are  present  in  10  per  cent,  to  33  per  cent,  of  all  cases. 
Indeed,  they  are  often  found  when  the  clinical  conditions  would  not 
suggest  the  existence  of  diphtheria.  These  two  diseases,  however,  not 
infrequently  coexist,  the  symptoms  peculiar  to  each  appearing  at  the 
same  time.  But  symptoms  of  diphtheria  may  develop  during  the  course 
of  scarlet  fever  or  during  conva'escence. 

As  might  be  expected  from  what  has  already  been  said,  the  catarrhal 
affection  of  the  fauces  and  upper  air  passage  incident  to  measles  renders 
the  individual  very  responsive  to  the  action  of  the  diphtheria  bacillus. 
Membranous  croup  associated  with  measles  is  by  no  means  an  infre- 
quent occurrence,  and,  moreover,  is  exceedingly  fatal.  When  measles 
prevails  in  Philadelphia  we  have  numerous  applications  for  the  admis- 
sion to  the  Municipal  Hospital  of  cases  complicated  with  membranous 
laryngitis.  Many  of  them  belong  to  the  true  type  of  diphtheria,  but 
others,  it  must  be  admitted,  are  probably  caused  by  other  bacteria,  as- 
the  diphtheria  organism  is  not  always  found. 

The  predisposition  to  diphtheria  varies  greatly  in  different  persons, 
and  often  quite  independently  of  any  known  abnormal  condition  of  the 
throat.  Children  are  much  more  susceptible  than  adults.  The  pre- 
disposition is  undoubtedly  much  more  strongly  marked  in  some  families 
than  in  others.  This  may  be  explained  on  the  supposition  that  in  the 
more  susceptible  families  there  is  an  inherited  tendency  to  the  develop- 
ment of  some  form  of  chronic  catarrh  of  the  mucous  membrane  of  the 
throat,  thus  favoring  the  operations  of  the  bacilli.  Some  writers  believe 
that  infection  through  a  healthy  mucous  membrane,  if  not  impossible, 
is  very  unlikely. 

Recurrent  Attacks. — In  most  infectious  diseases  one  attack  usually 
confers  immunity  against  subsequent  attacks.  This  is  particularly  true 
of  measles,  scarlet  fever,  and  smallpox.  But  with  regard  to  diphtheria 
this  announcement  cannot  be  made  with  equal  stress,  as  recurrent  attacks 
are  by  no  means  rare.  We  have  frequently  seen  patients  suffer  from 
a  second  attack  before  leaving  the  hospital.    Also  children  have  been 


77//';  I'JTfOLOaV  OF  DII'IITIIFUIA  ()]] 

admitted  to  the  hospital  a  second  time,  and,  in  two  or  thn^e  instances, 
a  third  time  sufl'ering  from  diphthc^ria,  after  intervals  of  a  few  weeks 
to  three  or  four  years. 

Age. — The  (h'])htli(M-ial  infection  finds  in  childrfui  the  most  favorahlf 
soil  for  its  reception  and  propagjition.  Th(;  disease  is  exceedingly 
common  amonj^  children  up  to  the  age  of  ten  years,  but  those  from 
one  to  five  years  are  most  susceptible.  Some  writers  state  that  diph- 
theria attacks  but  seldom  infants  under  a  year  old,  and  that  in  the 
first  half-year  of  life  there  is  complete  immunity  to  the  disease.  It  has 
fallen  to  our  lot  to  see  a  large  number  of  infants  suffer  and  perish  from 
this  scourge,  and  many  of  them  were  under  the  age  of  six  months. 
We  believe,  however,  the  infection  is  not  so  readily  received  at  this 
early  age.  Adults  not  infrecpiently  acquire  the  disease;  but  their  chance 
of  escaping  it  or  of  recovering  when  attacked  is  much  greater  than  is 
the  case  with  children. 

It  is  a  recognized  fact  that  in  all  epidemics  of  diphtheria  as  well  as 
in  endemics  children  are  the  first  to  suffer  from  the  disease.  They  also 
furnish  the  principal  part  of  the  mortality.  This  will  be  considered 
more  fully  under  the  head  of  prognosis.  It  is  worthy  of  notice  that  the 
laryngeal  form  of  diphtheria  is  limited  almost  entirely  to  children. 

The  following  table  shows  the  diphtheria  patients  admitted  to  the 
Municipal  Hospital  of  Philadelphia  during  the  last  decade  classified 
into  age  groups: 

Under  25  years  and 

Year.  1  year.  1-5  yrs.        5-10  yrs.      10-15  yrs.    15-25  yrs.      upward.  Total. 


1893 
1894 
1895 
1896 
1897 
1898 
1899 
1900 
1901 
1902 


217 

16  218  120  31  52  28  465 

26  327  187  46  56  65  706 

33  404  276  71  49  36  869 

34  560  437  126  89  49  1295 
42  652  447  93  47  48  1229 
38  659  462  102  62  50  1373 
40  595  473  117  90  52  1367 
30  374  287  106  56  36  889 
38  305  159  40  33  26  601 


Total  299       4076       2901       750       570       418       9011 

This  table  bears  out  the  statement  that  children  from  one  to  five 
years  of  age  are  most  susceptible  to  diphtheria;  and  also  shows  that 
the  susceptibility  diminishes  very  considerably  after  the  age  of  ten 
years.  We  would  direct  attention  to  the  table  as  showing  the  large 
number  of  infants  that  have  come  under  our  care.  As  parents  are 
naturally  loath  to  send  children  of  this  tender  age  to  a  hospital  it  is 
not  improbable  that  the  table  shows  a  smaller  proportion  of  patients 
under  the  age  of  one  year  than  if  the  entire  number  in  the  city  were 
considered. 

Sex. — It  scarcely  seems  probable  that  sex  should  exert  any  influence 
over  susceptibility  to  diphtheria.  It  has  been  stated,  however,  by  some 
observers  that  up  to  the  age  of  four  years  there  is  no  difference  in  suscept- 
ibility, but  subsequent  to  this  age  males  suffer  more  frequently  than 
females. 


612  DIPHTHERIA 

The  last  census  report  of  the  United  States  shows  that  for  the 
census  year  the  deaths  were  quite  equally  distributed  between  the 
two  sexes — 14,878  were  males  and  14,081  were  females.  This  very 
extensive  statistical  evidence  warrants  the  conclusion  that  predisposition 
to  the  disease  is  not  influenced  by  sex,  and  that  where  any  disparity  is 
found  it  is  accidental  rather  than  otherwise. 

The  following  table  shows  the  number  of  patients  admitted  to  the 
Municipal  Hospital  each  year  during  the  last  decade  divided  as  to  sex: 

Year.  Males.  Females.  Total. 

1893 .94  123  217 

1894 214  251  465 

1895 315  391  706 

1896  ...........  424  445  869 

1897 636  659  1295 

1898 562  667  1229 

1899 641  732  1373 

1900 669  698  1367 

1901 416  473  889 

1902 285  316  601 

Total 4256        4764         9011 

It  is  worthy  of  remark  that  of  the  diphtheria  admissions  to  the 
Municipal  Hospital,  Philadelphia,  the  females  have  exceeded  the  males. 
The  table  shows  that  this  was  the  case  every  year  during  the  last 
decade. 

Race. — It  cannot  be  said  that  race  plays  any  prominent  part  among 
the  predisponent  causes  of  diphtheria.  The  opinion  expressed  by  some 
observers  that  the  Jews  are  especially  liable  to  the  disease  cannot  be 
accepted  in  the  absence  of  positive  proof.  It  is  true  in  some  of  the 
large  cities  of  this  country  the  Russian  Jews  furnish  a  large  contingent 
of  the  cases  admitted  to  hospitals  for  infectious  diseases,  but  this  may 
be  explained  by  the  unsanitary  environments  of  these  people.  The 
colored  race  has  been  thought  to  possess  a  considerable  degree  of 
immunity,  but  we  have  found  no  material  difference  between  the  death 
rates  of  the  white  and  colored  patients. 

THE  BACTERIOLOGY  OF  DIPHTHERIA. 

In  1883  Klebs  first  observed  and  reported  the  constant  presence  of 
a  bacillus  in  the  false  membranes  in  diphtheria  patients. 

The  following  year  Loeffler^  isolated  these  organisms  in  pure  culture 
and  demonstrated  their  pathogenic  power  by  reproducing  the  disease 
by  inoculation  of  the  mucous  membranes  of  animals. 

Roux  and  Yersin^  studied  the  effects  of  the  diphtheria  toxin  elaborated 
by  the  bacilli,  an  investigation  which  led  up  to  the  development  of 
serotherapy. 

By  1891  the  requisite  postulates  of  Koch  concerning  the  specificity 
of  the  germ  had  been  fulfilled  as  regards  the  diphtheria  bacillus.     Its 

1  Mittheil.  aus  dem  Kaiser.  Gesundheitsamte,  1884,  Bd.  xi. 
'•i  Ann.  de  I'Institut  Pasteur,  1888-1889. 


PLATE  LVII. 


K.O 


b.  Colonic 


^  iif  i)^eu(ii)ili|)hll)oria  b.ifilli.     X   KiO.         ^•.  ('(ilinii-x  oi  diphi  Ikm  ia  i);ii-illi. 


240. 


;.  Di|.hilieriabi.-i!i;.    ^<  1000. 


r.. 


;'.  PseiKlodiphiherialjacilli.        KKK).      r/.  SiiciiK, 


1000. 


/i.  Streptococci. 

)iplitheria  Bacilli  and  Streptococ 


TlIK  liACTI'UaOLOdV  OF  Dl I'llTII I'llilA  (;].'} 

constant  presence,  its  isolation  in  pure  culture,  the  nrproductifni  of  flic 
disease  in  animals  by  inoculations  of  pure  cultures,  the  presence  of  tlic 
bacilli  in  the  orif,niial  and  in  the  experimentally  induced  disease,  dernfjii- 
strated  the  bacillus  of  Klebs  and  r.oefllcr  to  b(;  the  cause  f)f  dij)li- 
theria. 

Morphology. — The  diphtheria  bacillus  is  a  straight  or  slightly  curved, 
rod-shaped  organism  with  rounded  ends;  the  diameter  is  ordinarily 
from  0.5  to  0.8  microns  and  the  length  from  2  to  3  or  more  microns. 

It  is  subject  to  the  greatest  variation  of  form;  this  is  true  to  suc-h  an 
extent  that  polymorphism  is  an  important  characteristic;. 

Abbott^  says  that  spindle  and  club  shapes  are  extremely  common, 
and  that  not  rarely  many  of  the  rods  stain  irregularly;  in  some  of  them 
very  deeply  stained  round  or  oval  points  can  be  detected.  He  adds: 
"When  cultures  are  examined  microscopically  it  is  especially  char- 
acteristic to  find  irregular,  bizarre  forms,  such  as  rods  with  one  or  both 
ends  swollen,  and  very  frequently  roc^s  broken  at  irregular  intervals 
into  short,  sharply  defined  segments,  either  round,  oval,  or  with  straight 
sides."  The  form  and  size  of  the  bacillus  vary  gready  according  to 
the  culture  medium  used;  it  is  smallest  and  most  regular  on  glycerin 
agar;  on  Loeffler's  blood  serum  one  sees,  "instead  of  the  very  short 
spindle,  lancet,  club-shaped,  always  segmented  and  regular  staining 
forms  as  seen  upon  glycerin  agar,  long  sometimes,  extremely  slender, 
sometimes  thicker,  irregular-staining  threads  that  are  usually  clubbed 
and  frequently  pointed  at  their  extremities." 

In  1900  Wesbrook  read  before  the  Association  of  American  Physicians 
a  carefully  prepared  article  on  the  various  morphological  types  of  diph- 
theria bacilli.  He  divided  them  into  three  groups — the  granular  (those 
with  deeply  staining  granules),  the  barred  (those  with  transverse  bands), 
and  the  soHd  or  evenly  staining  forms.  Further  subdivisions  of  these 
groups  were  discussed. 

The  granular  type  of  bacillus  is  the  one  most  commonly  seen  in  the 
beginning  of  the  disease;  later  these  give  way  wholly  or  in  part  to  the 
barred  or  solid  forms;  soHd  types  may  sometimes  be  replaced  by  the 
granular  when  convalescence  is  established  and  just  before  the  throat 
begins  to  clear.  Wesbrook's  findings  have  been  more  recently  con- 
firmed by  Gorham. 

The  relation  of  the  sohd  forms  to  true  diphtheria  bacilli  is  still 
unsettled.  They  are  said  to  be  sometimes  encountered  as  variants  in 
pure  cultures  of  diphtheria  organisms.  Certain  of  the  sohd  forms  have 
characteristic  i  which  seem  to  distinguish  them  from  the  diphtheria 
bacillus  and  to  class  them  with  the  pseudodiphtheria  organisms.  For 
instance,  some  of  the  solid  forms  fail  to  produce  acid  in  dextrose  bouillon, 
a  property  which  is  possessed  by  the  true  diphtheria  bacilli." 

Staining  Properties. — ^llie  diphtheria  bacillus  stains  well  with  the 
ordinary  aniline  dyes  and  with  the  Gram  stain.     The  best  results  are, 

1  Principles  of  Bacteriology,  fifth  edition. 

2  Statements  made  in  a  report  on  "  Diphtheria  Bacilli  in  Well  Persons"  by  a  Committee  of  the 
Massachusetts  Association  of  Boards  of  Health,  Boston,  1902. 


614  DIPHTHERIA 

however,  obtained  with  Loeffler's  alkahne  solution  of  methylene  blue, 
which  brings  out  the  granules  well.    This  solution  is  made  up  of 

Concentrated  alcoholic  solution  of  methylene  blue      ....      30  c.c. 
Caustic  potash  in  1  :  10,000  solution 100    " 

Neisser  Staiii. — The  stain  suggested  by  Neisser  in  1897  is  said  by 
Abbott  to  enable  one  to  overcome  in  a  very  large  part  the  difficulty 
occasionally  experienced  in  differentiating  the  diphtheria  bacillus  from 
other  throat  organisms  which  may  simulate  it.  The  method  is  described 
by  Abbott  as  follows :  The  culture  to  be  tested  should  be  grown  upon 
Loeffler's  blood-serum  mixture  solidified  at  100°  C. ;  it  should  develop 
at  a  temperature  not  lower  than  34°  C.  and  not  higher  than  36°  C, 
and  it  should  be  not  younger  than  nine  and  not  older  than  twenty-four 
hours.  A  cover-glass  preparation  made  from  such  culture  is  stained 
for  from  one  to  three  seconds  in  the  following  solution: 

Methylene  blue  (Grubler's) 1  gram. 

Alcohol  (96  per  cent.) 20  c.c. 

When  dissolved,  mix  with 

Acetic  acid 50  c.c. 

Distilled  water 950    " 

After  thoroughly  rinsing  in  water  the  preparation  is  then  stained 
for  from  three  to  five  seconds  in  vesuvin  (Bismarck  brown),  2  grams 
dissolved  in  a  litre  of  boiling  distilled  water,  filtered  and  allowed  to  cool. 
It  is  again  rinsed  in  water  and  examined  as  a  water-mount  or  dried 
and  mounted  in  balsam. 

When  so  treated  the  bacilli  appear  as  faintly  stained  brown  rods  in 
which  from  one  to  three  brown  granules  are  always  to  be  observed. 
The  dark  granules  are  at  one  or  both  poles  of  the  cell,  are  more  or  less 
oval,  and  usually  seem  to  bulge  a  little  beyond  the  contour  of  the  bacillus 
in  which  they  are  located.  In  the  vast  majority  of  cases  it  seems  safe 
to  regard  all  bacilli  that  do  not  stain  in  this  manner  as  distinct  from 
bacillus  diphtherise  (Abbott).  ^ 

Biological  Characters. — The  diphtheria  bacillus  is  aerobic,  non- 
motile  and  liquefying,  and  does  not  form  spores.  It  grows  freely  in 
the  presence  of  oxygen,  but  is  also  a  facultative  anaerobic  (Sternberg). 

The  diphtheria  bacillus  is  destroyed  by  exposure  to  a  temperature  of 
58°  C.  (136°  F.)  for  ten  minutes.  In  the  dried  state  it  may  maintain' its 
vitality  for  a  long  period.  Park  found  active  bacilli  on  dried  membrane 
after  seventeen  weeks,  and  Roux  and  Yersin  living  but  non-virulent 
bacilli  after  five  months.  Bacilli  were  found  by  Abel  to  persist  for 
five  months  on  children's  toys  kept  in  the  dark.  When  the  organisms 
are  preserved  in  sealed  tubes  and  protected  from  light  and  heat  they 
may  remain  virulent  for  years. 

Growth  on  Loeffler's  Blood  Serum.^ — This  is  the  best  medium  for  the 
growth  of  the  diphtheria  organism  and  the  one  which  is  ordinarily 
employed  for  the  culture  test.  It  is  a  mixture  of  three  parts  of  blood 
serum  with  one  part  of  bouillon,  containing  1  per  cent,  of  peptone, 


Till':  liACTF/illOLOCY  OF  hi I'II'I'IIIuH A  015 

1   per  cent,  of  grape-sugar,  aixl  0.5  \n's  cent,  of  .sodluni  diloiiilf,-;  the 
mixture  is  sterilized  and   solidified   at  a  low  tcniper.'itiire  (Stfrnlx-rgj. 

I'he  di[)litheria  organism  grows  so  mucli  more  {>njmptly  upon  tliis 
mixture  than  other  mouth  and  throat  bacteria  that  at  the  end  fjf  twenty- 
four  liours  the  (H[)htheria  colonies  may  be  readily  recogniyx-d  while  the 
other  colonies  are  still  inconspicuous. 

Growth  on  Glycerin  Agar. — The  development  u[)on  this  medium 
is  nuich  more  delicate  and  less  luxuriant  than  U|>f)n  bUjrjd  serum. 
The  colonies  apj)ear  at  first  on  the  surface  as  Hat,  almost  transparent, 
dry,  non-glistening,  non-elevated  round  points.  When  slightly  inagnified 
they  are  seen  to  be  granular  with  an  irregular  central  marking.  The 
colonies  are  always  dry  in  appearance;  the  deep  colonies  are  coarsely 
granular  (Abbott).  Bacilli  taken  directly  from  the  throat  develop 
poorly,  or  not  at  all,  on  agar,  but  subcultures  may  grow  very  well. 

Growth  on  Gelatin. — The  colonies  on  gelatin  do  not  present  tlieir 
characteristic  appearance  in  less  than  three  days.  If  slightly  magnified 
the  colonies  show  a  denser  centre  than  periphery;  the  border  is  notched. 
The  colonies  are  granular,  particularly  the  deep  ones  (Abbott). 

Growth  on  Bouillon. — According  to  Abbott,  the  growth  on  bouillon 
produces  fine  clumps  which  fall  to  the  bottom  of  the  tube  or  become 
deposited  on  its  sides  without  causing  diffuse  clouding.  Sometimes 
the  clumps  cannot  be  discerned  by  the  naked  eye.  The  reaction  of 
the  bouillon  is  at  first  acid  and  later  alkaline.  According  to  Schabad 
the  maximum  acidity  occurs  most  often  on  the  second  day,  although 
sometimes  it  may  be  on  the  third  and  rarely  on  the  fourth  or  later. 

Many  observers  regard  the  acid  formation  a  feature  of  importance 
in  distinguishing  between  the  diphtheria  and  pseudodiphtheria  organism ; 
the  value  of  this  test,  however,  is  not  yet  definitely  determined. 

Growth  in  Milk. — Sternberg  states  that  milk  is  a  favorable  medium 
for  the  growth  of  the  diphtheria  bacillus  and  adds  that,  as  it  grows  at 
a  comparatively  low  temperature  (20°  C),  this  fluid  may  become  a 
medium  for  conveying  the  bacillus  from  an  infected  source  to  throats 
of  previously  healthy  children.  The  appearance  of  the  milk  remains 
if  j.  unchanged. 

^''  Growth  on  Potato. — Welch  and  Abbott  state  that  the  diphtheria 
bacillus  grows  on  ordinary  steamed  potato  without  any  preliminary 
treatment,  but  that  the  growth  is  usually  entirely  invisible  or  is  indicated 
by  a  dry,  thin,  glaze  after  several  days.  At  the  end  of  twenty-four 
hours,  at  a  temperature  of  35°  C,  microscopic  scrapings  of  the  potato 
reveal  a  decided  increase  of  the  bacilli. 

Pathogenesis. — According  to  Park  the  diphtheria  bacillus  is  patho- 
genic for  guinea-pigs,  rabbits,  chickens,  pigeons,  small  birds,  and  cats; 
to  a  less  extent  it  is  pathogenic  for  horses,  cattle,  dogs,  and  goats,  but 
not  for  rats  and  mice.  The  rat  and  the  mouse  exhibit  a  remarkable 
insusceptibility;  a  dose  of  2  c.c.  of  a  bouillon  culture  will  kill  a  rabbit, 
but  not  a  mouse. 

The  inoculation  of  such  animals  as  cats  and  rabbits  by  rubbing  a 
pure  culture  of  the  diphtheria  bacillus  upon  the  mucous  surface  of  the 


QIQ  DIPHTHERIA 

opened  trachea  produces  a  disease  which  is  essentially  the  same  as 
that  seen  in  man.  The  animal  usually  dies  in  from  two  to  four  days, 
not  from  a  general  invasion  by  the  diphtheria  organism,  but  as  a  result 
of  the  absorption  of  the  soluble  toxins  formed  at  the  seat  of  infection. 

The  wound  at  autopsy  is  covered  with  a  grayish,  adherent,  necrotic, 
distinctly  diphtheritic  layer.  The  surrounding  subcutaneous  tissues  are 
oedematous  and  the  lymphatic  glands  at  the  angles  of  the  jaw  are 
swollen  and  reddened.  The  mucous  membrane  of  the  trachea  at  the 
site  of  inoculation  is  covered  with  a  firm,  grayish-white,  loosely  attached 
pseudomembrane  identical  in  all  respects  with  that  seen  in  human 
diphtheria.  The  membrane  and  the  oedematous  fluid  about  the  wound 
show  the  presence  both  by  smears  and  by  culture  of  the  diphtheria 
bacillus  (Abbott). 

In  animals  that  did  not  die  too  quickly  Roux  and  Yersin  have  noted 
the  development  of  paralysis  of  the  posterior  extremities. 

It  is  a  well-established  fact  that  the  diphtheria  bacillus  under  ordinary 
circumstances  remains  in  the  vicinity  of  the  site  of  inoculation.  When 
it  is  found  in  the  blood  or  visceral  organs  its  presence  is  probably 
accidental.  The  widespread  changes  in  important  organs  in  diphtheria 
must  therefore  be  ascribed  to  a  diffusible  circulating  poison  produced 
by  the  diphtheria  organism  in  its  original  nidus.  That  such  is  the  case 
was  proved  by  Roux  and  Yersin  in  1888,  when  they  demonstrated  the 
presence  of  a  poison  in  diphtheria  cultures  which  were  filtered  through 
porous  porcelain.  It  was  found  that  old  cultures  and  particularly  those 
of  alkaline  reaction,  had  a  much  greater  toxic  potency  than  recent 
cultures  of  acid  reaction.  Injection  of  filtered  cultures  into  susceptible 
animals  produced  local  redema,  congestion  and  hemorrhage  of  the 
internal  organs,  effusion  into  the  pleural  cavity,  etc.  It  is  thus  seen 
that  practically  all  of  the  symptoms  produced  by  the  injection  of  pure 
cultures  of  bacilli  may  be  obtained  by  injection  of  the  filtered  cultures 
save  the  production  of  a  false  membrane.  Sternberg  remarks  that  this 
deadly  toxin  appears  to  be  an  albuminoid  substance  (a  toxalbumin),  but 
its  exact  chemical  composition  has  not  yet  been  determined. 

Virulence  and  Avirulence  of  Diphtheria  Bacilli.^"V\hen  virulent 
bacilli  are  grown  in  bouillon,  soluble  toxins  are  developed  which  produce 
certain  noxious  effects  upon  guinea-pigs.  Even  where  the  l>acilli  are 
removed  by  filtration  the  injection  produces  death  of  the  animal. 
Practically  all  bacilli  derived  from  clinical  cases  of  diphtheria  produce 
toxins  with  these  properties.  Conversely,  it  would  seem  that  bacilli 
that  produce  no  toxins  in  bouillon  will  not  produce  them  in  the  human 
subject.  Wesbrook  and  Gorham  rather  dissent  from  the  view  generally 
accepted,  and  believe  that  animal  inoculation  of  cultures  is  no  definite 
test  of  virulence  of  the  bacilli  in  the  human  species. 

Formerly  the  non-virulent  bacilli  were  classed  by  some  writers  in 
a  group  apart  from  the  genuine  diphtheria  organism.  It  is  now  pretty 
generally  recognized  that  true  diphtheria  bacilli  may  possess  varying 
grades  of  virulence.  Those  occurring  in  the  throats  of  convalescent 
patients  and  those  found  in  the  throats  of  healthy  persons  have  fre- 


77//';  liACTI'lh-IOIJXlY  01''  Dl I'll'I'll Klil A  (;  |  7 

quently  a  very  low  i^ritdc  of  vii-iilcncc.  'I'lic  less  vinilcni,  lorins  rominonly 
increase  in  niiinhcrs  ;is  |)r()^n-css  lovvunl  the  rcfovery  of  (li[)litijeria 
advances. 

The  Distribution  of  Diphtheria  Bacilli  in  the  Body. — Abbott  says: 
"In  a  certiiiii  luniihcr  of  cases  (li[)litli<Tiji  hacilli  liuvc  Ijcen  found  in 
the  l)loo(l  and  internal  orfraiis  of  individuals  dead  of  the  disease;  but 
all  that  has  been  learned  from  study  of  the  secondary  manifestations 
of  di})hthcria  tends  to  the  opinion  that  tliey  are  in  no  way  dependent 
upon  the  immediate  presence  of  bacteria  and  that  the  occasional  appear- 
ance of  diphtheria  bacilli  in  the  internal  organs  is  in  all  probaljility 
accidental,  and  usually  unimportant." 

General  infection  with  the  diphtheria  l)aeillus  has  been  reported 
by  a  considerable  number  of  writers. 

Frosch'^  was  the  first  to  note  the  presence  of  diphtheria  bacilli  in 
the  internal  organs  of  patients  dead  of  diphtheria;  he  found  them  in 
the  heart's  blood,  liver,  spleen,  kidney,  and  lymph  nodes  in  ]0  out  of 
15  cases  examined. 

Kutscher  found  the  bacilli  in  8  out  of  9  cases  in  the  lung.  Kanthack 
and  Stevens  found  them  in  the  spleen  in  10  out  of  21  cases,  in  the 
kidney  in  2  out  of  3  cases,  and  in  the  lungs  in  each  of  26  cases. 

Wright  and  Stokes,  in  a  report  of  31  eases,  found  the  diphtheria 
organism  30  times  in  the  lungs,  9  times  in  the  liver,  7  times  in  the 
mesenteric  lymph  nodes,  5  times  each  in  the  spleen  and  heart's  blood, 
4  times  in  the  cervical  lymph  nodes,  and  twice  each  in  the  brain  and 
bronchial  glands. 

Genersisch  examined  25  cases  of  septic  diphtheria  in  some  of  which 
he  failed  to  find  the  streptococcus  in  the  blood  or  internal  organs;  he 
concluded  that  the  diphtheria  bacillus  was  capable  alone  of  producing 
septic  symptoms.  Stephens  and  Parfitt  have  reported  a  case  of  general 
infection  with  the  diphtheria  bacillus  in  which  these  organisms  were 
recovered  from  the  blood  during  life.  In  a  child  with  an  unusually 
high  and  unexplained  temperature,  suffering  from  diphtheria  at  the 
Municipal  Hospital,  we  recovered  the  diphtheria  bacillus  in  pure 
culture  from  the  blood  a  day  before  death. 

Councilman,  Mallory,  and  Pearce  have  extensively  cultured  the 
various  organs  in  161  diphtheria  autopsies.  They  found  bacilli  in  the 
heart's  blood  in  pure  culture  7  times,  and  4  other  times  in  association 
with  other  organisms.  Diphtheria  bacilli  were  found  in  the  liver  30 
times,  in  the  spleen  19  times,  and  in  the  kidneys  27  times.  These  inves- 
tigators remark,  apropos  of  these  findings:  "^Yhether  the  diphtheria 
bacillus  does  or  does  not  continue  to  produce  the  toxic  products  where- 
ever  it  may  be  in  the  blood  or  internal  organs  it  is  impossible  to  say, 
but  from  the  number  of  fatal  cases  with  such  an  infection  it  would  seem 
very  probable  that  it  does.  Kanthack  and  Stephens,  and  Genersisch 
also,  incline  to  this  opinion. 

Diphtheria  bacilli  have  been  thrice  found  upon  the  vegetations  of  an 
acute  ulcerative  endocarditis.     These  have  been  reported  by  Howard, 

1  Zeitschr.  f.  Hygiene  und  Infectionskr.,  1S93,  Bd.  xiii.  pp.  49-52. 


618  DIPHTHERIA 

Wright,  and  Councilman,  Mallory,  and  Pearce.  The  antrum  and 
accessory  nasal  sini  ses  may  harbor  diphtheria  bacilli  for  a  long  time. 
Wolff,  in  autopsies  on  15  severe  cases  of  diphtheria,  found  diphtheria 
bacilli  in  the  antra  in  12.  Councilman,  Mallory,  and  Pearce  examined 
the  antra  in  52  Cases;  in  16  of  these  diphtheria  bacilli  were  recovered 
from  both  sides.  They  suggest  that  infection  of  the  antra  may  explain 
the  persistence  of  the  bacilli  in  the  nasal  discharge  for  protracted  periods. 

The  middle  ears  were  examined  in  144  cases.  In  86  they  were  found 
diseased,  and  in  37  diphtheria  bacilli  were  recovered  from  one  or  both 
ears.    They  were  usually  found  in  association  with  other  bacteria. 

Persistence  of  Diphtheria  Bacilli  in  the  Throat. — Virulent  bacilli 
may  persist  for  varying  periods  in  the  throats  of  persons  who  have 
recovered  from  diphtheria.  In  the  vast  majority  of  cases  they  dis- 
appear ifi  from  one  to  two  weeks  after  the  disappearance  of  the  mem- 
branous exudate.  Park  and  Beebe,  in  a  study  of  605  consecutive  cases, 
found  the  bacilli  absent  within  three  days  after  the  disappearance  of 
the  membrane  in  304;  in  176  cases  they  persisted  for  seven  days;  in 
12,  for  three  weeks;  in  4,  for  four  weeks,  and  in  2,  for  nine  weeks. 
Later,  Park  saw  a  case  in  which  the  bacilli  were  found  for  six  months. 
Abbott  has  observed  a  case  in  which  the  cultures  examined  remained 
positive  for  128  days.  In  the  Boston  City  Hospital,  where  three  negative 
cultures  are  required  before  the  patient  is  discharged,  cases  have  been 
detained  for  six,  seven,  eight,  and  nine  weeks,  and  even  three  months, 
on  account  of  the  persistence  of  bacilli  in  the  nose.  I^e  Gendre  and 
Pochon  described  in  1895  a  case  in  which  the  bacilli  persisted  in  the 
nose  for  fifteen  months  after  an  attack  of  nasal  diphtheria. 

Diphtheria  Bacilli  in  the  Throats  of  Healthy  Persons.^ — There  are 
two  factors  necessary  for  the  production  of  diphtheria — the  presence 
of  the  specific  bacillus  and  the  existence  in  the  host  of  susceptibility  to 
the  disease.  Many  persons  appear  to  be  able  to  harbor  virulent  diph- 
theria bacilli  in  their  throats  without  contracting  the  disease.  In  1894 
Park  and  Beebe  examined  the  throats  of  330  healthy  persons  who  had 
not,  as  far  as  was  known,  come  in  contact  with  persons  suffering  from 
diphtheria.  Of  this  number  virulent  bacilli  were  found  in  8,  2  of  whom 
later  developed  the  disease.  In  24  of  the  330  healthy  throats  non- 
virulent  or  attenuated  forms  of  the  diphtheria  organisms  were  found. 

This  question  has  been  recently  studied  with  care  by  a  Committee 
of  the  Massachusetts  Association  of  Boards  of  Health,  composed  of 
men  of  high  scientific  standing.^    We  quote  freely  from  the  report: 

"All  observers  are  not  in  accord  as  to  the  morphological  appearances 
which  are  to  be  considered  as  characteristic  of  the  diphtheria  organism. 
That  there  is  considerable  divergence  of  opinion  among  bacteriologists 
as  to  what  should  be  classed  as  genuine  diphtheria  bacilli. is  evidenced 
by  the  great  discrepancy  in  the  prevalence  of  diphtheria  organisms  in 
the  throats  of  well  persons  as  reported  by  different  investigators.  In 
Boston  about  1  per  cent,  were  considered  positive;  in  Brookline  (Mass.), 

1  Report  on  Diphtheria  Bacilli  in  Well  Persons,  Journal  of  the  Massachusetts  Association  of  Boards 
of  Health,  July,  1902. 


THE  liACTEIUOl/XlY  O/''  Dl I'llTII EIUA  019 

2.3  [)('!•  cent.;  in  Lowell,  1.2  per  eeiil. ;  in  Springfield,  I  .<!  per  cent.;  in 
Providence,  \)  per  cent.,  and  in  the  District  of  (lolurnhia,  22  p(T  cent." 

The  conunittee  states  that  it  feels  justified  in  the  inference  that  in 
urban  coinnnniitics  at  least  1  to  2  per  cent,  of  ;ill  well  per.sons  ainon^ 
the  general  public  are  infected  with  genuine  diphtheria  bacilli,  and 
exposed  persons  in  families  and  schools  in  from  8  to  50  per  cent,  of 
the  cases. 

There  are  two  classes  of  [x-rsons  carrying  diphtheria  i)aeilli  in  their 
throats — those  exposed  to  the  disease  and  those  in  whom  no  ex})osnre 
is  known.  Among  the  general  unexposed  [)ublic  about  3  per  cent,  of 
the  people  have  ty])ical  dij>htheria  bacilli  in  their  throats.  In  the 
eastern  part  of  the  United  States  it  is  1.3!)  per  cent. 

"This  would  mean  in  Boston,  if  the  smaller  figure  be  u.sed,  abont 
<S000  such  cases."  The  committee  concludes  that  "it  is  im])racticable  to 
isolate  v^^ell  persons  infected  with  diphtheria  bacilli  if  such  persons 
have  not,  so  far  as  known,  been  recently  exposed  to  the  disease."  The 
committee  likewise  believes  that  "it  is  not  advisa])le  as  a  matter  of 
routine  to  isolate  from  the  public  all  the  well  persons  in  infected  families, 
schools,  and  institutions."  It  does,  however,  counsel  that  children 
in  infected  families  should  be  kept  away  from  school  and  public  places, 
and  that  milkmen  should  not  be  allowed  to  continue  their  business. 

In  considering  the  virulence  of  the  bacilli  found  in  healthy  throats, 
it  is  shown  that  only  about  17  per  cent,  of  the  1  to  2  per  cent,  of  persons 
harboring  diphtheria  bacilli  have  virulent  bacilli  which  are  dangerous 
to  the  public  health. 

Diphtheria  Bacilli  in  Persons  Exposed  to  ihe  Disease. — Park  found  50 
per  cent,  of  the  children  exposed  to  diphtheria  in  New  York  tenement 
houses  to  have  Klebs-Loeffler  bacilli  in  their  throats.  Chapin,  in 
Providence,  found  bacilli  in  16  per  cent.,  and  Kober,  in  Breslau,  in  S  per 
cent.  The  bacilli  in  the  throats  of  healthy  exposed  persons  are  probably 
of  the  same  virulence  as  those  in  the  diseased  individual,  and  such  per- 
sons should  therefore  be  isolated,  according  to  the  committee  above 
mentioned,  until  free  of  the  bacilli. 

Pseudodiphtheria  Bacilli. — Considerable  diversity  of  opinion  exists 
among  bacteriologists  at  the  present  time  as  to  the  proper  classification 
of  certain  bacilli  which  are  morphologically  and  tinctorially  identical 
with  the  diphtheria  organism,  but  which  differ  from  it  in  other  respects. 

There  appear  to  be  two  schools  of  opinion  upon  the  subject,  the  one 
proclaiming  the  identity  of  the  diphtheria  and  diphtheria-like  bacteria 
and  the  other  asserting  that  they  belong  to  separate  and  distinct  classes. 

Most  writers  agree  that  the  non-virulent  and  non-toxic  Loeffier  bacilli 
are  to  be  regarded  as  true  diphtheria  organisms  which  have  merely 
suffered  attenuation. 

There  are,  however,  other  organisms  which  resemble  the  diphtheria 
bacillus  very  closely,  but  dift'er  therefrom  not  only  in  the  absence  of 
toxin  production,  but  also  in  certain  other  particulars.  Among  these 
may  be  included  the  so-called  xerosis  bacillus,  wdiich  is  commonly  found 
in  the  eyes  in  the  condition  known  as  xerosis  conjunctiva?. 


e20  DIPHTHERIA 

According  to  Park,  "the  variety  of  pseudodiphtheria  bacillus  most 
commonly  seen  is  rather  short,  plump,  and  more  regular  in  size  and 
shape  than  the  Klebs-Loeffler  bacillus.  On  blood  serum  the  growth  is 
much  like  that  of  the  true  diphtheria  organism.  I'he  great  majority  of 
bacilli  in  any  culture  show  no  polar  granules  by  the  Neisser  method  and 
stain  solidly  with  Loeffler's  methylene-blue  solution.  They  do  not  pro- 
duce acid  in  glucose  bouillon.  They  are  found  in  about  1  per  cent,  of 
normal  throats  and  noses.  Neisser's  stain  is  of  value  in  these  cases,  but, 
unfortunately,  the  absence  of  the  stained  bodies  is  not  sufficient  ground 
to  exclude  the  possibility  of  their  being  true  diphtheria  bacilli." 

Schabad^  has  made  a  careful  study  of  the  various  methods  of  differ- 
entiating between  genuine  diphtheria  and  pseudodiphtheria  bacilli. 
He  concludes  as  follows: 

1.  Diphtheria  bacilli  and  pseudodiphtheria  bacilli  are  two  distinct 
organisms. 

2.  The  difference  between  them  lies  in  their  growth  in  different 
culture  media  (especially  agar  and  ascitic  fluid),  in  their  morphology, 
reaction  in  bouillon  culture,  coloration  with  Neisser's  stain,  and  patho- 
genesis for  animals. 

3.  Neisser's  stain  and  the  reaction  in  bouillon  are  the  most  important 
means  of  differential  diagnosis. 

4.  Avirulent  diphtheria  bacilli  should  be  distinguished  from  pseudo- 
diphtheria bacilli;  they  are  in  all  respects  identical  with  virulent  diph- 
theria bacilli  save  in  their  lack  of  virulence. 

5.  To  the  mistaking  of  avirulent  diphtheria  bacilli  for  pseudo- 
diphtheria bacilli  is  attributable  the  failure  of  many  writers  to  attain 
definite  results  with  Neisser's  stain  and  reaction  in  bouillon. 

6.  Avirulent  diphtheria  bacilli  can,  in  all  cases,  be  distinguished  by 
the  above  methods  from  pseudodiphtheria  bacilli. 

A  diphtheria-like  bacillus  which  produces  little  or  no  acid  in  a  bouillon 
culture,  which  does  not  show  typical  polar  granules  when  stained  by 
the  Neisser  method,  and  which  will  not  kill  guinea-pigs,  may  be  set 
down  as  a  pseudodiphtheria  organism.  Such  a  bacillus  will  not  produce 
diphtheria  in  the  human  subject,  and  its  presence  in  healthy  throats 
need  not  give  concern. 

INCUBATION  PERIOD. 

Incubation.- — The  period  of  incubation  is  the  interval  between  the 
moment  of  receiving  the  infection  and  the  beginning  of  symptoms. 
It  is  believed  that  this  period  may  vary  somewhat  according  to  the 
activity  or  virulence  of  the  infecting  organism  and  the  receptivity  of  the 
individual.  When  the  organisms  lodge  upon  a  mucous  membrane 
which  is  readily  penetrated  the  diphtherial  process  is  apt  to  appear 
sooner  than  where  this  membrane  has  greater  resistance. 

Where  the  conditions  are  favorable  the  bacilli  doubtless  begin  their 

1  Beitriigezurdiff.  diag.  des  Diph.  u.  Pseudodiph.  bacillus,  Jahrbuch  f.  Kinderheilk,  October,  1901; 
quoted  by  Northrup,  article  on  Diphtheria,  Nothnagel's  Encyclopedia  of  Practical  Medicine. 


INClIBAriON  PI'JUfr)!)  021 

work  as  soon  as  they  have  effected  a  lodgement,  l)ijt  changes  at  the  seat 
of  disease  are  not  recognized  nntil  the  j)rocess  is  sufficiently  far  advancwi 
to  show  the  characteristic  exiulate.  The  constitutional  disturbances, 
such  as  fever  and  other  subjective  symptoms,  usually  do  not  appear 
until  the  local  manifestations  have  reached  a  certain  degree  of  intensity. 
It  is  quite  possible,  therefore,  that  mild  cases  may  not  be  recognized 
as  early  as  severe  ones,  and  thus  the  period  of  incuV)ation  among  the 
former  may  sometimes  appear  to  be  longer. 

Some  observers  believe  that  this  period  is  shorter  during  the  ej)idemic 
prevalence  of  diphtheria,  especially  when  of  a  malignant  type,  than  when 
the  disease  occurs  sporadically.  In  most  cases  it  is  difficult  to  determine 
the  exact  moment  of  infection.  This  can  only  be  known  when  there 
has  been  but  a  single  exposure.  It  would  seem  that  there  should  be  no 
difficulty  in  determining  the  period  of  incubation  from  observations  in 
a  large  hospital,  and  yet  we  find  that  nurses  and  other  attendants  who 
take  diphtheria  fall  ill  at  variable  periods  after  commencing  work.  In 
the  vast  majority  of  instances,  however,  the  symptoms  of  the  disease 
appear  during  the  first  week  of  service.  Occasionally  a  nurse  will  work 
for  three  or  four  weeks  before  manifesting  any  evidence  of  infection. 
One  of  our  nurses  performed  her  duties  for  one  year  before  she  fell  ill 
with  diphtheria.  It  is  evident,  therefore,  that  the  infecting  organisms 
may  find  in  an  individual  a  more  favorable  soil  at  one  time  than  at 
another,  and  this  variation  of  susceptibility  adds  to  the  difficulty  of 
establishing  the  period  of  incubation. 

There  is  no  doubt,  however,  that  in  comparison  with  most  other 
infectious  diseases  the  period  of  incubation  of  diphtheria  is  relatively 
short.  Most  observers  fix  the  period  from  two  to  three  days;  some 
believe  that  it  may  vary  from  one  to  eight  days,  and  others  allow  that 
in  exceptional  cases  it  is  as  long  as  twelve  to  fourteen  days.  We  believe 
that  in  the  vast  majority  of  instances  it  is  from  two  to  five  days. 

Lennox  Browne  says:  ''The  experimental  incubation  period,  when 
communicated  by  inoculation  in  the  lower  animals,  is  short,  and  varies 
from  twelve  hours  to  three  days.  It  is  said  to  be  about  the  same  period 
when  a  human  patient  is  infected  by  direct  contact,  and  our  own  experi- 
ence leads  us  to  concur  that  the  disease  is  not  infrequently  developed 
at  the  minimum  interval. 

"Leslie  Phillips  reports  a  very  interesting  case  in  wliich  some  of  the 
same  instruments  were  used  on  the  same  day,  first  in  the  operat  on 
for  tracheotomy  for  diplitheria,  and,  secondly,  for  circumcision;  the 
circumcised  child  had  pseudomembrane  on  the  prepuce  on  the  fourth 
day. 

"In  ordinary  circumstances,  the  period  between  the  exposure  to  the 
contagion  and  the  appearance  of  false  membrane  in  the  throat  is  prob- 
ably from  one  to  four  days.    A  longer  interval  is  exceptional." 


622  DIPHTHERIA 

THE  SYMPTOMATOLOGY  OF  DIPHTHERIA. 

Not  infrequently  the  characteristic  symptoms  of  diphtheria  are  pre- 
ceded by  sKght  indisposition,  such  as  lassitude,  loss  of  appetite,  headache, 
nausea  and  sometimes  vomiting,  and  general  malaise.  These  prodromes, 
however,  are  not  distinctly  different  from  what  may  be  seen  in  many 
other  affections.  There  may  be  slight  stiffness  of  the  neck,  with  hyper- 
sensitive lymph  glands  near  the  angle  of  the  jaw,  and  a  little  incon- 
venience experienced  in  deglutition.  On  inspection  the  fauces  may  be 
found  hypergemic.  There  may  be  mild  chilly  sensations,  and,  in  children, 
convulsions  sometimes  occur.  The  temperature  is  apt  to  be  only 
slightly  elevated.  These  mild  symptoms  rarely  continue  longer  than  a 
few  hours  before  the  true  nature  of  the  disease  is  revealed. 

Vomiting  is  by  no  means  so  constant  a  precursory  symptom  of  diph- 
theria as  of  scarlet  fever.  The  pain  in  the  fauces  and  at  the  angle  of 
the  jaw  is  but  slight  as  compared  with  that  experienced  in  ordinary 
tonsillitis.  Indeed,  the  comparative  absence  from  pain  at  this  stage 
of  the  disease  is  of  considerable  significance  in  the  matter  of  diagnosis. 
There  may  be  diarrhoea  or  constipation;  one  is  just  as  liable  to  be  met 
with  as  the  other.  The  fauces  often  feel  dry,  and  there  is  a  disposition 
to  hawk  and  clear  the  throat. 

When  the  disease  is  going  to  assume  the  laryngeal  form,  the  voice, 
often  at  an  early  stage,  becomes  husky,  even  before  any  membrane 
has  appeared.  Along  with  this  symptom  there  is  very  commonly  a 
shrill,  brassy  cough,  and  sometimes  slight  dyspnoea,  resulting  from  a 
mild  spasmodic  affection  of  the  larynx. 

Throat. — The  first  positive  evidence  of  diphtheria  is  usually  seen  in 
the  throat.  As  stated  under  the  head  of  etiology,  the  tonsils  seem  to 
favor  the  lodgement  and  propagation  of  the  specific  bacilli;  for  in  the 
vast  majority  of  cases  it  is  on  these  glands  that  the  disease  process 
begins.  The  fauces  are  commonly  red  and  inflamed,  and  the  tonsils 
may  or  may  not  be  swollen,  although  in  most  cases  the  swelling  is 
marked.  Small  spots  of  exudate  now  appear  on  their  surface  or  in 
their  crypts — the  latter  being  a  common  seat  of  this  process.  In  mild 
cases  this  condition  does  not  increase.  It  is  then  difficult  to  distinguish 
between  diphtheria  and  tonsillitis  without  the  aid  of  bacteriological 
examination.  Patients  with  the  latter  affection  are  often  sent  to  the 
hospital  on  a  mistaken  diagnosis. 

In  the  better-marked  form  of  the  disease  the  small  patches  of  exudate 
rapidly  spread,  covering  not  infrequently  the  entire  tonsillar  surface 
in  less  than  twenty-four  hours.  This  local  manifestation  may  be  con- 
fined to  one  tonsil,  but  more  often  involves  both.  When  the  exudate  is 
limited  to  the  tonsils  the  liability  to  secondary  systemic  infection  is  not 
very  great. 

In  the  severe  forms  of  diphtheria  the  exudate  spreads  beyond  the 
region  of  the  tonsils,  or  it  may  appear  simultaneously  on  various  parts 
of  the  fauces.  One  of  its  peculiarities  is  that  it  often  shows  itself  as 
small,  thick  patches  on  prominent  points,  such  as  the  end  of  the  uvula, 


THE  HYMI'TOMATOLOaV  OF  1)1 1'H'I'II Hlil A  {\2?> 

the  enl^e  of  tlie  ('])i^1otli,s,  the  cartilafjje  of  Wrisher^,  and  the  like.  It 
very  frecjuently  covcu's  c()inj)let<;ly  not  only  the  tonsils,  hut  tlie  anterior 
and  posterior  pihars,  the  pliaryngeal  wall,  the  uvula,  an(J  the  entire 
soft  palate.  In  severe  cases  it  is  not  uncommon  to  see  the  exudate  on 
the  vault  of  the  mouth  piled  up  so  high  as  to  form  a  thick  spongy  mass, 
seriously  interfering  with  deglutition.  At  the  time  of  writing  tliese  lines 
we  have  in  the  l)os[)ital  three  or  four  patients  in  whose  throats  this 
extensive  form  of  exudate  is  seen.  The  clinical  history  of  f>ne  of  these 
patients  is  as  follows: 

K.  R.,  aged  seven  years,  white,  female,  admitted  December  7th,  on 
ninth  day  of  the  disease.  On  the  first  and  second  days  in  the  hospital  the 
temperature  was  100° F.,  on  the  third  day  it  fell  to  y7;i°F.  The  pul.se 
ranged  from  104  to  112  per  minute  during  the  first  and  second  days,  and 
on  the  third  day  fell  to  82.  The  culture  was  positive.  On  admission 
the  exudate  covered  completely  and  thickly  both  tonsils,  the  anterior 
pillars,  the  pharyngeal  wall,  the  uvula,  and  the  greater  part  of  the  soft 
palate.  On  the  latter  it  was  piled  up  in  a  thick,  spongy  mass.  Deglu- 
tition was  difficult.  The  face  was  swollen,  pale,  and  glossy.  The  breath 
was  very  fetid.  Both  nares  contained  large  plugs  of  exudate,  and  were 
constantly  oozing  blood.  The  cervical  glands  on  both  sides  of  the  neck 
were  very  much  swollen.  Immediately  after  admission  the  patient 
received  4500  units  of  antitoxin;  twelve  hours  later  another  dose  of 
3000  units  was  given,  and  again  a  third  dose  of  4500  units,  making  in 
all  12,000  units.  Death  resulted  on  December  9th,  from  toxaemia 
and  exhaustion. 

We  have  seen  the  exudate  even  more  copious  than  in  the  case  just 
cited.  Cases  have  come  under  our  observation  in  v^^hich  not  only  the 
entire  fauces,  including  the  soft  palate,  were  covered,  but  even  the  hard 
palate  and  the  greater  part  of  the  buccal  cavity  also.  Sometimes  it 
appears  on  the  gums,  but  more  often  invades  the  edges  of  the  tongue. 
It  is  frequently  seen  in  the  pharyngeal  vault,  and  may  extend  into  the 
Eustachian  tubes.  The  nares  and  the  larynx  are  so  often  involved  that 
the  behavior  of  the  disease  in  these  cavities  will  subsequently  receive 
special  notice. 

The  exudate  is  usually  of  a  yellowish-white  or  cream  color,  but  it 
may  present  a  dark-gray  appearance.  Its  color  is  liable  to  be  changed 
by  the  ingestion  of  certain  drugs,  or  by  remedial  agents  employed 
locally.  It  sometimes  is  rendered  darker  by  having  coagulated  blood 
incorporated  with  it.  But  in  perfectly  typical  cases  it  does  not  look 
unlike  moist  chamois  skin.  Indeed,  when  large  fragments  or  casts  are 
exfoliated  and  floated  in  water  they  have  a  strong  resemblance  to  this 
material. 

The  exudate  may  be  thick,  or  thin  and  filmy.  When  very  thick  it 
may  be  seen,  even  at  quite  an  early  state,  lying  rather  loosely  on  the 
mucous  membrane,  or  partly  detached  at  its  margin,  especially  when 
located  on  the  soft  palate.  If  forcibly  removed  it  is  liable  to  be  repro- 
duced in  the  course  of  a  few  hours,  although  in  many  cases  it  exfoliates 
quickly  and  does  not  reform.    Instead  of  presenting  the  appearance  of 


624  '  DIPHTHERIA 

a  distinct  membrane  lying  upon  the  mucous  surface,  the  exudate  some- 
times forms  into  and  becomes  a  part  of  the  mucous  membrane  itself. 
In  this  case  there  is  a  grayish  discoloration  which  disappears  slowly,  and 
often  by  the  process  of  necrosis,  rather  than  by  exfoliation  of  the  mem- 
brane. Of  course,  this  process  is  followed  by  an  ulcerating  surface 
which  heals  by  granulation. 

The  involved  parts  of  the  fauces,  especially  the  uvula,  become  oedem- 
atous  and  swell  considerably.  After  the  exudate  has  disappeared  from 
the  uvula,  the  latter  is  apt  to  present  an  ulcerated  appearance,  and, 
through  loss  of  tissue,  is  not  infrequently  left  smaller  than  normal.  In 
all  severe  cases  in  which  there  is  oedema  and  swelling  of  the  fauces 
there  is  not  only  difficult  and  painful  deglutition,  but  the  respiration 
and  articulation  are  also  affected 

In  the  act  of  swallowing  it  is  not  uncommon  to  see  milk  regurgitated 
through  the  nares.  As  the  case  progresses  the  voice  becomes  distinctly 
nasal,  and  is  apt  to  continue  so  for  some  weeks. 

At  first  the  exudate  is  free  from  odor;  but  when  the  disease  is  severe 
a  distinct  odor  is  noticed  in  the  course  of  two  or  three  days.  Indeed, 
the  breath  of  the  patient  is  often  so  peculiarly  offensive  that  an  experi- 
enced clinician  might  be  led  to  suspect  the  nature  of  the  affection 
before  an  examination  of  the  throat  has  been  made.  In  septic  cases, 
when  decomposition  of  the  secretions  and  the  exudate  goes  on  rapidly, 
the  odor  is  in  the  highest  degree  offensive,  and  is  well  calculated  to 
excite  suspicion  that  extensive  necrotic  changes  of  the  tissues  may  be 
taking  place.  The  tissue  change,  however,  is  not  always  as  great  as 
the  odor  would  indicate.  A  copious  mass  of  exudate  is  often  thrown 
off  very  quickly  by  the  process  of  exfoliation,  leaving  the  parts  only 
slightly  ulcerated.  In  such  cases  the  odor  will  promptly  disappear, 
especially  with  the  use  of  cleansing  or  antiseptic  lotions.  With  this 
apparent  improvement  one  should  not  be  too  hasty  in  pronouncing  the 
patient  out  of  danger,  for  the  probabilities  are  that  the  most  critical 
period  of  the  disease  is  yet  to  be  encountered.  Where  the  mucous  lining 
of  the  fauces  is  at  all  destroyed,  leaving  the  absorbents  exposed,  the 
toxin  of  the  specific  micro-organisms  is  permitted  to  enter  the  circu- 
lation, and  the  subsequent  danger  from  toxaemia  is  far  greater  than 
the  primary  local  disease. 

While  there  is  usually  some  swelling  and  tenderness  of  the  cervical 
and  submaxillary  glands  at  an  earlier  stage  of  the  diphtherial  process, 
coincidently  with  intense  involvement  of  the  fauces,  these  glands, 
together  with  the  surrounding  areolar  tissue,  become  indurated  and 
infiltrated,  giving  rise  often  to  extensive  tumefaction.  The  face,  besides 
being  pale  and  sallow,  presents  also  a  swollen  and  glossy  appearance. 
As  the  exudate  and  septic  secretions  disappear  from  the  throat,  the 
tumefaction  of  the  neck  subsides.  Occasionally,  however,  the  cervical 
glands  take  on  suppurative  action,  but  not  so  frequently  as  in  scarlet 
fever. 

Nose. — Next  to  the  fauces  the  nose  is  the  most  common  site  of  the 
diphtheritic  process.     The  disease  not  infrequently  attacks  the  nares 


77//';  HVMI'TOMATOl.OdY  Oh'  1)1 1'llTII hlUI A  025 

primarily,  but  most  often  the  exudate  ext(>n(ls  I'rojii  (lif  (liro;it  io  flic 
nasal  cavities  l)y  way  of  the  posterior  aspect  of  the  uvula.  When  this 
occurs  the  posterior  wall  of  the  pharynx  is  also  liable  to  be  involved 
through  contiguity  of  structure.  At  first  there  is  but  little  discharge 
from  the  nares,  as  in  the  l)eginning  of  an  a(;ute  catarrh,  but  it  soon 
increases  and  becomes  Hoccnilent.  When  the  disease  has  fully  develofx-d, 
the  discharge  is  often  profuse  and  sometimes  fetid. 

Before  the  diphtherial  process  has  continued  very  long,  evidence  of 
copious  exudation  may  be  seen  by  inspecting  the  nares.  In  many  cases 
the  membrane  is  very  thick  and  dense,  and  o(;cludes  the  nasal  cavities 
completely.  There  is  then  but  little  discharge  from  the  external  orifices; 
but  the  voice  becomes  distinctly  nasal,  and  the  patient  is  obliged  to 
breathe  through  the  mouth. 

When  the  fauces  are  at  the  same  time  severely  involved,  the  respira- 
tion becomes  considerably  hampered,  and  there  is  also  difficult  deglu- 
tition, with  marked  restlessness  and  insomnia. 

The  amount  of  exudate  that  is  sometimes  expelled  from  the  nares 
is  enormous.  The  membrane  is  often  thrown  off  in  perfect  casts,  and 
on  inspecting  these  one  is  apt  to  feel  surprised  that  so  much  material 
could  have  been  contained  within  the  nasal  cavities.  When  the  exudate 
begins  to  separate,  or  has  been  either  partly  or  wholly  cast  off,  the 
discharge  usually  returns,  and  is  often  sanguinopurulent  in  character. 
There  is  no  form  of  diphtheria  more  dangerous  than  that  of  the  nares. 
The  injury  sustained  by  the  capillary  bloodvessels  prepares  the  way 
for  rapid  absorption  of  the  toxins,  the  effects  of  which  are  apt  to  become 
painfully  visible  in  a  short  time.  Not  only  is  systemic  poisoning  seen, 
but  the  more  common  sequelae  of  diphtheria  most  often  follow  the  nasal 
form  of  the  disease. 

Epistaxis  is  of  frequent  occurrence  even  in  mild  cases;  but  when 
the  diphtheritic  involvement  is  intense  the  hemorrhage  from  the  nose 
is  liable  to  occur  repeatedly,  as  the  disease  progresses,  and  may  prove 
to  be  a  very  troublesome  symptom.  In  some  cases  there  is  a  constant 
oozing  of  blood,  while  in  others  the  hemorrhage  is  sometimes  so  free 
as  to  be  the  immediate  cause  of  death. 

In  the  severest  form  of  nasal  diphtheria  the  nose  is  slightly  reddened 
externally,  and  moderately  swollen  or  oedematous.  The  face  also  is 
oedematous,  remarkably  pale,  and  has  a  peculiar  glistening  appearance. 
The  pulse  is  usually  feeble,  the  circulation  bad,  vomiting  often  occurs, 
and  not  infrequently  there  is  marked  drowsiness.  Indeed,  the  symptoms, 
taken  together,  are  such  as  would  indicate  profound  systemic  poisoning. 
Many  patients  in  this  condition  die  at  a  comparatively  early  stage  of 
the  disease. 

In  the  more  favorable  cases  the  exudate  is  thrown  oft'  en  masse  in 
the  form  of  casts,  and  the  constitutional  symptoms  do  not  become  so 
pronounced.  But  one  should  not  feel  too  sanguine  of  recovery  in  any 
case,  for  danger  of  the  development  of  toxaemia  is  never  absent.  Even 
when  this  serious  condition  does  not  arise,  and  the  general  symptoms 
seem  most  favorable,  still  there  is  a  strong  liability  that  the  aftection 

40 


626  DIPHTHERIA 

may  be  followed  by  paralysis,  either  partial  or  general.  Postdiphtheritic 
paralysis  is  more  common  after  the  nasal  form  of  the  disease  than  after 
any  other  variety. 

Nasal  diphtheria  sometimes  assumes  the  form  of  chronic  rhinitis. 
In  such  cases  there  is  usually  a  discharge  from  the  nares  and  often 
excoriation  of  the  skin  about  the  nose.  But  the  affection  may  persist 
for  months,  with  little  or  no  nasal  discharge.  Persons  thus  afflicted 
often  unwittingly  spread  diphtheria.  It  is  important  that  such  cases 
should  be  recognized  and  treated,  and  even  isolation  should  be  advised 
until  a  cure  is  effected  and  the  specific  organisms  have  disappeared.  It 
is  only  by  the  aid  of  bacteriology  that  this  form  of  diphtheria  can  be 
definitely  determined. 

Middle  Ear. — From  the  pharyngeal  vault  the  exudate  sometimes 
spreads  by  way  of  the  Eustachian  tube  to  the  middle  ear,  causing  an 
acute  median  otitis.  This  is  often  unattended  by  pain;  hence  the  con- 
dition may  not  be  recognized  until  suppuration  takes  place  and  the 
tympanum  has  ruptured.  The  purulent  discharge  which  flows  from 
the  meatus  will  show  the  presence  of  the  bacilli  of  diphtheria  associated 
with  certain  other  organisms,  such  as  streptococci  and  staphylococci. 
There  is  usually  some  rise  of  temperature,  often  assuming  a  septic 
character. 

The  otorrhoea  frequently  persists  a  long  time,  but  is  seldom  followed 
by  permanent  deafness.  Temporary  deafness,  however,  may  be  seen 
as  the  result  of  a  paretic  condition  of  the  muscles  of  the  Eustachian 
tube  and  of  the  tympanum.  Only  in  rare  instances  are  the  changes 
in  the  intratympanic  cavity  so  great  as  to  cause  permanent  deafness. 
This  is  not  so  likely  to  happen  in  diphtheria  as  in  scarlet  fever. 

Eyes. — Diphtheritic  involvement  of  the  conjunctiva  is  not  very  fre- 
quently seen.  It  occurs  sometimes,  but  the  wonder  is  that  it  is  not  more 
common  in  children,  since  they  so  often  convey  the  infectious  discharges 
from  the  nares  to  their  eyes  by  means  of  their  hands.  Physicians  and 
nurses  who  work  among  diphtheria  patients  are  frequently  subjected  to 
the  risk  of  infection  by  having  the  secretions  from  the  throats  of  such 
patients  coughed  into  their  eyes.  While  we  have  sometimes  seen  a  mild 
conjunctivitis  occur  from  this  accident  we  have  never  known  it  to 
assume  a  diphtheritic  character,  though  such  a  result  is  not  impossible. 

It  has  been  suggested  by  some  writers  that  the  diphtheritic  inflam- 
mation may  extend  to  the  conjunctiva  by  way  of  the  tear  duct,  but 
this  we  believe  is  of  rare  occurrence.  As  an  unhealthy  mucous  mem- 
brane is  more  prone  to  diphtherial  infection,  it  is  therefore  probable  that 
an  acute  or  chronic  inflammation  of  the  eyes  furnishes  a  predisposition 
to  eye  involvement  when  diphtheria  occurs  in  a  child  thus  afflicted. 

When  the  conjunctiva  becomes  involved  the  membrane  usually 
spreads  rapidly  from  one  eyelid  to  the  other,  and  the  bulbar  conjunctiva 
is  almost  always  greatly  chemosed.  The  exudate  is  first  seen  as  flocculi, 
but  it  rapidly  forms  into  a  thick  membrane,  so  thick,  indeed,  as  to  press 
hard  upon  the  cornea,  causing  it  to  become  hazy  and  often  undergo 
a  destructive  necrosis.    When  the  cornea  of  the  eye  becomes  weakened 


77//';  SYMPTOM ATOIJXIV  OF  1)1 1'llTII HKI A 


(■,27 


or  perforated  by  lliis  pnH-css  (lie  iris  i)rolapses.  J)uring  tli<-  foursc  of 
the  disease  (lie  eyelids  swell  and  stiU'en,  so  that  it  is  ainiost  iinjjfjssihie 
to  ins])e('t  the  vyc,  itself.  From  wliat  has  heeii  said  it  is  evident  that 
loss  of  vision  is  iniininent. 

Fortunately  the  affection  is  not  always  so  destructive  In  thr  mildci- 
cases  recovery  may  take  place  without  impairment  of  vision.  I>iif  \vl,<ii 
the  disease  is  so  severe  as  to  cause  the  destruction  of  hoth  eyes,  tiie 
patient's  life  is  placed  in  great  jeopardy.  All  such  cases  that  have  come 
under  our  observation  have  died. 

Skin. — The  diphtheritic  membrane  may  appear  on  abraded  surfaces 
of  the  skin,  but  this  is  by  no  means  so  common,  even  in  the  worst  forms 

Fio. n2 


Diphtheritic  involvement  of  the  mucous  membrane  of  the  eyelids,  showing  thick,  co])ious  exu- 
date on  the  inner  surfaces  of  the  lids,  cedema  of  the  face,  and  swelling  of  the  glands  of  the  neck. 
Vision  was  destroyed  and  death  ensued. 


of  diphtheria,  as  has  been  supposed.  It  is  only  in  the  wound  of  the 
skin  from  the  operation  of  tracheotomy  that  this  condition  occurs  with 
any  degree  of  frequency.  But  even  here  the  diphtheritic  membrane 
appears  less  often  than  one  would  suppose.  We  have,  however,  known 
the  membrane  to  appear  on  the  prepuce  of  a  child  who  developed 
diphtheria  immediately  after  circumcision. 

Some  writers  describe  a  rash  that  is  sometimes  seen  as  the  result  of 
diphtheria.  It  is  said  that  it  may  appear  at  an  early  stage  of  the  disease, 
and  that  it  is  erythematous  in  character.  It  is  described  as  either 
localized  and  evanescent,  being  scarcely  visible  for  more  than  a  few 
hours,  or  as  covering  a  large  surface  of  the  skin  and  remaining  for 
some  days.      We   must    confess    that    we  are    not    familiar   with    any 


628  DIPHTHERIA 

rash  that  can  be  said  to  be  pathognomonic  of  diphtheria.  When  a 
circumscribed  or  diffuse  rash  of  punctiform  character  is  present,  one 
should  think  of  scarlatinal  infection,  for  scarlet  fever  and  diphtheria 
not  infrequently  coexist.  The  former  disease  cannot  necessarily  be 
excluded  because  the  body  temperature  is  low.  Over  and  over  again 
we  have  seen  these  diseases  coexist  when  the  temperature  was  but 
little  above  normal. 

CEdema.— Oedema  of  the  face  and  some  other  parts  of  the  body  is 
sometimes  seen  as  the  result  of  intense  systemic  poisoning,  and  quite 
independent  of  disease  of  the  kidneys. 

In  the  worst  forms  of  diphtheria  it  is  not  uncommon  to  find  petechiee, 
purpuric  discolorations,  and  ecchymoses.  The  latter  may  occur  spon- 
taneously, or  result  from  the  slightest  bruise. 

Antitoxin  rashes,  so  common  since  this  agent  has  come  into  use, 
are  postponed  for  consideration  under  the  head  of  the  antitoxin  treat- 
ment of  diphtheria. 

Toxaemia. — A  peculiar  train  of  symptoms  often  results  from  absorp- 
tion of  the  toxin  elaborated  by  the  specific  organisms  of  diphtheria. 
These  symptoms  are  so  peculiar  that  one  who  is  at  all  familiar  with 
them  would  seldom  fail  to  associate  them  with  diphtheria,  even  in  the 
absence  of  any  other  clinical  manifestations  of  this  disease.  They 
often  follow  the  disappearance  of  the  exudate  in  the  nose  and  throat, 
making  their  appearance  at  a  time  when  the  physician  may  feel  that 
his  patient  is  on  the  straight  road  to  recovery. 

When  symptoms  of  toxaemia  occur,  they  usually  make  their  appear- 
ance during  the  second  week  of  the  illness.  They  may,  however,  be  seen 
a  little  earlier  or  a  little  later.  Frequently  about  the  time  the  exudate 
has  disappeared  the  patient  commences  to  vomit,  and  the  stomach 
becomes  so  irritable  that  everything  is  ejected  almost  as  soon  as 
swallowed.  Pallor  at  once  is  noticed,  and  this  rapidly  increases,  giving 
the  face  a  remarkably  blanched  appearance.  The  change  of  color  to 
a  pale,  waxy  hue  is  sometimes  so  sudden  as  to  come  in  the  nature  of 
a  surprise.  Coincidently  with  these  symptoms  the  pulse  becomes  weak 
and  often  irregular.  It  may  be  either  slow  or  rapid.  The  force  of  the 
apex  beat  of  the  heart  is  diminished,  and  the  first  sound  indistinct. 
As  the  case  progresses,  the  pulse  becomes  weaker  and  slower,  often 
not  more  than  40  to  50  per  minute.  The  extremities  are  cold.  The 
mind  is  clear,  but  the  patient  shows  an  anxious  expression.  Albumin 
is  most  always  found  in  the  urine.  The  temperature  is  apt  to  be  low, 
often,  indeed,  subnormal. 

When  toxaemia  is  not  profound  the  symptoms  may  gradually  improve 
and  recovery  follow.  But  the  condition  of  the  patient  should  always 
be  regarded  as  extremely  critical.  Often  the  signs  of  improvement  are 
more  apparent  than  real.  For  example,  a  patient  may  be  entirely 
conscious,  converse  intelligently,  sit  up  in  bed  and  take  nourishment, 
and,  despite  this  apparent  improvement,  fall  over  and  die  almost 
instantly  of  heart-failure.  More  frequently,  however,  death  comes 
gradually,  and  is  almost  invariably  preceded  by  precordial  pain.    The 


77//';  HYM I'TOMATOIJXIY  OF  1)1 1'llTII irnl A  {]l\) 

heart  soinids  become  less  und  less  distiiicl,  jiikI  tlic^  pulse  {(rows  more 
aiul  more  feeble  niitil  it  is  absolutely  lost.  It  is  not  rare  for  a  i>atier)t 
to  live  for  hours,  sometimes  even  a  day  or  tw(i,  with  no  peree[)tible 
pulse  at  the  wrist.  It  is  remarkable  to  note  that  consciousness  in  this 
condition  is  usmdly  retained  to  the  last. 

Septic  Diphtheria. — In  diphtheria  there  are  always  associated  with 
the  specific  micro-organisms  streptococci  and  staphylococci  in  {^reat 
abundance,  and  the  latter  often  give  rise  to  a  concurrent  septic  infection 
which  constitutes  an  important  factor  in  the  course  of  the  disease. 
It  is  sometimes  difficult  to  determine  to  what  extent  this  secondary 
infection  is  responsible  for  results,  as  distinguished  from  those  of  the 
primary  infection.  Doubtless  in  many  cases  of  diphtheria  streptococcus 
infection  is  the  principal  cause  of  death. 

Septic  infection  is  most  liable  to  occur  in  patients  with  intense  nasal 
involvement,  and  in  whose  fauces  the  exudate  assumes  a  dirty-gray 
or  brownish  appearance.  Instead  of  becoming  detached  and  peeling 
off  en  masse,  the  exudate  breaks  down  into  a  semisolid  or  gnmious 
mass.  In  such  cases  the  decomposing  and  liquefying  membrane  gives 
rise  to  an  offensive  discharge  from  the  nares  and  mouth,  and  a  fetid 
breath.  This  discharge,  ichorous  in  character,  causes  reddening  and 
excoriation  at  the  orifices  of  the  nose  and  corners  of  the  mouth,  and 
the  denuded  surfaces  are  often  converted  into  ulcers  v/hich  quickly  take 
on  a  dirty-gray  coating.  Sometimes  there  is  considerable  ulcerative 
action  seen  in  the  fauces  and  nares,  but,  strange  to  say,  this  process  is 
commonly  limited  to  the  mucous  membrane.  It  is  only  in  rare  cases 
that  the  subepithelial  tissue  is  lost  to  a  greater  exteht  than  would  result 
from  a  small  ulcer  here  and  there.  These  ulcers  are  apt  to  remain 
covered  for  a  long  time  with  a  yellowish  coating. 

The  disorganization  of  the  mucous  membrane  of  the  affected  parts 
is  commonly  attended  with  capillary  hemorrhages,  more  or  less  marked. 

As  might  be  supposed,  the  color  of  the  false  membrane  is  changed  by 
its  becoming  infiltrated  with  blood.  When  the  hemorrhages  are  copious, 
and  the  blood  is  poured  out  between  the  mucous  membrane  and  the 
exudate,  the  latter  is  quite  sure  to  be  separated  to  a  considerable  extent. 
It  is,  therefore,  not  unusual  to  find  in  such  cases  a  good  deal  of  loose 
exudate  in  the  throat,  and  in  the  nose  also,  undergoing  rapid  decom- 
position. 

As  the  result  of  septic  infection,  the  lymph  glands  of  the  neck  become 
inflamed  and  swollen.  The  periglandular  connective  tissue  may  also 
inflame  and  swell  to  a  certain  degree.  In  some  cases  the  swelling  is 
so  great  that  the  neck  is  raised  to  an  even  line  with  the  face.  The  skin 
becomes  tense,  smooth  and  shining,  and  may  either  feel  doughy  to  the 
touch  or  as  dense  as  a  board.    Suppuration  may  or  may  not  result. 

Attention  has  already  been  called  to  the  fact  that  in  septic  cases  a 
rash  is  apt  to  appear  on  the  skin.  The  rash  may  at  first  be  erythematous 
or  slightly  macular,  but  as  the  disease  progresses  it  often  assumes  a 
petechial  character. 

In  this  form  of  diphtheria  the  temperature  runs  comparatively  high — • 


630 


DIPHTHERIA 


ranging  from  102°  to  104°  F.  There  is  usually  considerable  variation 
between  the  morning  and  evening  records.  The  pulse  is  rapid  and 
feeble,  and  the  extremities  are  often  cool.  Suppuration  of  the  middle 
ear  is  liable  to  occur,  and  pneumonia  sometimes  develops. 

Children,  restless  at  first,  become  apathetic  later  on,  which  condition 
increases  until  death  supervenes.  Death,  however,  is  not  the  inevitable 
result,  for  the  milder  cases  frequently  recover. 

Fever. — Except  at  the  onset  of  diphtheria,  fever  is  not  a  prominent 
symptom.  The  disease  almost  always  begins  with  fever,  more  or  less 
intense.     In  the  milder  cases  the  temperature  of  the  body  may  not  rise 


Fjg.  93 


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B.  G.,  ordinary  type  of  diphtheria,  occurring  in  a  child  five  years  of  age,  showing  a  high  initial 
temperature  with  a  rapid  decline. 


much  above  the  normal,  but  in  the  severer  cases,  during  the  first  day 
or  two  of  the  disease,  it  usually  ranges  from  101°  to  102°  F.;  but  after 
the  full  appearance  of  the  exudate— that  is,  after  the  second  or  third  day 
— the  temperature  commonly  drops  to  normal,  and  sometimes  below. 
Our  experience  accords  with  that  of  Lennox  Browne,  who  says:  "Of 
1000  cases  which  came  under  observation,  on  an  average,  on  the  third 
day  of  the  diphtherial  attack,  the  temperature  in  80  per  cent,  was  101°; 
while  in  50  per  cent,  the  average  temperature  during  its  course  was 
below  99°." 
As  already  stated,  the  average  temperature  in  the  septic  form  of 


TlIK  ^YMI'TOMATOIJJdY  OK  1)1 1'llTllEIilA 


iuW 


diphtlieriii  is  always  (:onif)aratively  \\\li:}\,  wliilf  in  \\\c  fox;rrr)if;  cases  it 
falls  to  normal  and  ev(m  lower. 

In  acute  adenitis,  which  often  occurs  as  a  cojnplieatioji  in  di|)htheria, 
the  temperature  ranges  high,  sometimes  to  the  extent  of  i(J'1^  to  MWy"  V. 
[f  suppuration  takes  place  and  the  pus  is  liberated  the  hyperpyrexia 
at  once  subsides.  In  every  case  of  continued  liigh  temperature  one 
should  suspect  the  existence  of  some  complication.  'V\\v  degree  f>f  fev(;r, 
under  such  a  circumstance,  is  usually  not  did'crent  from  that  which  is 
characteristic  of  the  associated  disease. 

What  has  been  said  of  the  temperature  in  ordinary  diphtheria  does 
not  apply  with  equal  force  to  the  laryngeal  form  of  the  disease.  In  this 
class  of  cases,  instead  of  falling  after  the  first  two  or  three  days  of  ill- 
ness, it  frequently  continues  high,  especially  when  intubation  is  required 


Fig.  94 


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.luno  July 

M.,  aged  five  and  one-half  years  ;  septic  type  of  diphtheria  in  a  patient  with  copious  exudate 
in  the  throat ;  swollen  cervical  glands,  later  suppurating.    Recovery. 


for  relief  of  the  stenosis,  and  while  the  tube  is  in  the  larynx.  In  the 
majority  of  such  cases  the  temperature  continues  at  101°  to  102°  F. 
for  a  number  of  days.  If  bronchopneumonia  develops,  which  is  not 
an  infrequent  comphcation,  the  temperature  will  continue  high  for  an 
uncertain  length  of  time. 

Circulatory  Symptoms. ^ — In  all  well-marked  cases  of  diphtheria  the 
pulse  is  frequent.  Its  rapidity,  indeed,  may  be  out  of  proportion  to 
the  temperature.  In  severe  cases,  especially  in  children,  the  pulse 
ranges  between  120  and  160  per  minute,  and,  as  the  disease  progresses, 
becomes  irregular  and  weak.  The  apex  beat  of  the  heart  is  often 
diminished  in  intensity  and  the  first  sound  becomes  indistinct.  Atten- 
tion has  already  been  called  to  the  fact  that  the  action  of  the  heart 
is  greatly  influenced  by  the  profound  asthenia  resulting  from  toxaemia. 


632 


DIPHTHERIA 


An  abnormally  slow  pulse  is  of  grave  import,  and  will  be  referred  to 
again  when  considering  the  question  of  prognosis. 


Fig. 

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C.  S,,  case  of  laryngeal  diplitheria  of  average  severity  admitted  to  the  Municipal  Hospital  on 
the  third  day  of  the  disease,  showing  decline  of  temperature  after  removal  of  the  intubation  tube. 
Recovery. 

The  Urine. — In  the  milder  cases  no  marked  change  is  found  in  the 
urine,  either  in  the  quantity  voided  or  its  constituents.  In  severe  cases 
it  contains  an  excess  of  urea,  and  sometimes  epithelial  cells  and  casts. 
Hsematuria  is  much  less  common  than  in  scarlet  fever.     Albumin  in 


77//';  ^YMr'rOMATOIJXIY  Oh'  l>ll'IITIII':iaA  {Y.\:\ 

small  (|tiiiiil,i(i('S  is  found  ii)  a-  hir^c.  profxtrlion  of  cases.  It  is  said  io 
be  present  in  nhoul  one-third  of  all  cases;  hut  t[)is  estirnate  is,  according 
to  our  experience,  much  too  low.  Some  writers  believe  that  albumin 
is  more  often  found  since  antitoxin  has  come  into  use.  Suppression  of 
urine  and  ura'mic  symptoms  are  rare.  This  subject  will  be  n;ferred  to 
afijain  when  considering;  the  complications  of  diphtheria. 

Nervous  Symptoms. — In  the  acute  stage  of  ch'phtheria  nervous 
symptoms  are  not  a  prominent  feature  of  the  disease.  Convulsions 
sometimes  occur  as  an  initial  symptom  in  (children  of  nervous  tempera- 
ment. In  fatal  cases  convulsive  movements  are  not  infrequent  in  the 
death  stru<2;<i^le.  Delirium  occurs  only  in  exceptional  instances,  and, 
when  present,  is  usually  mild.  Children,  as  a  rule,  sleep  well;  they 
often,  indeed,  lapse  into  a  state  of  apathy  or  stupor. 

Paralysis  of  the  palate  is  often  seen  during  the  acute  stage,  or,  at  least, 
before  the  exudate  has  entirely  disappeared  from  the  fauces.  We  have 
frequently  noticed  its  presence  as  early  as  the  seventh  to  the  tenth  flay 
of  the  diphtherial  attack.  Its  existence  is  manifested  by  slight  difhculty 
in  deglutition,  and  by  a  nasal  tone  of  the  voice.  Also,  at  an  early  stage 
of  the  disease,  the  cardiac  nerves  may  become  involved,  giving  rise  to 
cardiac  syncope,  which  is  a  common  cause  of  sudden  death.  General 
paralysis  frequently  occurs  during  convalescence.  This  will  receive  due 
consideration  under  the  head  of  sequelse. 

Laryngotracheal  Diphtheria,  or  Membranous  Croup.— This  form  of 
diphtheria  may  be  described  as  a  pseudomembranous  exudation  into 
the  larynx  and  trachea,  giving  rise  to  symptoms  of  croup.  It  owes  its 
origin  to  the  same  specific  cause  that  is  operative  in  producing  diph- 
theria of  the  fauces  and  nares,  namely,  the  Klebs-LoeflBer  bacillus. 
Before  this  organism  was  discovered  and  definitely  shown  to  be  the 
material  etiological  factor  of  diphtheria  exudation,  it  was  pardonable 
to  have  considered  membranous  croup  as  the  result  of  a  non-specific 
laryngotracheal  inflammation.  It  is  certainly  no  longer  permissible 
to  speak  of  an  idiopathic  catarrhal  croup,  except  as  applied  to  a  spas- 
modic affection  of  the  larynx  of  an  entirely  different  character.  Catarrhal 
croup  is  quite  free  from  danger,  and  non-contagious. 

It  must  be  admitted,  however,  that  pseudomembrane  may  form  in 
the  larynx,  as  on  the  tonsils,  from  microbic  causes  in  which  the  Klebs- 
Loeffler  bacilli  have  no  part.  The  streptococcus  is  the  particular  micro- 
organism found  in  this  condition,  and  is  believed  to  be  responsible  for 
the  membrane,  although  the  staphylococcus  has  been  found  as  well. 
The  symptoms  caused  by  an  exudation  in  the  larynx  due  to  these 
organisms  are  precisely  the  same  as  those  caused  by  the  genuine  ba ciliary 
exudation.  If  differentiation  be  possible,  it  is  only  by  the  aid  of  bacterio- 
logical examination. 

Our  experience  leads  us  to  believe  that  an  exudation  into  the  larynx 
and  trachea  of  streptococcic  origin  is  rare.  While  admitting  the  possi- 
bility of  such  an  occurrence,  it  is  certainly  safer,  both  for  the  patient 
and  the  public,  to  regard  and  treat  all  cases  of  membranous  croup  as 
genuine  diphtheria. 


634  DIPHTHERIA 

Some  authors  teach  that  in  diphtheria  the  exudation  rarely  occurs  pri- 
marily in  the  larynx  and  trachea,  believing  that  it  invades  these  parts 
by  downward  extension.  This  is  undoubtedly  true  of  most  cases,  but  we 
have  frequently  seen  membranous  croup  in  children  whose  fauces  and 
nares  were  entirely  free  from  membrane.  Some  of  the  worst  cases  are 
of  this  description.  Our  experience  warrants  the  statement  that  in  fully 
one-half  of  all  cases  there  is  only  scanty  exudation  in  the  fauces.  It  is 
often  seen  only  on  the  tonsils  in  the  form  of  dots,  but  may  present  a 
scattered  appearance  on  the  adjacent  parts.  In  many  instances  the 
exudation  will  be  found  at  the  outskirts  of  the  larynx  on  the  lateral 
glossoepiglottic  folds. .  The  epiglottis  is  frequently  involved.  Lennox 
Browne  believes  that  the  epiglottis  is  almost  invariably  first  attacked, 
and  seldom  escapes.  His  experience  leads  him  to  believe  that  it  is  the 
rule,  when  the  larynx  is  involved,  for  the  exudation  to  begin  on  some 
parts  of  the  fauces  and  extend  downward. 

While  laryngeal  symptoms  often  constitute  the  first  evidence  of 
diphtheria  in  children,  there  are  many  instances  of  the  disease  beginning 
in  the  fauces  and  nares  and  continuing  for  several  days  in  a  severe  form 
before  the  larynx  becomes  involved.  This  has  been  called  descending 
diphtheria.  In  this,  and,  indeed,  every  form  of  the  disease,  the  exudation 
may  extend  into  the  trachea,  the  bronchi,  and  even  into  the  bronchioles 
(Fig.  96). 

Cases  of  ascending  croup  have  been  described;  that  is  to  say,  the 
exudation  beginning  in  the  bronchi  has  extended  upward  into  the 
trachea  and  larynx.  This  cannot  be  proved,  and  it  is  doubtful  whether 
it  ever  occurs. 

Symptoms. — When  diphtheria  exudation  invades  the  larynx,  the 
symptoms  vary  somewhat  according  to  the  age  of  the  patient.  In 
children,  in  whom  the  lumen  of  the  larynx  is  small,  symptoms  of  impaired 
breathing  soon  appear.  The  symptomatology  may  be  divided  into  three 
stages,  according  to  the  development  of  the  disease.  In  the  first  stage 
the  symptoms  consist  of  cough  and  hoarseness,  in  the  second  of  aphonia 
and  dyspnoea,  and  in  the  third  of  suffocation  and  asphyxia,  speedily 
ending  in  death  if  relief  be  not  afforded.  It  must  not  be  supposed  that 
all  three  stages  are  seen  in  every  case,  for  there  are  undoubtedly  instances 
of  abortive  croup. 

When  the  larynx  is  primarily  attacked,  the  disease  at  first  is  often 
thought  to  be  nothing  more  than  a  common  cold;  but  as  it  progresses 
its  real  nature  becomes  apparent.  There  is  always  cough,  more  or  less 
pronounced,  and  it  soon  becomes  hoarse  and  high-pitched,  with  a  shrill, 
metallic  sound.  Hoarseness  and  huskiness  of  the  voice  exist  with 
some  discomfort  in  the  throat,  and  moderate  fever.  As  the  exudation 
increases  the  voice  becomes  less  and  less  distinct,  and  often  loses  its 
sonorous  character.  Frequently,  at  an  early  stage  of  the  disease,  the 
symptoms  do  not  prevent  the  child  from  getting  out  of  bed  and  playing, 
even  when  there  may  be  some  evidence  of  beginning  dyspnoea.  In  one, 
two,  or  three  days  marked  disturbance  of  the  respiration  is  noticed, 
often  sufficient  to  cause  grave  apprehension.     The  obstruction  of  the 


77//';  HVMI'TOMATOIJXIY  Oh'  1)1 1'll'I'll h'.UI A 


03.0 


larynx,  due  to  cxiulntion  and  swelling,  is  sonK^limos  inc;r('as(;d  by  sjja.srn 
of  the  laryngeal  iniiscles.  As  the  disease  advances  respiration  becomes 
more  and  more  difhcult,  until  distressing  dyspncjea  supervenes.  The 
inspired  air  is  insuincient  to  fully  expand  the  lungs,  which  is  evident 
from  the  sinking  in  of  the  lower  end  of  the  sternum  and  tlie  lower  ribs 
at  each  act  of  insj)iriition.  '["hv.  blood  is  insnflic;iently  oxygenated,  as 
denoted  by  a  livid  hue  of  the  skin.  The  child  is  restless,  cannot  sleep, 
constantly  changes  its  position  in  bed,  and  vainly  looks  in  every  direction 


A  cast  of  exudate  expelled  from  the  upper  air  passages  by  coughing.    The  cast  extended  from 
the  larynx  downward  into  the  subdivisions  of  the  right  and  left  bronchi. 

for  relief.     One  does  not  often  see  a  more  pitiable  sight  than  a  little 
child  suffering  from  well-developed  membranous  croup. 

In  describing  these  symptoms  Lennox  Browne  truly  says:  "Each  in- 
spiration is  attended  by  a  peculiar  stridor  which  constitutes  one  of  the 
most  marked  characteristics  of  the  disease.  This  stridor  has  been  vari- 
ously described  as  high-pitched,  piping,  shrill,  metallic,  sibilant,  and 
wheezing.  During  the  dyspnoea  there  is  indrawing  of  all  the  muscles  of 
the  suprasternal  and  substernal  regions,  as  also  of  the  epigastrium,  the 
false  ribs,  and  even  the  lower  portion  of  the  sternum  itself;  of  all  those 


636  DIPHTHERIA 

parts,  in  fact,  which  would  generally  be  distended  in  healthy  inspiration. 
All  the  inspiratory  muscles,  regular  as  well  as  auxiliary,  are  observed 
during  the  spasm  to  work  painfully;  the  dilated  nostrils,  the  terrorized 
expression  of  the  face,  and  convulsive  movements  of  the  limbs,  all  giving 
evidence  of  a  laborious  and  futile  struggle  for  breath.  The  complexion 
becomes  cyanotic,  and  death  from  apnoea  appears  imminent,  and  may 
even  occur.  Should  membrane  be  coughed  up  there  may  be  a  favorable 
termination  to  the  dyspnoea,  when  the  metallic  sound  of  the  cough  will 
be  observed  to  change  to  that  of  a  bronchitis  or  remitting  laryngitis." 

Laryngeal  diphtheria  is  by  far  less  common  in  adolescent  and  adult 
persons,  and  much  less  fatal,  because  the  danger  from  stenosis  is  not 
so  great.  The  greater  development  of  the  larynx  in  persons  of  mature 
years  permits  of  some  diminution  of  its  aperture  without  affecting 
seriously  the  respiratory  act.  We  have,  however,  met  with  a  few  instances 
in  which  the  mechanical  obstruction  was  so  great  as  to  demand  operative 
interference.  When  the  exudation  is  limited  to  the  larynx  intubation 
will  afford  relief,  but  when  the  trachea  is  also  involved  tracheotomy 
is  to  be  preferred. 

In  membranous  croup  the  temperature  is  usually  higher  than  in 
faucial  diphtheria.  While  the  intubation  tube  is  being  worn  the  temper- 
ature is  liable  to  remain  two  or  three  degrees  above  the  normal. 

The  laryngotracheal  form  of  diphtheria  has  a  decidedly  local  char- 
acter, and  is,  therefore,  not  so  liable  to  be  attended  with  symptoms  of 
systemic  poisoning.  Toxaemia  and  general  paralysis  are  not  often  seen 
in  this  form  of  the  disease  when  it  is  strictly  localized.  The  infrequency 
of  constitutional  symptoms  may  be  accounted  for  by  the  comparative 
absence  or  scantiness  of  lymphatics  in  the  larynx  and  trachea.  Apart 
from  the  stenosis,  the  principal  source  of  danger  in  membranous  croup 
is  from  capillary  bronchitis  or  bronchopneumonia. 

THE  COURSE,  DURATION,  AND  TERMINATION  OF    DIPHTHERIA. 

In  m,ild  cases  of  diphtheria  the  local  lesions  are  moderate  in  degree 
and  the  constitutional  symptoms  not  serious.  The  exudation  is  scanty 
and  limited  to  the  tonsils.  At  the  onset  the  temperature  usually  rises 
two  or  three  degrees,  sometimes  a  little  higher,  but  quickly  falls  to  near 
the  normal.  The  mucous  membrane  of  the  fauces  is  congested,  and 
deglutition  slightly  painful.  There  is  usually  loss  of  appetite  and  some 
prostration.  The  pulse  rate  is  accelerated — the  rapidity  at  times  being 
out  of  proportion  to  the  rise  of  temperature. 

In  this  purely  local  form  of  the  disease  the  height  is  reached  in  from 
two  to  four  days,  when  all  the  symptoms  begin  to  subside.  The 
exudation  disappears,  and  the  small  areas  of  superficial  ulceration  left 
behind  rapidly  heal.  In  from  four  to  seven  days  the  fauces  assume 
their  normal  appearance,  and  the  patient  expresses  himself  as  feeling 
well,  although  there  is  apt  to  be  some  loss  of  strength  and  anaemia. 
Sequelae  are  extremely  rare. 

In  the  severe  type  of   diphtheria  the  constitutional  symptoms  are 


TJIK  aOUHHK,  DURATION,  AND  TI'lUM I N ATION  OF  Dl I'lmi IIHI A      (■,:>,7 

usually  well  marked  from  the  hcfrinriin^.  'Vhv,  tcmperaturf-  runs  up 
quickly  to  102°  or  l():i'^  F.,  there  is  loss  of  appetite,  the  tliroat  is  painful, 
and  the  child  is  restless  and  unable  to  sleep  long  at  a  time,  (^,'hilly 
sensations  may  be  experienced,  and  oc(;asionally  convulsions  occur. 

When  an  early  examination  of  the  throat  is  made  the  mucous  mem- 
brane will  be  found  to  l)e  of  a  vivid-red  color,  with  moderate  swelling 
of  the  parts.  The  uvula  soon  becomes  (x.'dematous,  elongated,  and 
swollen.  This  inflammatory  action  does  not  continue  long,  perhaps 
only  a  few  hours,  until  the  exudate  appears.  In  its  earliest  manifestation 
it  presents  the  form  of  grayish  or  yellowish-white  spots  of  pinhead  size. 
These  form  into  groups  which  (juickly  coalesce,  and  thus  develop  into 
large  patches.  In  most  cases  the  exudation  is  first  seen  on  the  tonsils 
and  rapidly  spread  to  other  parts  of  the  fauces.  Frequently,  in  twenty- 
four  to  forty-eight  hours  it  covers  not  only  the  tonsils,  but  the  anterior 
pillars,  the  uvula,  and  a  large  part  of  the  soft  palate.  With  this  increase 
of  exudation  the  temperature,  strange  to  say,  often  falls  one  or  two 
degrees.  The  lymphatic  glands  of  the  neck,  near  the  angle  of  the  jaw, 
are  almost  always  swollen. 

In  favorable  cases  the  local  symptoms  reach  their  maximum  develop- 
ment in  forty-eight  hours,  and  after  remaining  stationary  for  a  day  or 
two  begin  to  subside.  The  exudation  sometimes  exfoliates  in  large 
masses,  and  at  other  times  melts  away  little  by  little.  When  it  becomes 
detached  and  peels  off  it  may  disappear  entirely  in  from  six  to  eight 
days,  sometimes  sooner;  but  when  it  melts  away  gradually,  a  longer 
time  is  required.  The  mucous  membrane  of  the  parts  involved  is  left 
reddened,  and  shows  superficial  ulcerations.  Often  the  uvula  suffers 
the  greatest  loss  of  substance  from  the  ulcerative  action,  as  it  is  honey- 
combed, shrivelled,  and  tapers  down  to  a  small  point.  The  ulcers 
usually  heal  rapidly.  Simultaneously  with  the  decrease  of  exudate  the 
pulse  becomes  less  frequent,  and,  in  favorable  cases,  maintains  fair 
volume  and  regularity.  The  swelling  of  the  glands  of  the  neck  subsides, 
the  appetite  improves,  and  the  patient  is  fairly  on  the  road  of  con- 
valescence. But  even  when  recovery  seems  most  probable,  the  physician 
in  giving  a  prognosis  should  express  himself  with  some  reservation, 
for  dangerous  symptoms  may  yet  follow,  such  as  indicate  toxaemia, 
heart-failure,  or  paralysis. 

In  very  severe  cases  all  symptoms  are,  of  course,  greatly  intensified, 
and  complications  are  much  more  liable  to  ensue.  The  exudation  is 
usually  copious,  covering  thickly  the  entire  fauces,  and  is  often  seen 
extending  forward  on  the  vault  of  the  mouth  beyond  the  junction  of  the 
soft  and  hard  palates,  on  which  location  it  is  apt  to  be  especially  thick. 

It  frequently  travels  backward  to  the  pharyngeal  wall,  the  postnasal 
space,  and  into  the  nares.  It  may  even  extend  downward  into  the 
larynx  and  trachea. 

As  already  mentioned,  the  local  and  constitutional  symptoms  do  not 
progress  pari  passii.  On  the  contrary,  while  the  exudation  is  increasing 
the  fever  may  diminish  to  such  an  extent  that  the  body  temperature 
is  but  little  above  the  normal.     The  pulse  rate,   however,  does  not 


638  DIPHTHERIA 

always  decrease  proportionately,  but  may  even  grow  more  rapid. 
The  appetite  often  improves,  swallowing  appears  to  be  less  painful,  and 
not  infrequently  the  general  condition  and  strength  of  the  patient  seem 
improved,  while  the  danger  is  in  nowise  diminished.  The  physician 
should  be  careful  not  to  be  misled  by  this  apparent  improvement  while 
the  disease  is  still  progressing. 

When  diphtheria  assumes  the  se'ptic  form,  the  secretion  and  exudation 
of  the  throat  and  nares  undergo  rapid  decomposition,  and,  unless  these 
parts  are  frequently  cleansed  with  antiseptic  washes,  there  is  emitted 
with  the  breath  a  peculiar  odor  which  is  in  the  highest  degree  offensive. 
This  odor  is  often  so  foul  as  to  suggest  the  existence  of  gangrenous 
destruction  of  the  tissues,  and  yet  the  disorganization  of  the  parts  rarely 
amounts  to  more  than  a  superficial  ulceration.  Coincidently  with  this 
condition,  the  cervical  and  submaxillary  glands,  usually  somewhat 
swollen  from  the  beginning,  greatly  increase  in  size  by  inflammatory 
action,  which  also  involves  the  adjacent  cellular  tissue.  While  abscesses 
frequently  form,  yet  it  is  surprising  how  rapidly  this  swelling  will  often 
subside  without  abscess  formation  as  soon  as  the  throat  symptoms  show 
signs  of  improvement. 

In  septic  cases  the  fever,  instead  of  diminishing  in  two  or  three  days, 
as  in  the  other  varieties  of  diphtheria,  continues,  or  may  even  increase, 
until  the  throat  and  nose  symptoms  improve  and  the  swelling  of  the 
neck  subsides.  Recovery  may  take  place  from  this  form  of  the  disease, 
but  the  majority  of  patients  die.  Death  often  occurs  at  an  early  stage, 
as  early  as  the  fifth  to  the  seventh  day,  from  extensive  systemic  poison- 
ing due  to  a  mixed  infection.  Sometimes  the  poisoning  is  more  gradual, 
in  which  case  the  exudate  disappears,  the  glandular  swelling  subsides, 
and  the  temperature  falls,  but  instead  of  improving  the  patient  remains 
apathetic,  loses  weight,  becomes  anaemic,  grows  weaker  and  weaker, 
and  gradually  passes  away.  A  not  uncommon  cause  of  death  is  pneu- 
monia of  septic  origin. 

The  presence  of  epithelial  and  hyaline  casts  in  the  urine,  together 
with  a  large  amount  of  albumin,  points  to  a  rapidly  developing  systemic 
poisoning,  and  may  often  prove  to  be  an  early  monitor  of  danger. 

When  recovery  takes  place  from  the  septic  form  of  diphtheria  con- 
valescence is  usually  very  slow,  often,  indeed,  extending  through  many 
weeks.  The  symptoms  of  septicaemia  become  less  and  less  marked, 
and  prostration  gradually  gives  way  to  general  improvement.  But  in 
the  fourth  or  fifth  week  of  the  disease,  even  after  an  apparent  recovery, 
some  late  complication,  more  especially  general  paralysis,  is  extremely 
liable  to  set  in.  This  is  true  not  only  of  the  septic  form,  but  of  all  well- 
marked  cases  of  diphtheria.  The  vast  majority  of  patients  recover 
from  the  paralysis,  but  it  is  sure  to  prolong  the  period  of  convalescence 
for  weeks  or  even  months. 

In  the  malignant  type  of  diphtheria  the  earliest  symptoms  give 
marked  evidence  of  systemic  poisoning.  By  the  time  the  false  membrane 
has  formed,  which  is  usually  in  twenty-four  to  forty-eight  hours,  the 
whole  organism  is  profoundly  affected.    The  membrane  covers  thickly 


PLATE   LVIII. 


Malignant  Diphtheria. 


Showing  purpuric  discoloration  of  the  face,  ecehynnoses  of  the  eyelids, 
petechia  upon  the  chest,  s-welling  of  the  tongue  and  the  glands  of  the  neck. 
Death  ensued. 


77//';  COUIiHI'],  DUIiATION,  AND  Th'JlM  IN  ATIOS  Oh'  hi  I'll'l  II  l:i{l  A     {]'.\\) 

the  entire  fiuices,  often  involving  \hv  iiares  tilso;  tli(;  hreatli  is  fefifl,  the 
saliva  dribbles  from  the  mouth,  blood  oozes  from  the  nose,  and  pnrj)ijrir 
or  petechial  spots  appear  upon  the  skin;  the  f^lands  of  the  neek  ;irid  the 
periglandular  tissue  are  greatly  swollen;  th(;  face  is  bloated,  pale,  and 
waxy  in  color;  the  tera})erature  is  either  slight ly  elevaterl  or  subnormal; 
the  pulse  may  be  rapid  and  feeble  or  slow  and  irregular,  and  the  intel- 
lect, clear  at  first,  soon  becomes  clouded.  Death  in  these  cases  may 
occur  in  forty-eight  hours,  and  is  rarely  delayed  longer  than  three  or 
four  days. 

The  course  and  duration  of  membra  nous  croup  vary  in  different 
cases,  according  to  the  extent  of  the  disease.  In  mild  cases  the  symp- 
toms often  disappear  in  a  few  days  under  ordinary  treatment,  withf)ut 
operative  interference.  When  the  larynx  is  involved  to  the  extent  of 
causing  stenosis,  death  is  sure  to  result  speedily  if  relief  be  not  afforderl 
If  the  exudation  is  limited  to  the  larynx  the  obstruction  to  respiration 
is  almost  always  overcome  by  intubation,  and  in  the  course  of  six  or 
eight  days  the  patient  may  be  considered  comparatively  free  from 
danger,  at  least  so  far  as  the  primary  trouble  is  concerned.  But  when 
the  exudation  extends  into  the  trachea,  intubation  may  give  relief  at 
first,  though  death  is  liable  to  occur  a  few"  hours  later.  Death  commonly 
results  when  the  disease  extends  into  the  bronchi  and  bronchioles.  It 
occurs  through  insufficient  decarbonization  of  the  blood,  due  to  the 
mechanical  obstruction  caused  by  the  false  membrane  and  retained 
secretions  in  these  parts. 

In  cases  which  linger  longer  the  fatal  result  may  be  brought  on  by 
collapse  of  certain  parts  of  the  lungs  to  which  the  air  does  not  have 
access,  or  by  the  development  of  capillary  bronchitis  or  broncho- 
pneumonia. Many  patients  develop  the  latter  affection  when  they  are 
believed  to  be  well  on  the  way  to  convalescence.  This,  indeed,  is  one 
of  the  principal  causes  of  fatal  termination  in  laryngotracheal  diph- 
theria. 

When  membranous  croup  is  likely  to  terminate  in  recovery,  improve- 
ment begins  with  a  decrease  in  the  fever  and  an  abatement  of  the 
laryngeal  symptoms.  The  false  membrane  usually  disappears  in  from 
four  to  eight  days.  vSomethiies  it  is  coughed  up  in  cylindrical  or  irregular 
casts,  but  more  often  it  disappears  gradually,  probably  by  being  liquefied 
and  expectorated;  it  is  quite  impossible  to  believe  that  it  ever  undergoes 
absorption.  When  throwai  oft'  in  casts  it  is  liable  to  reform,  and  when 
such  new  formations  take  place  the  disease  is  apt  to  terminate  fatally. 
In  patients  that  recover,  hoarseness  or  aphonia,  and  often  some  difficulty 
in  swallowing,  continue  for  a  longer  or  shorter  tune  after  the  intubation 
tube  has  been  removed.  This  change  in  the  voice,  according  to  Oertel, 
is  to  be  ascribed  to  a  flaccid  condition  of  the  vocal  cords  and  atony  of 
the  laryngeal  muscles. 


640  DIPHTHERIA 

RECURRENCE  OF  DIPHTHERIA. 

Many  authors  believe  that  a  second  attack  of  diphtheria  seldom 
occurs  in  the  same  individual  within  a  short  space  of  time.  While  this 
may  be  accepted  as  the  rule,  yet  it  must  be  admitted  that  there  are 
many  exceptions.  It  is  certainly  true  that  a  person  who  has  survived 
the  disease  does  not  have  conferred  upon  him  for  any  considerable 
length  of  time  that  immunity  which  is  so  characteristic  of  scarlet  fever, 
measles,  and  smallpox. 

We  have  quite  often  readmitted  children  to  the  hospital  with  recurrent 
diphtheria  within  a  few  months  from  the  previous  attack;  and  in  two 
or  three  instances,  at  least,  children  have  returned  with  a  third  attack. 
Quite  often  also  have  we  seen  patients  suffer  from  a  relapse  of  the 
disease  before  leaving  the  hospital.  In  such  instances,  after  the  sub- 
sidence of  all  constitutional  symptoms  and  the  complete  disappearance 
of  the  membrane,  the  patient,  during  convalescence,  is  seized  with  a 
sore  throat,  the  temperature  rises,  the  glands  of  the  neck  become  swollen 
and  sensitive,  and  the  exudation  recurs  in  the  throat,  or  nares,  or  both. 

The  relapse  is  not,  as  a  rule,  so  severe  as  the  primary  attack,  but 
there  are  some  exceptions.  We  have  more  than  once  seen  death  result 
from  a  recurrence  of  the  disease. 


COMPLICATIONS  AND  SEQUELS  OF  DIPHTHERIA. 

Heart.^ — The  poison  elaborated  by  the  bacilli  of  diphtheria  is  espe- 
cially prone  to  affect  the  heart.  In  all  severe  cases  heart-failure  is 
extremely  liable  to  occur.  Symptoms  of  this  condition  may  appear 
before  the  pseudomembrane  has  entirely  separated,  but  in  most  cases 
they  are  not  apparent,  or,  at  least,  do  not  become  prominent,  until  the 
characteristic  feature  of  the  local  affection  has,  to  a  great  extent,  dis- 
appeared. In  other  words,  signs  of  cardiac  failure  are  rarely  seen 
until  the  diphtherial  process  has  made  considerable  progress.  They 
do  not  often  appear  before  the  end  of  the  first  week,  but  during  the  four 
or  five  succeeding  weeks  the  patient  is  in  constant  danger  of  heart- 
failure. 

It  is  believed  by  some  authors  that  the  heart  is  affected  to  a  greater 
or  less  degree  in  all  cases  of  diphtheria.  Jacobi^  says:  "There  is  no 
case  ever  so  mild  apparently  that  will  not  affect  the  heart's  function 
at  once  to  a  certain  extent.  From  mild  cases  to  the  gravest  there  are 
gradual  transitions."  In  a  large  proportion  of  the  severe  cases  which 
survive  long  enough  the  myocardium  shows  (post-mortem)  certain 
anatomical  changes,  the  most  common  of  which  is  fatty  degeneration. 

Undoubtedly,  heart-failure  not  infrequently  results  from  paralysis 
of  the  cardiac  nerves,  and  quite  independently,  too,  of  any  anatomical 
change  in  the  heart  muscle.  Lennox  Browne  credits  Vincent,  of  Paris, 
and  P.  Meyer  with  having  found  "widespread  parenchymatous  changes 

1  Twentieth  Century  Practice  of  Medicine. 


COMPrJdATlONS  AND  SI'JQUKLAi:  OF  1)1 1'llTII h'Jil A  fJ41 

in  the  cardiac  plexus  in  two  cases  of  y)afierits  dyin^'  of  }ieart-failure 
during  convalescence  from  dij)hlheria,  in  which  the  heart  muscle  was 
unaffected."  He  says:  "The  changes  were  exactly  similar  to  those 
found   in  the  peri})heral   nerves  in  orflinary  j)ostfli[)}itherific  j)ara]ysis." 

The  symftomn  of  heart-failure  do  not  dilVcr  from  those  of  toxamia. 
Vomiting  is  often  an  early  sign.  The  patient  is  pale  and  sallow,  some- 
times livid  and  cyanotic;  the  pulse  at  first  may  be  rapid  and  feeble, 
but  soon  becomes  slow,  irregular,  and  intermittent,  or  dicrotic.  The 
pulse  rate  is  frequently  as  slow  as  40  to  50  per  minute.  The  first  sound 
of  the  heart  grows  less  distinct.  The  circulation  is  sluggish,  and  the 
extremities  are  cold,  but  the  mind  remains  clear.  In  severe  cases, 
as  the  end  approaches,  the  pulse  becomes  absolutely  lost  at  the  wrist, 
and  death  results  gradually  from  asthenia,  or  it  may  result  suddenly 
from  heart-failure.  Undoubtedly  death  sometimes  occurs  from  paraly- 
sis of  the  cardiac  plexus.  Recovery  but  seldom  takes  place  after  the 
symptoms  of  heart-failure  once  assume  a  threatening  character. 

Lungs. — In  faucial  diphtheria  the  lungs  do  not  very  often  become 
affected.  Bronchitis  occasionally  occurs,  as  does  also  bronchopneumonia. 
But  in  the  laryngotracheal  form  of  the  disease  these  complications  are 
extremely  common.  Indeed,  bronchitis,  more  or  less  marked,  is  not 
very  often  absent  in  membranous  croup.  As  the  inflammation  extends 
downward  from  the  laryngotracheal  surface  to  the  bronchi,  the  inflamed 
mucous  membrane  is  apt  to  become  involved  in  the  diphtherial  process. 
But  quite  apart  from  this,  bronchopneumonia,  catarrhal  in  character, 
is  of  frequent  occurrence,  and  constitutes  one  of  the  principal  sources 
of  danger.  It  most  often  sets  in  before  the  acute  stage  of  membranous 
croup  has  passed,  but  it  may  occur  at  any  period  following  this  stage, 
even  during  convalescence.  J.  Lewis  Smith  says:  "In  121  cases  of 
bronchopneumonia  complicating  diphtheria,  observed  by  Sannp,  the 
pneumonia  commenced  in  2  on  the  first  day  of  diphtheria,  and  in  71 
between  the  second  and  sixth  days  inclusive." 

When  it  develops  at  a  later  stage,  or  during  convalescence,  it  s  in 
most  cases  preceded  by  a  mild  bronchitis  that  has  never  entirely  dis- 
appeared. 

The  existence  of  a  bronchopneumonia  is  revealed  by  physical  exam- 
ination. Both  lungs  may  be  found  involved,  although  the  disease  is 
usually  better  marked  in  one  than  in  the  other.  The  physical  signs 
may  show  that  the  inflammation  is  limited  to  the  lower  lobes,  but  more 
frequently  disseminated  areas  of  inflammation  are  found  throughout 
one  or  both  lungs. 

As  already  stated,  bronchopneumonia  is  one  of  the  chief  sources  of 
danger  in  diphtheritic  croup.  The  mucopurulent  material  secreted  in 
the  bronchial  tubes  may  be  so  abundant  as  to  clog  the  tubes  and  prevent 
proper  decarbonization  of  the  blood.  As  the  inflammation  extends 
to  the  smaller  tubes,  these  often  become  clogged  in  the  same  way  so 
as  to  prevent  the  entrance  of  air  to  the  alveoli,  which  gradually  collapse. 
Autopsies  often  reveal  areas  of  atelectasis  disseminated  throughout  the 
lungs.     Even  where  the  tubes  remain  pervious  it  is  almost  impossible 

41 


G42  DIPHTHERIA 

for  the  child  to  expectorate  the  mucopus  on  account  of  its  viscidity. 
Hence,  the  minuter  tubes  are  usually  found  (post-mortem)  to  be  filled 
with  a  thick,  viscid  material,  containing  also  not  infrequently  floating 
particles  of  pseudomembrane. 

Bronchopneumonia  is  always  attended  by  an  elevation  of  temperature. 
The  disease  may  either  run  an  acute  course,  terminating  in  recovery 
or  death  in  six  to  eight  days,  or  assume  a  subacute  form  and  continue 
to  progress  for  two,  three,  or  more  weeks.  In  some  of  these  persistent 
cases  recovery  finally  takes  place,  but  more  often  death  results  from 
exhaustion.  Bronchopneumonia  is  the  chief  cause  of  death  after 
tracheotomy. 

Lobar  'pneumonia  is  not  a  very  frequent  complication.  It  has  been 
known  to  occur  during  the  stage  of  convalescence.  Areas  of  con- 
solidation in  the  lungs  are  not  infrequently  seen,  but  they  are  almost 
always  associated  with  inflammation  of  the  bronchi. 

Pleurisy  does  not  very  often  occur  as  a  complication.  According  to 
J.  Lewis  Smith,  "Peter  found  the  lesions  of  pleurisy  9  times  in  121 
autopsies  in  diphtheria,  and  Sannd  observed  them  in  20  cases."  The 
latter  is  quoted  as  saying  that  pleurisy  always  accompanies  some  other 
phlegmasia.  In  our  experience  in  the  hospital  we  have  not  seen  more 
than  two  or  three  frank  cases  of  pleurisy  attended  with  pleuritic  effusion. 

Lymphatic  Glands. — Enlargement  of  the  cervical  and  submaxillary 
glands  is  of  common  occurrence  in  diphtheria.  It  may  be  either  slight 
or  excessive.  In  septic  cases  this  complication  is  usually  most  marked. 
As  already  stated,  the  inflamed  glands  sometimes  break  down  into 
abscesses. 

Kidneys. — Renal  complication  occurs  earlier  in  diphtheria  than  in 
scarlet  fever.  Albuminuria  is  frequently  seen  as  early  as  the  third  or 
fourth  day,  sometimes  even  on  the  second,  while  the  quantity  of  urine 
is  not  diminished,  but  may  be  increased.  It  is  believed  that  the  elimi- 
nation of  the  toxin  with  the  urine  irritates  the  kidneys,  and  thus  tends 
to  affect  their  function  or  even  damage  their  parenchymatous  structure. 
In  cases  showing  albuminuria  the  kidneys  may  be  found  to  be  normal, 
or  they  may  exhibit  various  degrees  of  parenchymatous  inflammation. 
While  acute  nephritis  is  not  so  common  as  in  scarlet  fever,  yet  it  does 
occur.  This  is  evident  from  the  fact  that  hyaline  and  granular  casts 
are  sometimes  found.  Red  blood  cells  are  rarely  present.  The  urine 
in  such  cases  is  diminished,  sometimes  scanty,  and  the  skin  becomes 
pallid.  Qildema  is  less  pronounced,  and  ursemic  symptoms  are  much 
less  frequent  than  in  postscarlatinal  nephritis.  Still  patients  die  now 
and  then  from  uraemia.  According  to  Jacobi,  "When  albumose  is 
found,  together  with  considerable  albumin,  Berlin  believes  the  prog- 
nosis to  be  rather  favorable.  Still,  in  most  of  the  cases  at  the  clinic  at 
Strassburg  in  which  he  made  his  observations,  the  renal  complications 
were  only  trifling." 

Park^  says  that  in  most  severe  cases  of  diphtheria  the  kidneys  are  in 

1  Loomis-Thompson,  American  System  of  Practical  Medicine. 


COMPLldATIONH  AND  SI<:QI/ l':/..'l'J  OF  hi I'll'I'll I'.UIA  643 

a  state  of  more  or  less  acute  iiepliril is;  tliat  tliey  an;  usually  hypenemic 
and  enlarged;  that  the  surface  of  the  kidney  is  smooth,  and  frecjuently 
the  seat  of  small  hemorrhages,  and  that,  microscopically,  the  signs  of 
marked  parenchyniatf)us  changes  are  evident  up  to  complete  necrosis 
of  the  epithelium  lining  of  the  tubules.  "In  severe  cases  the  urinr' 
contains  abundant  albumin,  degenerated  kidney  epithelium,  leukocytes 
and  hyaline  casts,  and,  in  the  most  severe,  coarse  and  fine  granular 
casts.    Blood  cells  are  infrequent." 

Lennox  Brow^ne  believes  that  there  is  a  decided  tendency  to  renal 
complications  in  all  cases  intoxicated  with  the  diphtherial  poison.  In 
a  series  of  1000  cases  of  diphtheria  tabulated  by  him  he  found,  however, 
that  the  mortality  due  to  nephritis  and  its  results  was  only  2.7  per  cent. 
This  is  a  much  larger  rate  than  was  observed  in  all  the  Metropolitan 
Asylums'  Board  Hospitals  in  1893,  when,  he  says,  out  of  a  total  of 
2848  cases  of  diphtheria  treated,  with  865  deaths,  only  8  cases  of  neph- 
ritis were  reported.  But  while  actual  nephritis  does  not  occur  with 
great  frequency,  yet,  as  already  stated,  the  parenchymatous  structure 
of  the  kidneys  is  very  commonly  damaged  to  an  extent  that  interferes 
with  their  proper  function.  Lennox  Browne  says  albumin  in  some 
quantity  is  to  be  found  in  the  urine  in  fully  one-half  of  the  cases  of  true 
diphtheria.  Some  other  observers  state  that  it  is  present  even  in  a 
much  larger  proportion  of  cases,  and  believe,  with  Lennox  Browne, 
that  it  is  more  frequently  seen  since  the  serum  treatment  has  been 
employed.  When  it  is  present  to  the  extent  of  more  than  one-eighth 
of  the  volume  of  urine,  the  amount  of  urine  secreted  is  apt  to  be  dimin- 
ished, and  ursemic  symptoms  may  appear. 

As  to  the  frequency  of  albuminuria  in  diphtheria,  J.  Lewis  Smith 
says:  "Bouchut  and  Empis  found  it  in  two-thirds  of  their  cases,  Germain 
S^e  in  one-half  of  his,  and  Sann^  in  224  cases  out  of  410.  In  New 
York  City,  where  diphtheria  has  been  many  years  naturalized  or  endemic, 
I  made,  in  the  years  1875  and  1876,  daily  examinations  of  the  urine 
in  62  consecutive  cases,  and  found  it  present  in  24,  while  38  were  recorded 
exempt.  But  the  proportion  of  cases  as  stated  in  my  statistics  is  probably 
below  the  truth,  for  the  albuminuria  is  sometimes  transient  and  it  often 
occurs  as  a  mere  trace  and  is  liable  to  be  overlooked.  Its  duration  is 
frequently  not  more  than  from  one  to  three  days,  and  in  the  majority 
of  instances  it  does  not  continue  longer  than  ten  days;  but  we  are  all 
familiar  with  cases  in  which  it  continues  fifteen  or  twenty  days,  or 
even  months." 

As  the  amount  of  albumin  in  the  urine  varies  in  different  patients, 
so  also  does  the  day  of  the  disease  on  which  it  makes  its  appearance 
vary.  In  referring  to  Sanne's  observations  on  this  point  J.  Lewis  Smith 
says:  "In  224  cases  albuminuria  was  detected  on  the  first  day  of  diph- 
theria in  3,  on  the  second  day  in  10,  on  the  third  in  30,  on  the  fourth 
day  in  30,  on  the  fifth  day  in  32.  From  the  sixth  day  to  the  eleventh 
the  number  on  each  day  in  whom  albuminuria  was  present  for  the 
first  time  varied  from  10  to  33.  After  the  eleventh  day  there  were  only 
9  new  cases,  and  after  the  fifteenth  day  only  1  new  case.    Hence,  from 


644  DIPHTHERIA 

these  statistics  we  infer  that  there  is  Httle  danger  that  albuminuria  will 
occur  after  the  second  week,  if  the  patient  has  exhibited  no  symptoms 
of  it  previously." 

In  exa.minations  of  the  urine  made  under  our  direction  of  149  diph- 
theria patients  in  the  Municipal  Hospital,  albumin  was  found  to  be 
present  in  85  per  cent,  of  the  cases.  The  cases  were  not  selected,  but 
taken  consecutively  as  they  were  admitted  to  the  hospital  in  two  differ- 
ent periods  of  time.  The  observations,  therefore,  include  both  mild  and 
severe  cases  of  diphtheria.  The  first  series  of  examinations  comprised 
samples  of  urine  from  37  patients,  and  the  second  from  112  patients.  Of 
the  former,  73  per  cent,  of  the  cases  showed  albumin,  and  a  few  showed 
tube  casts  also.  The  urine  was  not  examined  in  all  cases  as  frequently 
as  we  desired,  for  the  reason  that  most  of  the  patients  were  young 
children  from  whom  it  was  often  impossible  to  obtain  specimens.  But 
in  no  case  were  there  less  than  two  examinations,  and  in  some  as  many 
as  twelve.  In  most  of  the  patients  that  recovered  the  urine  became 
normal  during  convalescence,  but  a  few  still  showed  a  trace  of  albumin 
when  discharged  from  the  hospital. 

Of  the  second  series  of  examinations  pertaining  to  the  urine  of  the 
112  patients,  albumin  was  found  in  90  per  cent.;  20  per  cent,  of  these 
cases  showed  albumin  in  large  quantity,  and  70  per  cent,  in  a  less 
amount — not  more  than  a  trace  being  found  in  some. 

In  24  patients  showing  a  large  amount  of  albumin  the  urine  was 
examined  microscopically,  and  tube  casts,  hyaline  and  granular,  were 
found  in  2  of  this  number.  We  should  add  that  1  of  these  patients 
had  nine  months  previously  suffered  from  scarlet  fever,  and  we  had 
no  knowledge  of  the  condition  of  the  urine  since  then. 

Strange  to  say,  in  a  few  of  the  fatal  cases  in  which  the  kidneys  were 
examined  post-mortem  there  was  macroscopic  evidence  of  parenchy- 
matous changes,  although  examination  of  the  urine  had  failed  to  show 
tube  casts  of  any  description. 

Scarlet  Fever. — Scarlet  fever  is  not  an  uncommon  complication  in 
diphtheria;  or,  more  properly  speaking,  one  of  these  diseases  is  often 
found  associated  with  the  other.  We  venture  to  say  that  anyone  who 
has  had  experience  in  a  hospital  for  contagious  diseases  will  bear  out 
this  statement.  Being  familiar  with  the  experience  of,  at  least,  two  or 
three  such  hospitals,  we  know  how  frequently  scarlatinal  rashes  are 
found  in  the  diphtheria  wards,  and,  on  the  other  hand,  how  often 
diphtheria  appears  in  the  scarlet-fever  wards.  For  the  past  two  years 
we  have  been  in  the  habit  of  examining  (bacteriologically)  the  throats 
of  all  scarlet-fever  patients  as  soon  as  they  are  admitted  to  the  hospital. 
In  dividing  these  examinations  into  series  of  100  cases  each,  the 
Klebs-Loeffler  bacillus  has  been  reported  present  by  The  Bacteriological 
Division  of  the  Bureau  of  Health,  Philadelphia,  in  from  10  to  33  per 
cent,  of  the  patients.  Some  showed  well-marked  clinical  evidence  of 
diphtherial  complication,  while  in  others,  it  must  be  said,  such  evidence 
was  not  apparent.  It  is  not  uncommon  to  admit  to  the  hospital  patients 
in  whom  these  diseases  coexist  in  a  well-pronounced  form. 


COMPLICATION H  AND  S/'JtjU l':/..K  OF  1)1 1'll'lll lUilA  f;4rj 

Lennox  Browiic  (jiiolcis  Dr.  \\r\\v.v.  Low  as  sayiiif^  that  "rJuritij^  flie 
prevalence  of  diphtheria  in  Hastings  the  two  diseases  in  certain  instances 
were  concurrent,  and  in  a  number  of  persons  who,  on  account  of  their 
suffering  from  scarlet  fever,  were  sent  to  the  borough  sanatorium  for 
isolation  and  treatment,  were  attacked  by  well-marked  diphtheria 
during  their  convalescence,"  giving  also  several  examj)l(;s  "of  irn[)or(a- 
tion  of  diphtheria  into  families  by  members  returning  home  from  the 
sanatorium  after  recovery  from  scarlatina,  the  patients  in  each  instance 
not  having  been  known  to  suffer  from  diphtheria  during  stay  in  the 
hospital." 

In  many  cases  of  diphtheria  with  concurrent  scarlet  fever  it  is  impos- 
sible to  explain  the  source  of  the  double  infection.  In  hospitals  for 
contagious  diseases  it  is  sometimes  felt  that  one  disease  is  engrafted 
upon  the  other  through  exposure  to  the  second  infection;  but  in  private 
families  these  diseases  not  infrequently  coexist  without  any  known 
or  explicable  cause.  One  of  the  writers  has  just  witnessed  an  instance 
of  this  kind  in  which  two  children  of  a  family  of  three  took  scarlet  fever; 
subsequently  an  infant  of  eleven  months,  who  had  not  been  out  of  the 
house  for  some  time,  fell  ill  with  the  disease  and  in  two  or  three  days 
developed  also  symptoms  of  severe  diphtheria.  Copious  exudate 
appeared  in  the  fauces  and  nares,  and  death  cpiickly  ensued  from 
systemic  poisoning. 

Measles. — The  relation  of  measles  to  diphtheria  is  a  matter  that 
has  not  received  as  much  notice  by  writers  as  its  importance  deserves. 
Ryland  referred  to  it  in  his  Jacksonian  Essay  in  1837,  and  Dr.  West 
in  1843.  A  few  other  observers  have  called  attention  to  the  fact  that 
in  times  of  concurrent  epidemics  of  diphtheria  and  measles,  subjects 
of  the  latter  disease  frequently  suffer  also  from  the  former.  In  reporting 
on  an  outbreak  of  diphtheria  in  1894  at  Barnham  Broom,  England, 
Mr.  T.  W.  Thompson  says:  "I  find  from  my  notes  that  with  one  or  two 
exceptions,  all  the  children,  who  later  suffered  from  diphtheria,  had 
about  this  time  suffered  from  measles,  which  in  some  cases  had  been 
attended  with  considerable  soreness  and  external  swelling  of  the  throat. 
The  frequency  with  which  diphtheria  is  found  to  coexist  with  or  quickly 
follow  in  the  wake  of  measles  is  such  as  to  suggest  a  relationship  between 
the  two  phenomena;  though  the  relationship  may  be  of  an  indirect 
kind  only,  the  measles  increasing  susceptibility  to  diphtheria,  mainly, 
in  all  likelihood,  by  the  damage  inflicted  on  the  mucous  membrane  of 
the  throat."  There  is  no  doubt  that  the  catarrhal  inflammation  of  the 
upper  air  passages  incident  to  measles  affords  a  fertile  soil  for  the 
propagation  of  diphtheria  bacilli. 

The  occurrence  of  measles  with  diphtheria  should  be  regarded  with 
great  apprehension.  The  diphtheria  is  liable  to  assume  the  laryngo- 
tracheal form,  and  the  development  of  bronchopneumonia  is  to  be 
feared.  In  the  year  1900  measles  of  an  unusually  severe  t^'pe  broke 
out  in  the  diphtheria  wards  of  the  INIunicipal  Hospital,  and  in  all  68 
cases  came  under  our  observation.  Of  these  34  died,  making  the 
death  rate  50  per  cent.     Of  the  68  cases,  34  developed  membranous 


646  DIPHTHERIA 

croup,  and  of  these  29  died — a  death  rate  of  85.29  per  cent.  Broncho- 
pneumonia was  the  principal  cause  of  death,  though  some  sank  and 
died  in  a  state  of  adynamia. 

Paralysis. — Paralysis  might  be  regarded  with  much  propriety  as  a 
symptom  of  diphtheria,  but  as  it  is  not  seen  until  the  acute  stage  is 
passed,  and  more  often  during  convalescence,  we  have  preferred  to 
consider  it  as  a  complication  or  sequela.  Very  little  seems  to  have 
been  known  of  diphtherial  paralysis  prior  to  the  latter  part  of  the 
sixteenth  century.  Nicholas  Lepois  called  attention  to  it  in  1580,  and 
Miguel  Heredia  in  1690.  According  to  J.  Lewis  Smith,  Ghisi,  of 
Italy,  in  describing  an  epidemic  which  occurred  in  1747-48,  when  his 
own  son  had  paralysis  in  a  severe  form  following  diphtheria,  says: 
"I  left  to  nature  to  cure  the  strange  consequences,  .  .  .  which 
had  been  remarked  in  many  who  had  already  recovered,  and  which  had 
continued  for  about  a  month  after  recovery  from  the  sore  throat  and 
abscess.  During  this  period  this  child  spoke  through  the  nose,  and 
food,  particularly  that  which  was  least  solid,  returned  through  the  nares 
in  place  of  passing  down  the  gullet."  About  the  same  time  (in  1748) 
Chomel,  of  France,  described  two  cases  of  paralysis  following  what  he 
called  gangrenous  sore  throat.  In  1771,  Dr.  Samuel  Bard,  of  New 
York,  described  the  symptoms  seen  in  a  little  girl  of  two  and  a  half 
years  who  had  recovered  from  "Sore  Throat  Distemper,"  as  follows: 
"Whenever  she  attempted  to  drink  she  was  seized  with  a  fit  of  coughing; 
yet  she  was  able  to  swallow  solid  food  without  any  difficulty.  She 
improved,  but  in  the  second  month  she  could  scarcely  walk  or  raise 
her  voice  above  a  whisper." 

For  the  next  fifty  years  and  more  but  little  is  said  of  diphtheritic 
paralysis.  This  sequel  must  either  have  been  overlooked,  or  regarded 
as  a  coincidence,  or  else  diphtheria  at  that  time  was  of  so  mild  a  type 
that  paralysis  did  not  often  result.  It  appears  that  Bretonneau  had  not 
yet  observed  this  sequela  at  the  time  of  his  first  publication  on  diphtheria 
in  1826.  It  is  said  by  J.  Lewis  Smith^  that  Bretonneau  "did  not  recollect 
that  he  had  seen  a  case  of  diphtheritic  paralysis  prior  to  1843.  Although 
a  close  observer  of  diphtheria,  the  paralysis  had  not  been  observed  by 
him,  or  at  least  had  not  attracted  his  attention,  until  it  occurred  in  the 
person  of  his  townsman.  Dr.  Turpin,  in  1843."  From  this  time  on, 
until  his  second  publication  appeared,  in  1855,  he  saw  a  sufficient 
number  of  cases  to  convince  him  that  this  sequela  occurs  not  infrequently, 
and  called  attention  to  it  in  his  paper  of  the  latter  date.  Since  then 
nearly  every  writer  on  diphtheria  has  described  this  peculiar  form  of 
paralysis,  and  its  frequent  occurrence  is  an  accepted  fact. 

Paralysis  does  not  often  follow  mild  tonsillar  diphtheria.  But  when 
the  soft  palate  and  especially  the  nares  are  involved,  partial  or  complete 
paralysis,  not  only  of  the  muscles  of  the  parts  covered  with  exudate,  but 
also  of  the  entire  muscular  system  is  liable  to  occur. ,  General  paralysis 
does  not  appear  immediately  after  the  local  evidence  of  diphtheria  has 

1  Keating,  Cyclopedia  of  the  Diseases  of  Cliildren. 


aOMI'LICATION^  AND  SFJjlII'.L.K  Ol'    I >l I'll!  II HUI A  047 

disappeared,  hut  (level()]),s  grii(liiiilly  and  slowly.  The  parfs  earliest 
affected  are  the  soft  j)alate  and  fh(;  j)haryiix,  wliile  the  upper  and  lower 
extremities  show  tliis  syni[)toin  later.  From  tlie  slow  development  of 
the  affection  it  seems  probable  that  at  first  only  a  few  fasciculi  are  inca- 
pacitated, and  that  gradually  more  and  more  of  these  become  involved 
until  the  affected  muscles  are  no  longer  under  the  control  of  the  will. 
Paralysis  is  sometimes  ol)served  in  the  muscles  of  the  eyes,  the  trunk, 
the  bladder,  the  rectum,  and  the  diai>hragm.  In  most  cases  the  paralysis 
is  incomplete,  but  in  rare  instances  it  progresses  to  such  an  extent  that 
the  entire  muscular  system  becomes  incapacitated. 

The  cause  and  pathology  of  the  paralyses  are  not  fully  understood. 
It  seems  probable  that  the  condition  is  due  to  a  toxic  neuritis  involving 
the  peripheral  nerves,  causing  an  interruption  of  the  nerve  supply  to 
the  muscles  involved.  It  is  said  that  the  neuritic  change  may  extend 
the  entire  length  of  the  nerves,  from  their  periphery  to  their  origin, 
not  only  of  the  spinal  but  also  of  the  cranial  nerves. 

It  may  be  that  some  of  the  fasciculi  of  the  enervated  muscles  undergo 
fatty  degeneration,  as  this  change  has  been  seen  in  the  myocardium. 
Anatomical  changes  have  been  found  in  the  spinal  cord,  apparently 
resulting  from  myelitis.  S.  G.  Henschrn  has  reported  a  case  of  acute 
disseminated  sclerosis  of  the  cord  with  neuritis.  Some  writers  believe 
that  changes  of  this  nature  contribute  an  important  part  in  the  pro- 
duction of  the  paralysis.  , 

Hemiplegia  is  but  rarely  seen  in  diphtheria.  Only  2  cases  have 
come  under  our  observation.  One  case  has  been  reported  by  J.  W. 
Brannan.  This  writer  is  quoted  by  Jacobi  as  saying:  "There  are  35 
cases  in  all  recorded  in  medical  literature  of  postdiphtheritic  paralysis 
of  cerebral  origin.  Six  cases  have  come  to  autopsy;  in  1  of  these 
a  hemorrhage  was  found  in  the  internal  portion  of  the  lenticular  nucleus, 
with  destruction  of  the  neighboring  part  of  the  internal  capsule.  In 
the  other  5  cases  there  was  embolism  of  the  Sylvian  artery.  .  .  . 
In  the  total  35  cases  there  was  complete  recovery  in  4,  death  in  7;  and 
in  all  the  others  there  was  permanent  paralysis  of  greater  or  less 
extent." 

In  studying  the  causes  of  diphtheritic  paralysis  Trousseau  felt  that 
the  explanation  of  this  symptom  is  beyond  our  comprehension  and 
will  probably  never  be  known.  Realizing  the  insufficiency  of  any  one 
theory  to  explain  all  cases,  Jacobi,  in  his  renowned  treatise  on  diph- 
theria, says:  "It  may  be  positively  asserted  that  diphtheritic  paralysis 
does  not  in  every  case  depend  on  one  and  the  same  cause." 

The  frequency  with  which  paralysis  follows  diphtheria  depends  upon 
the  character  of  the  epidemics.  It  occurs,  of  course,  much  more  fre- 
quently in  severe  attacks  than  in  mild  attacks  of  the  disease.  According 
to  Lennox  Browne,  in  2S48  cases  of  diphtheria  treated  at  the  various 
Metropolitan  Asylums'  Board  Hospitals  of  London,  in  1SP3,  it  was 
noted  in  just  14  per  cent.  This  proportion,  he  says,  agrees  in  the  main 
with  that  deduced  from  his  own  table  of  1000  cases  of  diphtheria. 
While  we  have  no  data  at  hand  of  our  own  experience  on  this  point, 


g48  DIPHTHERIA 

we  believe  that  at  least  14  per  cent,  of  our  patients  developed  paralysis 
more  or  less  marked. 

Since  paralysis  develops  very  gradually  and  slowly,  it  is  not  always 
easy  to  determine  at  which  stage  of  diphtheria  it  begins.  The  difficulty 
is  increased  from  the  fact  that  most  of  the  patients  are  young  children 
in  whom  the  affection  is  usually  not  discovered  until  the  more  char- 
acteristic symptoms  have  appeared.  However,  it  has  been  found  from 
careful  observation  that  paralysis  of  certain  muscles,  the  palatal,  for 
example,  may  occur  in  the  acute  stage,  or,  at  least,  immediately  after 
the  disappearance  of  the  pseudomembrane.  But  the  later  manifesta- 
tions, as  seen  in  muscles  remote  from  the  fauces,  especially  in  those  of 
the  extremities,  diaphragm,  etc.,  are  more  serious,  and  usually  do  not 
appear  in  a  pronour^ced  form  until  after  an  interval  of  more  than  four 
weeks  from  the  commencement  of  the  diphtherial  attack.  We  cannot 
better  illustrate  our  experience  with  this  affection  than  by  quoting 
J.  I^ewis  Smith's  account  of  two  cases  reported  by  Holt:  "A  child,  aged 
two  years,  had  diphtheria  in  August,  and  a  second  attack  in  the  middle 
of  October.  She  convalesced  slowly,  and  in  her  convalescence  had  no 
paralytic  symptoms,  except  a  nasal  voice,  until  December  1st,  when 
multiple  paralysis  suddenly  developed.  A  brother  of  this  patient  also 
had  diphtheria  in  October,  moderately  severe,  and  early  in  convalescence - 
paralysis  of  the  muscles  of  the  palate  began,  followed  by  that  of  the 
other  muscles;  but  it  was  not  until  the  middle  of  December  that  the 
lower  extremities  were  paralyzed."  J.  Lewis  Smith  very  properly  adds: 
''These  cases  are  examples  of  the  usual  mode  of  commencement  and 
extension  of  the  paralysis." 

While  this  sequela  is  not  so  often  seen  after  the  mildest  attacks  of 
diphtheria,  at  least  not  to  any  marked  degree,  yet  instances  have  been 
recorded  in  which  paralysis  has  occurred  in  persons  who,  presumably, 
were  infected  with  the  diphtherial  poisons  without  having  exhibited 
any  of  the  ordinary  symptoms  of  the  disease.  According  to  the  author 
just  quoted.  Dr.  Boissarie^  has  related  cases  of  this  kind  which  are 
remarkable,  if  not  indeed  unique.  He  says  an  officer  of  the  police 
force,  after  ailing  for  two  or  three  days,  had  a  nasal  voice,  and,  in 
attempting  to  drink,  the  liquids  returned  through  the  nose.  The 
velum  palati  was  found  insensible  and  motionless,  but  the  fauces  were 
otherwise  apparently  normal.  "In  the  hospitals  alongside  the  barracks 
in  which  the  above  case  occurred,  a  young  man  without  fever,  redness, 
or  swelling  of  the  fauces,  had  also  a  nasal  voice,  and  return  of  liquid 
food  through  the  nose.  The  porter  of  the  hospital  was  similarly  affected, 
and  the  doctor  stated  that  certain  other  patients  in  like  manner  pre- 
sented symptoms  of  paralysis,  without  the  history  of  an  antecedent 
diphtheria.  Dr.  Reynaud,  called  in  consultation,  expressed  the  opinion 
that  the  paralysis  had  a  diphtheria  origin;  and  this  opinion  was  strength- 
ened by  the  occurrence  immediately  afterward  of  an  epidemic  of  diph- 
theria in  the  place  where  these  cases  occurred."    J.  Lewis  Smith  follows 

1  Gazette  hebdomadaire,  1881. 


COMI'LI(!AT]()NH,  AND  SI<:Q(/I<:LA'J  ()!<'  1)1 1'llTII KIU A  VyW) 

the  account  of  these  unicjue  cases  witfi  the  pertinent  reniark  that  it  is 
probable  an  antecedent  diphtheria  had  occurred  of  so  mild  a  form  as 
to  have  escaped  notice. 

The  paralysis,  as  a  rule,  affects  princijjally  tlie  motor  nerves,  althou^li 
the  sensory  nerves  are  not  infrequently  involved  also.  Anaesthesia  of 
some  parts,  particularly  the  fauces,  has  h)een  observed,  and  tingling 
and  numbness  are  sometimes  felt  in  the  extremities.  The  sense  of 
taste  has  been  known  to  be  affected.  Paralysis  of  the  sensory  nerves 
may  be  quite  local,  and  is  not  seen  until  a  somewhat  later  period  than 
the  motor  paralysis. 

As  the  sympton)s  and  course  of  diphtheritic  paralysis  vary  according 
to  its  location  and  muscles  involved,  it  seems  most  convenient  to  speak 
of  the  clinical  manifestations  of  its  various  forms  separately. 

Paralysis  of  the  palate  is  often  seen  at  an  early  stage  of  the  disease. 
It  may  be  observed  as  soon  as  the  exudate  has  disappeared,  or  as  early 
as  the  tenth  day  of  the  diphtherial  attack.  The  first  evidence  is  mani- 
fested by  a  nasal  tone  of  the  voice.  This  results  from  dropping  of  the  soft 
palate,  causing  the  air  to  escape  through  the  nose  in  the  act  of  speaking. 
There  may  be  slight  difficulty  in  swallowing,  enough  to  make  it  necessary 
for  the  patient  to  drink  cautiously.  Later,  in  the  third  or  fourth  week, 
or  after  convalescence  has  actually  set  in,  the  deglutition  may  become 
more  difficult,  so  that  fluids,  instead  of  being  easily  swallowed,  regur- 
gitate in  large  part  through  the  nares,  while  some  run  down  the 
larynx,  causing  cough  and  sopietimes  pneumonia.  As  already  mentioned , 
anesthesia  is  associated  with  this  form  of  paralysis  and  adds  to  the 
difficulty  of  swallowing.  In  infants  starvation  may  occur  through  their 
inability  to  suckle.  Even  in  older  children,  and  in  adults  also,  when 
general  paralysis  of  an  extreme  form  develops,  deglutition  often  becomes 
impossible,  and  death  from  starvation  may  result  if  feeding  through  an 
oesophageal  tube  be  not  resorted  to. 

When  paralysis  of  the  palate  has  continued  for  a  week  or  two,  faulty 
accommodation  of  the  ocular  movements  may  be  seen.  Most  frequently 
the  paralysis  of  the  ciliary  muscles  is  bilateral.  The  most  common 
variety  of  axis  deviation  met  with  is  convergent  strabismus,  resulting 
from  paralysis  of  the  external  recti  muscles.  Diplopia  is  not  of  infrequent 
occurrence. 

Slight  facial  paralysis  occasionally  occurs.  It  has  been  noted  as 
appearing  soon  after  the  acute  stage.  We  have  seen  but  very  few 
such  cases,  and  in  these  the  affection  was  unilateral. 

Paralysis  of  the  cardiac  and  respiratory  neri'^es  may  appear  any  time 
after  the  first  week  of  the  illness.  The  exudate  may  have  disappeared, 
more  food  is  taken,  the  patient  appears  to  be  gradually  improving, 
and  the  members  of  the  family  are  cheerful  at  the  prospect  of  a  speedy 
recovery,  when  suddenly  the  scene  changes.  The  heart  action  becomes 
weak,  the  pulse  feeble,  slow  and  irregular,  sometimes  rapid,  the  respira- 
tions superficial,  and  the  patient  becomes  pale,  often  slightly  cyanotic. 
Severe  precordial  or  epigastric  pain  is  often  complained  of  in  cases  of 
sudden  heart-failure.     In  the  more  favorable  cases  improvement  may 


650  DIPHTHERIA 

follow  active  stimulation,  and  the  patient  may  eventually  recover.  But 
too  often  the  improvement  is  only  temporary,  for  the  heart-failure  is 
liable  to  return  after  a  few  hours,  or  a  day  or  two  at  the  most,  causing 
sudden  and,  to  the  inexperienced  physician,  unexpected  death.  There 
is  no  other  disease  in  which  symptoms  of  heart-failure  occur  so  suddenly 
and  unexpectedly,  and  there  is  perhaps  no  other  disease  in  which 
physicians  are  so  often  deceived  in  the  matter  of  prognosis. 

Involvement  of  the  respiratory  nerves  leads  to  paralysis  of  the  dia- 
phragm and  sometimes  pulmonary  collapse. 

General  paralysis  does  not  make  its  appearance  until  a  very  late 
stage  of  diphtheria.  It  is  not  often  seen  earlier  than  the  fourth  week, 
and  may  occur  later  than  the  sixth  week.  In  most  cases  it  appears 
between  the  fourth  and  sixth  week.  In  almost  every  instance  it  is 
preceded  by  well-marked  palatal  paralysis,  sometimes  by  loss  of  function 
of  the  muscles  of  the  eye,  especially  those  presiding  over  motion  and 
accommodation.  As  a  rule,  the  loss  of  power  is  first  noticed  in  the 
lower  extremities.  This  may  increase  until  the  limbs,  especially  the 
lower  limbs,  are  rendered  entirely  useless  for  weeks. 

The  comparative  immunity  of  the  fingers  in  many  cases  may  be 
mentioned  as  a  peculiarity.  Parsesthesia  or  anaesthesia,  however,  is 
frequently  noticed  in  the  fingers,  palms  of  the  hands,  and  feet.  The 
degree  of  paralysis  is  not  the  same  in  all  muscles ;  in  some  it  is  complete, 
while  in  others  it  is  only  partial.  When  there  is  complete  loss  of  power 
in  the  lower  extremities  it  is  not  unusual  to  find  that  the  patient  has 
considerable  use  of  the  upper  extremities.  The  muscles  of  the  trunk 
are  often  partially  paralyzed,  but  only  rarely  is  there  loss  of  sensation. 
In  general  paralysis  the  diaphragm  is  often  affected,  but  rarely  to  the 
extent  of  seriously  interfering  with  respiration.  Its  involvement  is  more 
apparent  in  the  act  of  coughing.  In  this  act,  instead  of  the  sudden 
expiratory  explosion,  the  cough  is  slow  and  straining,  and  apparently 
attended  with  some  effort  on  the  part  of  the  patient.  But  paralysis  of 
the  muscles  of  the  pharynx,  preventing  complete  closure  of  the  glottis, 
may  have  more  to  do  in  causing  this  peculiar  symptom  than  paralysis  of 
the  diaphragm. 

As  J.  Lewis  Smith  very  truly  says,  even  where  the  paralysis  seems 
to  be  general  there  are  groups  of  muscles  which  entirely  escape.  He, 
therefore,  prefers  the  term  multiple  paralysis  to  that  of  general  paralysis 
to  designate  this  form  of  the  disease.  . 

Of  the  internal  and  visceral  muscles  liable  to  become  involved, 
paralysis  of  the  diaphragm  or  of  the  heart  is  of  the  most  serious  import, 
as  it  may  be  responsible  for  sudden  death. 

The  bladder  is  sometimes  involved,  but  rarely  to  any  marked  degree. 
We  have  never  found  it  necessary  to  catheterize  a  patient  to  relieve 
this  viscus,  nor  have  we  ever  observed  any  loss  of  power  in  the  sphincter 
muscles.  Paralysis  of  the  muscles  of  the  lower  bowel  and  rectum  is  said 
to  occur  at  times,  giving  rise  to  constipation,  but  not  affecting  the 
sphincters. 

The  ensemble  of  symptoms  of  general  or  multiple  paralysis  is  very 


COMPLICATIONH  AND  HI<:Q(J l<:i.A<:  Oh'  h/ f'lIT// l:UfA  (;ol 

graphically  described  by  Dr.  C.  W.  Fallis  in  the  Medical  Summary, 
January,  ]<S88.  Dr.  Fallis  was  so  unfortunate  as  to  have  suffered 
from  an  attack  of  diphtheria  which  was  followed  by  paralysis.  The 
description  he  ^ives  of  his  own  case  is  as  follows:  "About  three  weeks 
after  the  subsidence  of  the  disease  the  paralytic  syrn[)torns  began  to 
show  themselves.  Impaired  vision  was  the  first  trou})le  noticerl,  inability 
to  accommodate  the  eyes  to  near  objects,  and  in  taking  up  the  paper 
to  read  one  morning  I  found  that  I  could  scarcely  see  a  word,  and  soon 
after,  although  distant  objects  could  l)e  seen  as  well  as  ever,  high-power 
glasses  were  required  to  read  any  kind  of  print.  Double  vision  was 
noticed  afterward.  At  about  the  same  time  numbness  of  the  tongue 
was  felt,  the  muscles  of  deglutition  became  paralyzed,  so  that  swallowing 
was  attended  with  strangling  and  regurgitation  of  food  through  the 
nose.  There  was  a  rapid  pulse,  120  to  the  minute,  showing  that  the 
pneumogastric  was  involved.  Weakness  of  the  limbs,  causing  a  stagger- 
ing gait,  appeared;  fingers  became  weak  and  numb,  so  that  small  objects 
could  not  be  picked  up,  the  symptoms  becoming  worse  and  worse  as 
the  disease  progressed.  The  muscles  of  the  left  side  of  the  face  became 
affected  with  all  the  symptoms  of  facial  paralysis  from  organic  disease. 
Motion  became  more  and  more  impaired,  till  I  could  neither  stand  nor 
walk,  and  when  at  the  worst  I  was  perfectly  helpless,  could  not  feed 
myself,  had  to  be  lifted  from  chair  to  chair,  turned  in  bed,  and  could 
not  even  lift  my  hand  to  my  head,  or  throw  one  limb  over  the  other. 
Sensation  was  so  impaired  that  hands  and  feet  felt  like  lifeless  weights, 
and  in  the  dark  I  could  not  tell  whether  my  feet  were  on  the  floor  or 
not.  The  muscles  of  respiration  were  at  no  time  affected  to  such  an 
extent  as  to  render  breathing  difficult,  and  the  power  of  perfect  speech 
was  retained.  Paralysis  of  the  bowels  necessitated  the  use  of  warm- 
water  injections  to  promote  their  action.  Some  of  the  sjTaptoms  abated, 
while  others  became  more  aggravated,  those  first  to  appear  being  gener- 
ally the  first  to  subside;  however,  the  smaller-sized  muscles  recovered 
rapidly,  while  the  large,  fleshy  ones  were  more  tardy  in  reaching  their 
normal  state,  the  facial  paralysis  lasting  but  a  few  days,  while  loco- 
motion was  either  labored  or  impossible  for  weeks.  The  course  of  the 
disease  from  the  beginning  to  the  worst  stage  was  about  nine  weeks, 
when  it  remained  stationary  for  two  weeks.  Improvement  was  at  first 
very  slow  and  tedious,  but  after  I  could  walk  a  little  it  was  much  more 
rapid,  and  by  the  fifteenth  week,  wath  the  exception  of  some  weakness, 
I  was.  well." 

We  have  seen  many  cases  of  postdiphtheritic  paralysis  presenting 
all  the  symptoms  mentioned  by  Dr.  Fallis.  In  some  of  our  cases  deglu- 
tition was  impossible  for  a  period  of  from  one  week  to  sixteen  days. 
To  sustain  life  through  this  period  it  was  necessary  to  feed  the  patients 
by  means  of  an  oesophageal  tube.  After  the  tube  was  dispensed  with 
swallowing  continued  difficult  for  some  time.  The  vast  majority  of  our 
patients  recovered.  Of  13  cases  observed  by  Cadet  de  Gassicourt, 
6  died. 

Lastly,  tendon  reflex  paralysis  is  very  common.     Indeed,  it  is  said 


652  DIPHTHERIA 

to  be  the  most  frequent  of  all  tb""  paralyses,  probably  occurring  in  one- 
third  to  one-half  of  all  well-marked  cases  of  diphtheria.  Hughlings 
Jackson  called  attention  to  the  fact  that  loss  of  knee-jerk  is  usually  one 
of  the  earliest  symptoms  of  paralysis.  Dr.  R.  L.  McDonnell,  of  Canada, 
believes  it  is  present  in  many  cases  of  diphtheria  from  the  very  first 
day  of  the  illness.  It  is  not  only  the  earliest  of  the  paralytic  symptoms 
to  appear,  but  is  also  of  longest  duration.  In  many  cases  normal 
reflex  only  returns  after  an  interval  of  four  to  six  months. 

The  frequency  of  postdiphtheritic  paralysis  varies  in  different 
seasons,  and,  as  already  stated,  in  different  epidemics.  It  has  been 
found  to  occur  in  from  10  to  30  per  cent,  of  all  cases  of  diphtheria. 
The  affection  is  never  permanent.  Its  duration  is  from  two  to  six 
months,  counting  from  the  time  it  first  appears  until  normal  motion 
is  restored  in  all  muscles. 

Pseudodiphtheria. — ^The  term  pseudo-  or  false  diphtheria  is  now 
commonly  applied  to  an  inflammatory  affection  of  the  throat  character- 
ized by  the  appearance  of  a  peculiar  exudation  in  which  the  Ivlebs- 
Loeffler  bacillus  is  absent.  It  may  occur  primarily  as  a  catarrhal  inflam- 
mation of  the  fauces,  in  which  case  it  is  rarely  severe,  except  when  the 
larynx  is  involved;  or  it  may  occur  secondarily  in  the  course  of  some 
other  affection,  like  scarlet  fever  or  measles,  when  it  is  frequently  fatal. 

While  pseudodiphtheria  is  often  seen  associated  with  scarlet  fever 
or  measles,  yet  it  must  be  remembered  that  true  diphtheria  not  infre- 
quently coexists  with  either  of  these  diseases.  Most  writers  believe 
that  when  pseudodiphtheria  occurs  in  the  course  of  scarlet  fever  or 
measles  it  is  more  liable  to  appear  at  the  height  of  the  primary  disease, 
while  true  diphtheria  more  often  develops  during  convalescence.  Our 
experience  leads  us  to  believe  that  this  is  true  with  reference  to  measles 
only. 

It  is  now  well  known  that  pseudodiphtheria  is  usually  due  to  the 
streptococcus  pyogenes.  This  organism  may  be  found  alone  in  the 
exudation,  but  commonly  the  staphylococcus  aureus  or  albus  is  also 
present.  It  is  said  that  the  staphylococcus  is  occasionally  the  only 
organism  found.  The  condition  of  the  throat  of  persons  suffering  from 
scarlet  fever,  measles,  and  perhaps  some  other  infectious  diseases  is 
favorable  for  the  propagation  of  these  germs.  They  are,  indeed, 
often  found  when  no  exudation  is  present. 

Pseudodiphtheria  sometimes  occurs  as  the  result  of  bad  hygienic 
surroundings,  such  as  imperfect  drainage,  the  inhalation  of  sewer  gas, 
living  in  damp  houses,  and  the  like.  Such  environments  tend  to  render 
individuals  more  susceptible  to  an  inflammatory  affection  of  the  throat 
of  a  membranous  character.  The  streptococcus  organisms  are  so  widely 
distributed  that  pseudodiphtheria  is  liable  to  occur,  not  only  under 
bad  hygienic  surroundings,  but  in  almost  any  place  at  any  time,  pro- 
vided that  the  mucous  membrane  of  the  throat  is  found  vulnerable  to 
an  attack  by  these  organisms.  The  occurrence  of  the  disease  does  not 
depend  upon  exposure  to  a  previous  case,  and  it  rarely  prevails  epidem- 
ically. 


COMPfJdATfONS  AN!)  Sf'JQflMLA'J  OF  1)1 1'llTfl KUJA  053 

\i\  speaking  of  the  roiriTnunicahility  of  p,sciido(]i[>}itheria,  Ifolt  refers 
to  some  important  investigations  made  upon  this  point  by  the  New 
York  Healtli  l^epartment/  He  says:  "As  the  result  of  observations 
upon  450  cases  which  were  followed,  the  cf)nchision  was  reached  that 
the  disease  was  so  slightly  contagious  (if  at  all),  and  usually  so  njild, 
that  strict  isolation  and  subsequent  disinfection  wen;  unnecessary.  Of 
113  cases  occurring  in  100  families,  in  only  14  was  there  a  history  of 
exposure  to  a  similar  case,  and  in  only  9  was  there  another  case  in  the 
same  family.  In  many  of  the  latter  a  common  origin  appeared  more 
probable  than  that  one  case  was  derived  from  another. 

"At  the  present  time  the  general  opinion  of  the  profession  .seems  to 
be  that  these  cases  are  to  a  slight  degree  communicable,  to  be  compared 
in  this  respect  to  ordinary  catarrhal  colds  or  possibly  to  pneumonia. 
They  are  probably  more  contagious  in  the  presence  of  the  poison  of 
scarlet  fever  or  measles." 

For  the  purpose  of  testing  the  communicability  of  p.seudodiphtheria, 
Park^  made  some  very  interesting  experiments  by  inoculating  human 
throats  with  streptococci.  He  describes  the  experiments  as  follows: 
"  A  very  thick  culture  was  made  on  agar  plates  from  a  severe  follicular 
tonsillitis  in  a  young  child,  so  that  there  was  obtained  a  luxuriant 
growth  of  streptococci  growing  both  in  long  and  short  chains,  and  also 
of  other  micrococci.  A  large  amount  of  these  mingled  bacteria  were, 
with  the  permission  of  the  patient,  plastered  on  a  swab  and  then  rubbed 
gently  on  the  right  tonsil  and  into  its  crypts.  He  felt  a  peculiar  sensation 
in  the  tonsil  for  some  twelve  hours;  this  then  passed  away,  and  was 
probably  simply  the  result  of  the  mechanical  irritation. 

"  The  next  morning  the  tonsil  appeared  healthy  except  for  a  small 
patch  in  a  crypt;  from  this,  and  from  the  throat,  cultures  w^ere  made. 
The  plates  gave  very  numerous  colonies  of  streptococci,  w^hile  cultures 
made  from  the  same  regions  the  day  previous  to  the  experiment  gave 
very  few  streptococci. 

"  A  second  trial  was  made  in  a  similar  w^ay  from  a  culture  of  strepto- 
coccus pyogenes,  eighteen  hours  old,  from  a  case  of  extensive  pseudo- 
membrane  and  tonsillar  abscess.  The  results  were  also  entirely  negative, 
except  for  the  increase  of  streptococci  in  the  throat  for  some  days. 
With  the  same  streptococcus  the  tonsils  of  two  other  adults  were  daubed, 
and  with  similar  negative  results. 

"These  trials  having  shown  that  in  three  throats  the  application  of 
streptococci  from  cultures  made  from  virulent  cases  of  tonsillitis  pro- 
duced no  effect,  a  different  experunent  was  tried.  On  two  separate 
occasions  a  sterile  swab  was  rubbed  on  the  tonsils  in  a  case  of  severe 
tonsillitis,  and  then  immediately  rubbed  on  a  healthy  tonsil.  In  neither 
case  was'  there  any  inflammation  excited.  On  the  third  day  after  the 
last  experiment  a  sudden  fall  in  the  temperature  occurred,  and  after 
exposure  a  follicular  tonsillitis  developed,  such  as  frequently  has  followed 
previous  similar  exposures." 

1  Diseases  of  Infaucy  and  Childhood. 

-  Loomis-Thompson,  American  System  of  Practical  Medicine. 


654 


DIPHTHERIA 


These  experiments  seem  to  warrant  the  conclusion,  as  Park  says, 
"  that  the  pyogenic  cocci  are  not  sufficient,  as  a  rule,  to  excite  an  inflam- 
mation in  the  throat."  Or,  in  other  words,  that  the  presence  of  strepto- 
cocci in  the  throat  are  probably  harmless  so  long  as  the  mucous  mem- 
brane is  normal,  or  intact. 

In  primary  cases  the  disease  makes  its  appearance  like  an  ordinary 
sore  throat.  There  may  be  vomiting,  slight  rigors,  headache,  general 
pains,  painful  deglutition,  and  fever.  The  constitutional  symptoms 
are  usually  well  marked  at  the  beginning.  During  the  second  or  third 
day  of  the  disease  the  temperature  may  rise  to  103°  to  104°  F.,  but  it 
quickly  falls  and  the  other  symptoms  also  subside.     On  inspecting  the 


Fig.  97 


A  case  of  pseiKlodiphilifi'ia  iu  lui  adult  negro;  the  exudate  covered  pmuoiis  of  the  hps,  tougue, 
buccal  mucous  membrane,  and  fauces.  Diphtheria  bacilli  were  absent,  but  streptococci  and  staphy- 
lococci were  present. 


throat  the  mucous  membrane  is  found  reddened  and  the  tonsils  swollen. 
Very  soon  an  exudation  appears  upon  the  tonsils,  and  sometimes  upon 
other  parts  of  the  fauces  and  the  buccal  mucous  membrane  also.  The 
exudate  is  grayish  in  color,  shreddy  or  pultaceous,  and  seems  to  lie  upon 
the  surface,  as  it  may  be  readily  removed  with  a  cotton  swab.  It  does 
not  remain  long,  usually  disappearing  in  three  or  four  days.  The  in- 
flammation of  the  throat  is  often  more  marked  than  in  genuine  diph- 
theria, and  swelling  of  the  lymphatic  glands  in  the  neck  may  be  seen, 
though  this  is  not  excessive  in  mild  cases. 

In  many  cases  of  pseudodiphtheria  in  which  the  disease  is  secondary 
to  another  affection  the  symptoms  are  as  mild  as  those  just  described. 


COMPLICATIONS  AND  SICQil HL/K  OF  1)1 1'llTII Klfl A  (\r,r, 

But  frequently  the  local  iri,'uiif(\stati()ii.s  are  as  severe  as  in  the  worst 
forms  of  pharyngeal  (iiphtlK^ria,  and  the  constitutional  syni[)torns  as 
well  marked  as  in  the  septic  form  of  that  disease.  Indeed,  the  clinical 
description  given  of  scarlatina  anginosa  by  some  of  the  older  writers 
is  not  essentially  different  from  that  of  sej)tic  diphtheria,  at  least  so 
far  as  the  greater  part  of  the  local  and  constitutional  symptoms  are 
concerned. 

In  scarlet  fever  the  streptococcic  process  is  liaV)le  to  set  in  at  an 
early  stage  of  the  disease.  In  severe  cases  the  process  may  reach  its 
maximum  in  the  latter  part  of  the  first  week,  and  continue  for  two 
weeks  or  longer.  The  disease  almost  always  involves  the  nose  as  well 
as  the  fauces,  and  very  frequently  extends  to  the  middle  ear,  giving  rise 
to  a  suppurative  otitis  media,  which  may  permanently  affect  the  hearing. 

The  local  process  in  the  throat  is  often  more  destructive  to  the  tissues 
than  is  the  case  in  true  diphtheria.  Deep  sloughing  of  tlie  tonsils  and 
soft  palate  is  sometimes  seen.  The  lymphatic  glands  of  the  neck  and 
the  periglandular  connective  tissue  frequently  inflame  and  break  down 
into  abscesses.  This  process  also  may  be  attended  by  considerable  loss 
of  tissue,  and  occasionally  is  followed  by  serious  hemorrhage. 

When  pseudodiphtheria  occurs  secondary  to  measles  the  throat 
involvement  is  mild  as  compared  with  scarlet  fever,  but  the  strepto- 
coccic process  much  more  frequently  extends  to  the  larynx,  giving  rise 
to  a  dangerous  form  of  membranous  croup.  When  this  condition 
develops  there  is  not  only  danger  from  stenosis,  but  also  from  broncho- 
pneumonia. Sometimes  the  larynx  is  involved  when  there  is  no  sign 
of  exudate  in  the  fauces.  Holt  believes  that  this  is  very  infrequent 
unless  the  disease  is  true  diphtheria;  but  w^e  have  seen  a  number  of 
such  cases  in  which  the  Klebs-Loeffler  bacillus  was  absent. 

In  secondary  cases  the  temperature,  as  a  rule,  ranges  higher  than 
in  the  primary.  The  pulse  rate  is  more  rapid  and  feeble,  and  the 
constitutional  symptoms  as  a  whole  are  severe.  When  the  primary 
disease  is  scarlet  fever,  there  is  usually  restlessness,  delirium,  great 
prostration,  and  albuminuria.  Death  is  liable  to  result  from  septic 
poisoning.  If,  however,  the  patient  withstands  the  toxic  effects  of  the 
streptococcus  organisms,  the  throat  symptoms  improve,  the  constitutional 
disturbance  subsides,  and  recovery  takes  place  as  from  true  diphtheria. 
But  none  of  the  secondary  affections  peculiar  to  the  latter  disease,  such 
as  heart-failure  and  multiple  paralysis,  are  liable  to  follow. 

From  a  clinical  point  of  view  it  is  often  difficult  to  distinguish  between 
pseudo-  and  true  diphtheria.  We  believe  that  in  the  majority  of  cases 
the  experienced  physician  will  make  a  correct  diagnosis  at  the  bedside, 
yet  frequently  one  most  skilled  in  the  art  of  diagnosis  will  find  it 
impossible  to  say,  in  a  given  case,  that  the  pseudomembranous  affection 
of  the  throat  is  not  true  diphtheria.  In  such  cases,  the  assistance 
afforded  by  bacteriology  is  of  great  importance.  Holt  very  truly  remarks : 
"  The  bacteriologists  have  taught  us  to  be  cautious  in  pronouncing  too 
positively  upon  even  the  mild  cases,  as  it  has  been  clearly  shown  that 
some  of  them  may  be  caused  by  the  most  virulent  of  diphtheria  bacilli." 


656  DIPHTHERIA 

Even  in  the  secondary  cases  one  should  not  be  too  ready  to  exclude 
true  diphtheria  in  making  the  diagnosis,  for  it  is  well  known,  as  has 
been  already  pointed  out,  that  this  disease  often  co-exists  with  scarlet 
fever,  and  not  infrequently  follows  in  the  wake  of  measles,  particularly 
when  it  is  prevailing  in  the  neighborhood.  The  clinical  features  dis- 
tinguishing pseudo-  from  true  diphtheria  will  be  considered  later. 

Except  in  rare  instances  of  laryngeal  involvement,  primary  pseudo- 
diphtheria  is  not  a  serious  malady.  Some  mortality,  however,  seems 
to  attend  the  disease,  as  death  rates  varying  from  nil  to  5.5  per  cent, 
have  been  reported  by  different  observers.  According  to  Holt,  of  117 
primary  cases  observed  by  Park  in  the  Willard  Parker  Hospital,  New 
York,  "the  mortality  was  3.5  per  cent.,"  while  ''of  127  cases  of  true 
diphtheria  seen  in  the  same  institution  at  the  same  time,  the  mortality 
was  34.5  per  cent."  Out  of  34  primary  cases  of  pseudodiphtheria, 
which,  in  a  limited  time,  came  under  the  observation  of  Baginsky 
(in  hospital),  the  mortality  was  5.5  per  cent.,  against  38.2  per  cent, 
from  true  diphtheria.  Holt  says :  "  From  the  same  hospital,  Philip  has 
published  a  report  upon  376  cases;  332  of  these  were  true  diphtheria, 
with  a  mortality  of  37  per  cent.;  31  were  cases  of  primary  pseudo- 
diphtheria,  with  no  mortality."  He  also  calls  attention  to  the  fact  that 
"  The  Bulletin  of  the  New  York  Health  Department  contains  a  report 
upon  324  cases  of  pseudodiphtheria  in  children,  with  a  mortality  of 
9,  or  2.8  per  cent.;  4  of  the  fatal  cases  complicated  scarlet  fever;  of  the 
primary  cases,  the  mortality  was  but  1.5  per  cent."  He  adds,  "These 
were  not  hospital  cases." 

During  the  past  ten  years  we  have  observed  in  the  Municipal  Hospital, 
Philadelphia,  172  cases  of  pseudodiphtheria,  with  no  deaths.  All  of 
these  cases  were  sent  in  as  true  diphtheria.  There  was  present  on  the 
tonsils,  rarely  on  other  parts,  a  rather  loose,  filmy  exudate,  which 
disappeared  in  two  or  three  days  after  admission.  Streptococci  and 
other  pyogenic  organisms  were  present,  but  the  Klebs-Loeffler  bacillus 
was  absent.  We  have  not  included  in  this  number  the  cases  of  acute 
follicular  tonsillitis  which  were  also  sent  to  the  hospital  with  the  mis- 
taken diagnosis  of  diphtheria. 

The  mortality  among  the  secondary  cases  of  pseudodiphtheria  is  often 
very  high.  It  is  highest  when  the  disease  occurs  secondary  to  scarlet 
fever  or  measles.  Holt  is  inclined  to  believe  that  under  such  conditions 
it  is  from  20  to  40  per  cent.,  and  that  in  institutions  for  young  children 
it  not  infrequently  reaches  70  or  80  per  cent.,  especially  when  these 
diseases  prevail  epidemically.  He  says  that  under  the  latter  conditions 
"  the  cases  complicating  measles  give,  as  a  rule,  a  higher  mortality  than 
those  complicating  scarlet  fever."  This  statement  accords  with  our 
own  experience. 

As  pseudodiphtheria  is  rarely  communicated  from  one  person  to 
another  the  enforcement  of  stringent  preventive  measures,  such  as 
quarantine  and  disinfection,  does  not  seem  to  be  necessary.  It  is, 
however,  advisable  to  exclude  healthy  children  from  the  sick-chamber. 
In  regard  to  the  secondary  cases,  especially  when  the  primary  disease 


(JOMrLICATIONH  AND  SI'X^I !  HL.K  Oh'  hi  I'll  ■III  i:  HI  A  (;r,7 

was  scarlet  fever  or  measles,  the  c()iii[)li(,'ate(J  cases  slioiihJ  r<rfuiiily  Ijc 
separated  from  the  others. 

Tire  vast  majority  of  j)riina,ry  cases  r(;(|iiire  l)iit  little  treatment,  "^'he 
patient  should  he  ])iit  to  Ix^d  and  giv(^ii  a  li;^li(  diet.  If  the  howels  are 
not  regular  a  mild  cathartic  may  be  administered.  Gargles  are  of 
service  when  the  patient  is  old  enough  to  use  them  prr;pf;rly.  They 
may  consist  of  almost  any  mild  antiseptic  solution.  lioric  acid  in 
the  proportion  of  5  to  10  grains  to  an  ounce  of  water  makes  a  useful 
gargle;  so  also  does  potassium  chlorate  in  solution  (teaspoonful  to  a 
glass  of  water).  Instead  of  using  gargles,  the  throat  may  be  sprayed 
by  means  of  an  atomizer  with  the  boric  acid  solution,  or  with  hydrogen 
dioxide  in  the  proportio;!  of  1  part  to  2  or  8  parts  of  water.  Internally, 
tinctura  ferri  chloridi  in  suitable  doses  will  be  found  serviceable. 

In  the  secondary  cases  closer  watching  is  required,  as  regards  both 
the  local  and  constitutional  symptoms.  If  the  child  is  old  enough, 
more  active  antiseptic  gargles  should  be  used,  such  as  Dobell's  solution, 
perhaps  slightly  diluted,  or  1:5000  or  1:10,000  solution  of  bichloride 
of  mercury,  or  hydrogen  dioxide,  diluted  as  mentioned  above.  The 
gargle  should  be  used  every  hour  or  two  during  the  day,  but  not  quite 
so  often  through  the  night. 

For  accomplishing  the  purposes  of  a  gargle,  the  atomizer  will  often 
be  found  more  convenient  and  satisfactory.  Dobell's  solution,  a  1  or  2 
per  cent,  solution  of  boric  acid,  or  the  hydrogen  dioxide,  will  fre- 
quently give  good  results. 

If  the  nares  be  involved  in  the  streptococcus  process,  as  they  frequently 
are,  the  cavities  should  be  kept  clean  by  frequent  syringing  with  a  bland 
solution,  such  as  the  boric  acid,  or  a  warm  normal  salt  solution. 
The  latter  has  proved  very  serviceable  in  our  hands.  Frequently 
cleansing  the  nose  of  the  mucopurulent  discharge  will  go  very  far 
toward  preventing  middle-ear  disease,  and  even  septic  poisoning. 

Drugs  administered  internally  do  not  influence  the  course  of  the 
disease  to  any  marked  degree.  We  should,  however,  try  to  control 
special  symptoms  as  they  arise.  If  restless,  the  child  should  be  quieted 
with  morphine,  paregoric,  or  chloral  hydrate  guarded  with  a  stimulant. 
Such  drugs  as  the  tincture  of  the  chloride  of  iron,  chlorate  of  potash, 
quinine,  and  strychnine,  are  believed  by  many  practitioners  to  be  of 
service.  Strychnine  or  digitalis  is  indicated  when  the  pulse  is  weak  and 
the  arterial  tension  low.  Above  all,  there  is  nothing  of  greater  impor- 
tance in  the  general  management  of  these  cases  than  stimulation  and 
proper  feeding. 

When  pseudodiphtheria  extends  to  the  larynx,  especially  in  early 
childhood,  intubation  will  probably  be  required.  Inhalation  of  steam 
generated  under  a  croup  tent  will  also  prove  of  great  service,  especially 
when  the  primary  disease  is  measles. 


42 


658 


DIPHTHERIA 


THE  PATHOLOGY  OF    DIPHTHERIA. 

The  most  characteristic  chnical  manifestation  of  diphtheria  is  the 
presence  of  a  pseudomembrane.  This  membrane  may  be  located  in 
various  places  along  the  respiratory  and  upper  digestive  tract.  Lennox 
Browne/  in  a  clinical  study  of  1000  cases,  found  the  membrane  above 
the  larynx  in  841,  or  84.1  per  cent.,  of  the  cases.  The  fauces  and  tonsils 
were  attacked  in  672  cases  and  the  fauces  and  nose  in  165.  The  larynx, 
alone  or  with  the  fauces  and  nose,  was  affected  in  159,  or  15.9  per  cent., 
of  the  cases. 

Holt^  found  the  membrane  above  the  larynx  in  63  cases,  involving  the 
larynx  and  structures  below  in  10  cases,  and  above  and  below  the  larynx 
in  36  cases. 

In  a  careful  study  of  220  fatal  cases  of  diphtheria.  Councilman, 
Mallory,  and  Pearce  found  membrane  at  autopsy  in  127  cases.  It  was 
distributed  as  follows: 


Tonsils  . 

Larynx . 

Trachea 

Pharynx 

Nares    . 

Bronchi 

Soft  palate  and  uvula 

CEsophagus 


65  cases. 

75 

66 

51 

43 

42 

13 

12 


Tongue  . 
stomach 

.  9  cases 
.    5      " 

Duodenum  '  . 

.    1  case. 

Vagina    . 
Vulva     . 

.  2  cases 
.    1  case. 

Skin  of  the  ear 

.    1      " 

Conjunctiva  . 

.    1      " 

The  membrane  varies  greatly  in  appearance;  it  may  be  whitish, 
grayish,  chamois-colored,  yellowish,  brownish,  or  almost  black.  Its 
density  and  consistence  depend  upon  the  amount  of  fibrin  and  other 
constituents.  It  is  at  times  granular,  friable,  and  easily  broken,  and  at 
other  times,  when  the  fibrin  content  is  considerable,  firm,  dense,  and 
elastic.  The  membrane  is  more  closely  adherent  to  the  faucial  and 
laryngeal  mucous  membrane  than  to  that  of  the  lower  respiratory  tract, 
doubtless  owing  to  the  difference  in  the  character  of  the  epithelial  cells. 
There  is,  as  a  rule,  no  diflEiculty  in  detaching  it  from  the  trachea  without 
the  production  of  an  abrasion. 

Histopathology  of  the  Membrane.— The  first  important  contribution 
to  our  knowledge  of  this  subject  was  made  by  E.  Wagner,  who  regarded 
the  membrane  formation  as  due  chiefly  to  a  peculiar  metamorphosis 
of  the  epithelial  cells.  The  cells  degenerate,  fuse,  and  become  converted 
into  a  reticular  membrane.  Cornil  and  Ranvier  confirmed  Wagner's 
observations  and  declared  their  belief  that  the  cells  contained  a  mucin- 
like  substance  and  not  fibrin. 

Weigert  regarded  the  membrane  formation  to  be  the  combined  result 
of  a  coagulation  necrosis  and  a  fibrinous  exudation,  with  the  necrotic 
cells  and  the  fibrin  both  contributing  to  it. 

Peters  was  of  the  opinion  that  the  thick,  dense  diphtheria  membrane 
was  formed  by  a  hyaline  degeneration  of  both  the  epithelial  and 
exudation  cells. 


Diphtheria  and  its  Associates,  London,  1895. 


2  Loc.  cit.,  p.  957. 


Till']  I'ATIIOLOdY  OF  Dll'imi I'Jil .\  05!) 

Orth  (lif1Vreiil,iat(\s  two  (lislirici.  forms  of  striicfurc  in  the  rrifrnhranc: 
one  an  exiulative  inenibraiie  consisting  of  a  fihrin  nieshwork  arifl 
leukocytes,  and  the  other  resulting  from  a  fihriuoifl  degeneration  of 
leukocytes  and  epithelial  cells;  the  latter  is  dense,  elastic,  and  adherf-nf. 
In  addition  to  the  foregoing  writers,  Oertel,  IIeu}>ner,  IJaurngarten, 
Haginsky,  Middcldor])f  and  Gokhiian,  Neunian,  and  others  have 
made  interesting  studies  of  the  diphtheria  membrane. 

Councilman,  Mallory,  and  Pearce  distinguish,  microscopically,  two 
distinct  varieties  of  the  membrane  corresponding  to  the  differences 
observed  macroscopically.  The  dense,  firm,  elastic  membrane  which 
can  be  stripped  off  in  large  flakes  is  composed  of  a  reticular  structure 
with  beams  of  uniform  size.  The  reticulum  contains  masses  consisting 
of  leukocytes  and  epithelial  cells  which  have  undergone  hyaline  degen- 
eration. 

The  other  variety  of  membrane,  which  macroscopically  is  characterized 
by  greater  friability,  is  composed  of  fibrin.  The  fibrin  forms  a  reticulum 
just  as  does  the  hyaline  material,  but  varies  greatly  in  the  size  of  the 
fibres  and  the  spaces.  The  spaces  may  contain  numerous  leukocytes, 
either  well  preserved  or  broken  down. 

The  fibrinous  membrane  is  often  continuous  over  the  entire  surface 
of  the  tonsil  and  extends  into  every  crypt.  The  hyaline  membrane 
never  extends  into  the  crypts,  though  occasionally  small  masses  of 
hyaline  reticulum  are  found  in  them. 

The  changes  in  the  tissues  observed  by  the  above  investigators  are 
summarized  as  follows:  The  first  step  in  the  membrane  formation  is 
degeneration  and  necrosis  of  the  epithelium,  often  preceded  by  active 
proliferation  of  the  nuclei  of  the  cells  by  direct  division.  The  cells  may 
either  break  up  into  detritus  or  become  changed  into  refractive  hyaline 
masses.  An  inflammatory  exudation  rich  in  fibrin  factors  comes  from 
the  tissues  below,  and  fibrin  is  formed  when  this  comes  in  contact  with 
the  necrotic  epithelium.  The  fibrin  in  part  is  formed  into  a  reticulum 
around  exudation  cells  and  degenerated  epithelium ;  in  part  it  combines 
with  the  hyaline  degenerated  cells  to  form  a  hyaline  membrane.  The 
latter  is  most  often  formed  on  those  surfaces  which  are  covered  with 
epithelium  having  several  layers  of  cells.  The  fibrinous  membrane  is 
formed  both  in  the  surface  and  in  the  tissues.  The  membrane  is  never 
formed  primarily  on  an  intact  epithelial  surface,  but  it  may  extend 
over  it.  There  is  nothing  specific  in  the  membrane  formation  in  diph- 
theria, as  typical  hyaline  and  fibrinous  membranes  may  be  found  in 
ovarian  cysts  in  which  bacteria  play  no  part;  but  it  is  accompanied  by 
degenerative  and  exudative  changes  in  the  tissue  beneath. 

The  connective  tissue  and  bloodvessels  undergo  a  hyaline  fibroid 
degeneration.  Necrosis  may  extend  deeply  into  the  tissues,  but  there 
is  little  tendency  to  ulceration  or  abscess  formation.  The  degeneration 
in  the  mucous  glands,  particularly  of  the  glandular  epithelium,  is  so 
pronounced  as  to  be  almost  specific.  The  extent  of  the  necrosis  in  the 
primary  lesions  is  greater  than  is  found  in  the  action  of  any  other 
bacteria. 


G60  DIPHTHERIA 

Diphtheria  bacilli  were  never  found  growing  in  the  hving  tissue  or 
in  connection  with  those  degenerative  changes  in  the  epitheUum  seen 
in  the  beginning.  They  were  found  in  the  necrotic  tissue  and  in  the 
exudation,  usually  only  in  the  latter.  The  bacillus  shows  an  affinity 
for  solid  structures  and  is  found  rather  on  the  reticulum  than  in  the 
spaces  between.  The  beginning  of  the  lesions  is  probably  due  to  the 
toxic  action  of  the  bacilli  possibly  growing  in  the  fluids  of  the  mouth 
or  throat.  When  necrosis  is  once  produced  the  necrotic  tissue  forms 
a  suitable  culture  medium.  The  membrane  and  necrotic  tissue  are 
often  invaded  by  pyogenic  cocci  and  by  fungi. 

Heart. — The  pronounced  clinical  evidence  of  involvement  of  the 
cardiac  muscle  has  led  to  extensive  investigations  of  the  underlying 
pathological  changes  in  the  heart.  This  subject  has  received  careful 
study  on  the  part  of  many  pathologists. 

Hayem  was  the  first  to  call  attention  to  the  granular  and  fatty  degen- 
eration of  the  heart  muscle  and  to  changes  in  the  vessels  and  interstitial 
tissue.  Rosenbach  noted  a  granular  and  waxy  degeneration  of  the 
muscles  and  a  cell  exudation  into  the  interstitial  tissue. 

In  2  cases  of  suddenly  fatal  diphtheria  Birch-Hirschfeld  found 
evidences  of  acute  interstitial  myocarditis.  Martin  regards  the  myo- 
cardial change  to  be  secondary  and  a  result  of  acute  endarteritis  of  the 
coronary  arteries. 

One  of  the  most  important  studies  of  the  heart  in  diphtheria  has  been 
contributed  by  Romberg/  who  made  careful  examinations  in  8  cases. 
He  found  that  the  cardiac  muscle  was  not  uniformly  affected,  but  that 
some  portions  might  be  normal  and  other  areas  show  extensive  changes. 

Small  foci  of  leukocytic  infiltration  were  found  around  the  smaller 
coronary  arteries,  but  the  most  important  lesion  was  the  degeneration 
of  the  cardiac  muscle.  The  degenerated  fibres  had  a  peculiar  vacuola- 
tion  in  the  centre  and  were  without  nuclei.  The  nuclei  undergo  hyper- 
trophy with  an  accompanying  vesicular  condition.  The  inner  and  outer 
portions  of  the  myocardium  showed  most  degeneration. 

Focal  interstitial  changes,  most  common  beneath  the  pericardium, 
were  present  in  all  cases.  In  5  of  Romberg's  cases  pericarditis  was 
present,  and  in  3  there  was  endocarditis. 

Hesse^  made  a  study  of  the  heart  in  29  cases  of  diphtheria.  The 
parenchymatous  changes  were  not  marked  under  three  days,  and  were 
more  pronounced  on  the  left  side.  In  25  out  of  29  cases  interstitial 
myocarditis  was  present,  and  in  4  it  was  marked.  It  was  noticeable 
in  the  first  week,  but  was  more  pronounced  later.  The  interstitial 
changes  were  more  frequent  in  the  left  ventricle.  The  leukocytic 
infiltration  was  believed  to  be  due  to  an  increased  penetrability  of  the 
vessel  walls  which  were  acted  on  by  the  toxin. 

Papkow,  who  examined  a  number  of  hearts  of  patients  who  died  on 
the  third  or  fourth  day,  found  extensive  fragmentation  of  the  muscle 

1  Ueber  die  ErKrankung  des  Herz  mnskels  bei  typhus  abdom.  Scharlach  und  Diphtherie,  Deutsche 
Archiv  f.  kiln.  Med.,  1891,  Bd.  xlviii. 
-  Beitrage  zur  path.  Anatomie  des  Diphtherie  Herzens,  Jahrbuch  f.  Kinderheilk.,  1893,  Bd.  xxxvi. 


Till':  I'ATIIOI/XJY  OF  DII'irrilKKIA  OGl 

fibres,  with  white  and  red  cells  between  th(^  fni^rneiits.  'I'lie  fragmenta- 
tion was  eansed  by  the  swelling  juid  destrneti(;n  of  the  eenient  snl>stanres. 
Tliis  is  an  early  change,  while  tin;  waxy  degenerafion  and  infersfifial 
infiltration  occur  later. 

Welch  and  Flexner  found  fatty  defi;eneration  and  necrosis  of  the 
muscle  fibres,  l^'^lexner  later  described  swelling  and  deeper  staining  of 
the  nuclei,  with  final  disaj)})earance. 

Conncihnan,  Mallory,  and  Pearce  have  made  an  extended  series  of 
careful  examinations  of  the  cardiac  muscle  in  00  cases  of  dij)htheria. 
The  results  of  this  valuable  study  are  herewith  presented :  Fatty  degen- 
eration of  the  muscular  fil)res,  varying  in  extent,  was  found  in  30  of 
the  GO  cases;  there  were  prol)ably  more  than  this  numl)er,  as  only  -^0 
hearts  were  examined  in  the  fresh  state,  and  of  this  number  29  showed 
fatty  change. 

This  degeneration  varies  in  extent,  at  times  affecting  the  myocardinm 
generally,  and  at  times  in  foci.  The  fatty  change  accompanies  and 
appears  to  precede  more  advanced  forms  of  degeneration  which  lead 
to  complete  destruction  of  the  muscle. 

The  sarcous  elements  become  swollen,  broken,  and  converted  into 
hyaline  masses.  Vacuolation,  fragmentation,  and  fracture  of  the  degen- 
erated fibres  are  often  seen.  Simple  fatty  degeneration  is  found  in 
severe  cases  of  short  duration,  and  the  more  extensive  degenerations  in 
protracted  cases.  The  degenerations  are  due  to  the  bacterial  toxin, 
and  account  for  the  impairment  of  the  heart  function. 

Two  kinds  of  interstitial  lesions  are  found.  In  the  one  there  are 
focal  collections  of  plasma  and  lymphoid  cells,  which  may  be  accom- 
panied by  an  independent  myocardial  degeneration,  analogous  to  acute 
interstitial  nephritis.  In  the  other  the  interstitial  change  is  secondary 
to  the  muscle  degeneration.  This  form  may  lead  to  excessive  connective- 
tissue  formation  and  a  fibrous  myocarditis. 

Thrombosis  is  not  infrequently  seen  as  a  result  of  prmiary  necrosis 
of  the  endocardium.  The  only  bloodvessel  change  of  interest  is  pro- 
liferation of  the  intima,  which  is  also  observed  in  other  organs. 

Lungs. — Pulmonary  complications  are  present  in  a  very  large  pro- 
portion of  fatal  cases  of  diphtheria  and  commonly  determine  the  lethal 
outcome. 

The  lesion  found  is  a  bronchopneumonia  of  varying  extent.  Holt^ 
says  that  in  infants  and  young  children  bronchopneumonia  is  found  at 
autopsy  in  at  least  three-quarters  of  the  cases.  Councilman,  ^Mallory, 
and  Pearce  found  bronchopneumonia  in  131  out  of  220  post-mortem 
examinations;  98  of  these  were  in  cases  of  diphtheria  only,  and  33  were 
in  diphtheria  complicated  with  scarlet  fever  or  measles.  The  lung 
complication  was  much  more  frequently  observed  in  patients  in  whom 
the  larynx,  trachea,  and  the  bronchi  were  the  seat  of  membrane.  It 
is  believed  that  the  most  important  factor  in  the  production  of  these 
pneumonias  is  the  aspiration  into  the  lungs  of  micro-organisms,  chiefly 
micrococci. 

1  Loc.  cit. 


662  DIPHTHERIA 

Of  the  131  cases  of  bronchopneumonia,  the  areas  were  discrete  in 
76  and  confluent  in  55.  In  the  majority  of  cases  the  posterior  portion 
of  the  lung  was  affected,  and  especially  the  lower  lobes.  The  bronchi 
were  affected  in  the  majority  of  cases.  The  mucous  membrane  of  the 
large  tubes  was  reddened  and  covered  with  exudation;  drops  of  pus 
could  usually  be  forced  from  the  small  bronchi  by  pressing  the  cut 
surface  of  the  lung. 

In  43  cases  there  was  a  fibrinous  exudation  in  the  bronchi,  forming 
in  the  larger  ones  a  distinct  membrane  and  completely  filling  the 
smaller. 

Councilman,  Mallory,  and  Pearce  conclude  that  there  is  no  organ  in 
which  lesions  accompanying  diphtheritic  infection  are  so  generally  found 
or  so  serious  as  in  the  lung.  In  very  many  cases  they  are  so  extensive 
that  death  may  be  considered  as  due  rather  to  the  condition  of  the 
lungs  than  to  the  throat  affection.  The  essential  lesion  is  broncho- 
pneumonia; true  acute  lobar  pneumonia  was  never  found.  The  cases 
resembling  lobar  pneumonia  were  found  on  close  examination  to  be 
cases  of  extensive  confluent  bronchopneumonia.  The  character  of  the 
exudation  varies;  it  may  be  fibrinous,  hemorrhagic,  serous,  or  almost 
entirely  cellular;  rarely  it  may  be  hyaline.  Atelectasis  is  commonly 
present  in  varying  extent,  and  the  same  is  true  of  emphysema. 

The  cellular  exudate  is  in  part  made  up  of  leukocytes  and  in  part 
derived  from  proliferation  of  the  lining  of  the  membrane.  I^ymphoid  and 
plasma  cells  are  also  found.  In  some  cases  there  is  organization  of  the 
exudation  and  connective-tissue  formation  within  the  air  spaces.  The 
lining  epithelium  of  the  air  vesicles  shows  proliferation.  Necrosis,  in 
some  cases  leading  to  abscess,  is  not  an  uncommon  feature. 

Large  objects  considered  to  be  marrow  cells  which  in  many  cases  have 
undergone  degeneration  are  frequently  found  in  the  capillaries;  it  is 
possible  that  these  have  been  frequently  mistaken  for  hyaline  thrombi. 
Thrombi  are  occasionally  found  in  the  large  vessels,  but  not  in  the 
capillaries.  The  lymphatics  are  commonly  dilated  and  contain  coagu- 
lated albumin,  fibrin,  or  cells.  They  are  often  found  packed  with 
lymphoid  and  plasma  cells,  and  large  cells  similar  to  those  seen  in  the 
air  spaces.  (This  summary  is  based  upon  a  microscopic  study  of  the 
lungs  in  133  cases.) 

Bacteriology  of  Complicating  Bronchopneumonia. — Considerable  dif- 
ference of  opinion  has  existed  as  to  the  comparative  influence  of  the 
diphtheria  bacillli  and  other  organisms  in  the  causation  of  pneumonia 
complicating  diphtheria. 

Thaon,  in  1885,  was  the  first  to  study  the  relation  of  the  diphtheria 
organism  to  secondary  bronchopneumonia.  He  showed  microscopically 
in  the  lung  tissues  the  relation  of  the  bacilli  to  the  inflammatory  process. 
The  diphtheria  bacillus  was  not  found  alone,  but  in  association  with 
various  cocci. 

Loeffler,  iri  his  study  of  the  bacteriology  of  diphtheria  in  1884,  reported 
the  presence  of  the  diphtheria  bacillus  in  the  lung,  but  regarded  it  as 
a  post-mortem  invasion. 


THE  PATUOUMjIY  OF  Dl I'llTII I'UilA  {](])>, 

Various  observers  since  this  time  liav(;  [)iiblis}if'(|  t[i(;  results  of  their 
study  of  tliis  siihjeet.  Tliese  reports  (ixhihit  extretrxily  fhver^erit  firnJings. 
For  instarice,  Wri<fht  and  Stokes  in  ISOf)  found  th(;  dipiitheria  haeilhjs 
in  the  lungs  in  IS  out  of  V.)  eases,  in  8  of  whieii  it  occurred  in  pure 
culture.  On  the  other  hand,  Sims  Woodhead,  in  the  same  year,  found 
the  diphtheria  organism  in  but  5  cases  in  50  autopsies.  Northrup  and 
Prudden  in  1SS9  found  the  diphtheria  bacillus  absent  in  the  lungs 
of  every  one  of  17  cases  examined;  streptococci  were  present  in  all,  and 
staphylococci  in  13  cases. 

In  a  series  of  88  cases  of  diphtheria  in  which  cultures  were  made 
from  the  lungs  by  Councilman,  Mallory,  and  Pearce,  the  diphtheria 
bacillus  was  found  in  49  cases,  in  15  of  which  it  appeared  in  pure  culture. 
The  streptococcus  was  present  in  51  cases,  in  15  of  which  it  was  found 
alone.  The  staphylococcus  aureus  was  noted  in  27  cases,  and  the 
pneumococcus  in  10. 

These  writers  conclude  that,  "  contrary  to  the  results  obtained  from 
cultures,  the  pneumococcus  must  be  considered  the  principal  agent  in 
producing  the  lung  affection.  The  diphtheria  bacilli  are  frequently 
found  and  may  be  the  cause  of  bronchitis  with  membrane  formation, 
of  purulent  exudation,  of  bronchopneumonia,  necrosis,  and  abscess. 
They  are  often  found  in  the  lung  in  much  greater  numbers  than  in  any 
other  situation,  and  there  may  be  but  little  change  in  the  tissue  around 
them." 

It  should  be  stated  that  Councilman,  Mallory,  and  Pearce  found  the 
pneumococcus  59  times  in  microscopic  sections  and  11  times  in  cultures 
made  from  the  same  cases.  Diphtheria  bacilli  were  found  60  times  in 
cultures  and  38  times  in  sections;  streptococci  53  times  in  cultures  and 
29  times  in  sections. 

Flexner  inoculated  the  trachea  of  rabbits  with  diphtheria  bacilli  and 
induced  /pneumonia  in  a  short  time.  He  believed  the  infection  to  be 
produced  directly  and  also  through  the  blood  and  lymph  channels. 

Pleural  Membranes. — Councilman,  Mallory,  and  Pearce  stated  that 
in  18  cases  there  was  pleurisy  with  fibrinous  exudation,  1  with  sero- 
fibrinous exudation,  in  7  empyema,  in  1  pyopneumothorax,  and  in 
1  hemorrhage  into  the  pleural  cavity.  Small  pleural  ecch}Tnoses, 
irregular  in  shape,  were  found  frequently,  chiefly  over  the  surface  of 
the  lower  and  posterior  lobes. 

Spleen. — The  changes  in  the  spleen  in  diphtheria  have  been  studied 
by  Bizzozero,  Oertel,  Miiller,  Katzenstein,  Ziegler,  Ribbert,  "Waschke- 
witch.  Babes,  Flexner,  and  Councilman,  Mallory,  and  Pearce,  by  whom 
the  above  writers  are  mentioned.  INIost  of  these  observers  describe,  as 
the  salient  features  of  the  alterations  in  the  spleen,  the  presence  of  large, 
phagocytic,  epithelioid  cells  in  the  lymph  nodules  and  a  necrosis  of  the 
lymphoid  cells. 

Flexner  found  the  lesions  in  the  splenic  Ipnph  nodules  similar  to  those 
in  lymph  nodes,  save  that  in  the  former  the  nuclear  fragments  were  not 
so  often  seen  in  phagocytic  cells.  The  pulp  exhibited  hyperplasia  of 
the  reticular  and  vascular  endothelia,  with  nuclear  destruction  of  the 


664  DIPHTHERIA 

cells,  both  within  and  without  the  vessels.  Waschkewitch  examined  the 
spleen  of  diphtheria  and  other  patients  in  a  large  number  of  cases. 
Large  epithelioid  cells  were  observed  in  21  out  of  24  cases  of  diphtheria, 
and  in  11  out  of  170  other  spleens  exainined.  He  believes  that  these 
cells  are  not  characteristic  of  diphtheria,  but  may  be  found  quite  often 
in  children  dying  of  other  diseases. 

Councilman,  Mallory,  and  Pearce  state  that  there  is  but  little  change 
in  the  gross  appearance  of  the  spleen;  it  is  generally  firm,  not  distended, 
with  smooth  capsule.  As  a  rule  the  lymph  nodules  are  distinctly  visible 
on  section,  and  at  times  very  prominent.  The  size  of  the  organ  varies, 
but  usually  within  normal  limits.  The  spleen  was  examined  microscop- 
ically in  181  cases,  from  the  second  to  the  one  hundred  and  eighth  day 
of  the  disease,  and  in  subjects  from  ten  months  to  sixty  years  of  age. 
Most  of  the  specimens  examined  were  from  patients  under  four  years 
of  age  and  under  ten  days'  duration  of  the  disease.  The  most  con- 
spicuous change  in  the  lymph  nodules  was  the  formation  of  small  areas 
composed  of  epithelioid  cells  of  hyaline  material  and  of  a  variable 
amount  of  nuclear  detritus.  This  varied  according  to  the  duration  of 
the  disease. 

The  epithelioid  formation  usually  occurred  early  and  the  hyaline 
change  late.  Such  areas  were  found  in  91  of  181  cases  examined.  The 
epithelioid  cells  were  large,  with  variously  shaped  vesicular  nuclei,  and 
finely  granular  protoplasm ;  they  resembled  the  epithelioid  cells  found 
in  tubercle.  They  were  formed  in  the  same  way  as  those  seen  in  the 
lymph  nodes.  The  epithelioid  cells  are  phagocytic  and  contain  a 
nuclear  detritus  which  is  derived  from  the  contained  lymphoid  cells. 

In  17  of  the  181  cases  there  was  well-marked  degeneration  of  the 
arteries  in  the  lymph  nodules.  The  process  was  limited  to  the  arteries 
in  the  lymph  nodules.  There  was  hyaline  degeneration  of  the  entire 
vessel  wall  in  many  cases,  with  the  hyaline  extending  from  the  vessel 
into  the  tissue.  The  lumen  of  the  vessel  was  narrowed  and  in  some 
cases  almost  obliterated.  This  condition  was  most  pronounced  in  the 
acute  cases. 

Changes  in  the  veins  similar  to  those  described  by  Pearce  in  scarlet 
fever  were  found  in  12  cases.  These  consisted  chiefly  of  an  accumula- 
tion of  lymphoid  and  plasma  cells  beneath  the  epithelium  of  the  intima. 

Plasma  cells  were  found  in  the  spleen  in  large  number  in  the  later 
stages ;  this  suggests  that  this  organ  may  play  an  important  role  in  their 
formation.     No  bacteria  were  found  in  the  sections. 

Alimentary  Canal. — In  1888  Smirnow  published  a  report  of  6  cases 
of  pharyngeal  diphtheria  in  which  distinct  membrane  was  found  in  the 
stomach.  The  membrane  resulted  from  an  inflammatory,  fibrinous 
exudation  in  3  cases,  and  in  the  other  3  it  was  due  to  a  hyaline  degen- 
eration of  the  granular  and  surface  epithelium. 

Cronemeyer,  in  an  analysis  of  459  cases  of  diphtheria,  mentions  29 
cases  of  diphtheria  of  the  stomach. 

Councilman,  Mallory,  and  Pearce  found  5  cases  among  220  autopsies 
in  which  a  definite  diphtheritic  membrane  was  present  in  the  stomach. 


Tiii<:  I'ATiioLoay  of  dii'II'iiiI'Ihia  OOfj 

Til  one  case  almost  tlie  entire  surface  of  the  ^aslric  iniieosa  was  eovered 
with  a  thi(;k,  ragged,  (rrayisli-hrown  membrane,  wliicli,  on  removal,  left 
a  red,  granular  surface  beneath.  In  the  other  eases  the  formation  of  the 
membrane  was  not  extensive,  and  was  limited  to  lines  on  the  surface  of 
the  rugfE.  Various  bacteria  were  found  in  the  membrane,  but  tliere 
were  very  few  diplitheria  bacilli.  Upon  culture,  however,  abnndanf 
bacilli  were  found  in  these  cases. 

The  intestinal  mucous  membrane  showed  but  few  gross  changes.  It 
varied  considerably  in  thickness,  in  some  cases  being  decirledly  atrf)phic. 
The  most  marked  change  was  the  hyperplasia  of  the  lym})hoid  struc- 
tures. Pcyer's  patches  were  in  some  cases  so  swollen  as  to  resemble 
those  seen  in  the  early  stage  of  typhoid  fever.  The  swelMng  was  rarely 
homogeneous,  but  the  single  lymph  nodules  or  groups  of  them  could 
be  distinguished,  forming  round  or  elongated  elevations  with  pits  or 
furrows  between  them.  The  solitary  lym])h  glands  in  both  large  and 
small  intestines  stood  out  prominently.  I\Iicr()scoj)ic  examinations  were 
made  in  GO  cases.  The  changes  in  the  intestinal  lymph  nodules  were 
identical  with  but  less  pronounced  than  those  in  the  lymph  nodes 
generally.  There  was  marked  hyperplasia,  and  in  20  cases  focal  lesions, 
such  as  are  seen  in  the  spleen  and  lymph  nodes.  The  vascular  endo- 
thelium was  swollen  and  proliferated,  and  often  contained  lymphoid 
cells. 

Bizzozero  and  Oertel  found  similar  alterations  to  those  here  described . 

Welch  and  Flexner,  in  experimental  diphtheria,  found  in  addition  to 
necrosis  in  the  lymph  nodules  a  general  diffuse  necrosis  affecting  the 
glandular  epithelium. 

Courmont,  Dogan  and  Paviot  injected  dogs  with  diphtheria  toxin  and 
produced  hypera?mia  and  degeneration  of  Peyer's  patches. 

The  changes  above  described  are  probably  due  to  the  action  of 
toxins,  absorbed  not  from  the  alimentary  canal,  but  from  the  blood 
current. 

Liver. — Oertel  was  one  of  the  first  observers  to  study  the  microscopic 
changes  in  the  liver  in  diphtheria.  He  found  small  hemorrhages  beneath 
the  peritoneum  and  in  the  more  superficial  parts  of  the  liver  substance. 
He  also  noted  a  leukocytic  infiltration  of  the  subperitoneal  and  peri- 
portal connective  tissue,  with  a  fatty  degeneration  of  the  liver  cells  in 
the  neighborhood  of  the  cell  invasion. 

Katzenstein  observed  cloudy  swelling  and  fatty  degeneration  of  the 
liver  cells,  exudation  of  leukocytes  in  the  periportal  connective  tissue, 
nuclear  degeneration,  and  in  a  few  cases  hyaline  degeneration  of  the 
walls  of  the  capillaries. 

Gaston,  in  a  study  of  the  hepatic  changes  in  various  infectious  pro- 
cesses, described  in  diphtheria  congestion  of  the  vessels,  fatty  degen- 
eration of  liver  cells,  particularly  in  the  centre  of  the  lobules,  and 
embryonic  cell  infiltration  of  the  periportal  spaces. 

Barbacci  found  abundant  leukocytes  in  the  hepatic  vessels,  swelling 
of  the  capillary  epithelium,  and  hyaline  degeneration  of  the  walls.  The 
liver  cells  were  granular,  swollen  and  oedematous,  and  showed  various 


QQQ  DIPHTHERIA 

degenerative  changes.  The  leukocytic  infiltration  of  the  periportal 
connective  tissue  was  almost  constant. 

Babes  found,  in  diphtheria  produced  experimentally  in  animals,  the 
liver  cells  swollen,  pale,  granular,  and,  in  places,  filled  with  fat.  In 
addition  there  were  areas  of  leukocytic  infiltration  and  swelling  of  the 
endothelial  lining  of  the  bloodvessels. 

Welch  and  Flexner  have  thoroughly  studied  the  hepatic  changes  in 
experimentally  induced  diphtheria.  The  most  important  changes  were 
necrosis  of  liver  cells,  affecting  chiefly  definite  groups  of  cells,  leukocytic 
infiltration  in  the  necrotic  foci,  and  swelling  and  proliferation  of  the 
endothelial  cells  of  the  capillaries. 

Baldassari  found  cloudy  swelling,  fatty  degeneration  and  necrosis  of 
liver  cells,  and  fragmentation  of  the  chromatin  network  of  the  nuclei. 

Councilman,  Mallory,  and  Pearce  examined  the  liver  in  180  cases  of 
diphtheria.  There  were  no  characteristic  gross  appearances.  It  was 
generally  slightly  swollen  and  somewhat  tense  and  congested.  In  some 
cases  the  congestion  was  pronounced,  but  in  others  the  liver  was  pale 
and  cloudy,  due  largely  to  fatty  degeneration. 

Microscopically,  the  most  constant  lesion  was  swelling  of  the  cells  with 
increased' granulation;  this  was  most  marked  in  the  centre  of  the 
lobules. 

In  place  of  the  fine,  even  granulation  of  the  normal  cell,  coarse 
granules  of  irregular  size  appear. 

It  was  difficult  to  judge  of  the  presence  and  degree  of  fatty  degen- 
eration. Many  of  the  liver  cells  contained  fat-vacuoles.  The  most 
extensive  fatty  degeneration  consisted  of  an  actual  necrosis  of  the  liver 
cells.  The  necrosis  was  most  marked  about  the  hepatic  veins  and  was 
always  found  affecting  groups  of  cells.  In  most  cases  the  necrosis  is 
confined  to  the  centres  of  scattered  lobules;  in  others  almost  all  the 
lobules  in  the  section  are  affected.  The  disseminated  foci  were  not  so 
common  as  the  central  necrosis;  they  were  found  in  but  7  of  the  180 
cases,  whereas  the  central  necroses  were  found  in  22.  The  two  processes 
were  but  rarely  associated. 

Flexner  regards  the  necrosis  in  experimental  diphtheria  as  due  to 
injury  of  the  vessel  wall  at  some  point,  allowing  transudation  to  take 
place  more  freely.  He  believes  the  injury  is  produced  at  some  period  of 
greater  concentration  of  the  toxin  and  at  a  point  where  the  circulation 
is  slowed  or  at  a  standstill. 

In  addition  to  the  changes  above  mentioned  there  is  occasionally  seen 
a  slight  hyaline  degeneration  of  the  capillary  walls;  the  capillaries  con- 
stantly contain  an  increased  number  of  cells  which  are  derived  in  part 
from  proliferation  of  the  endothelium,  and  in  part  from  cell  infiltration. 

The  lesions  in  the  liver  in  diphtheria  are  not  characteristic  of  the 
disease;  similar  changes  are  found  in  other  infectious  processes.  No 
diphtheria  bacilli  were  found  in  the  microscopic  sections.  The  hepatic 
lesions  in  human  diphtheria  differ  from  those  experimentally  induced 
in  animals,  chiefly  in  the  greater  frequency  of  the  central  situation  of 
the  necroses. 


77//';  rATiiOLOdV  Oh'  i)ii'ii'riii<:iiiA  (;f;7 

Kidneys. — The  pathological  changes  in  the  kirlneys  in  fli|>ht}ifria 
liave  l)een  studied  i)y  Branlt,  Fiirhrinf^er,  l^'i.s(;hl,  Cjcrtel,  iiernard  and 
Felsenthal,  Reiehe,  Katzenstein,  and  others.  The  alterations  iriflueed  by 
experimental  diphtheria  have  been  specially  described  l;y  Flexner. 

Councilman,  Mallory,  and  Pearce  examined  the  kidneys  micro- 
scopically in  171  cases.  The  ages  of  the  patients  varierl  from  two 
months  to  thirty  years,  and  averaged  three  and  three-quarter  years. 
It  v^as  found  possible  to  divide  the  kidneys  into  five  classes  according 
to  the  microscopic  findings:  1.  Those  in  which  degeneration  of  the 
epithelium  was  the  chief  or  the  only  lesion.  2.  Those  in  which  acute 
interstitial  changes  consisting  of  cell  accumulations  in  the  vessels  and 
interstitial  tissue  were  present.  3.  Those  in  which  the  chief  lesions  were 
found  in  the  glomeruli.  4.  Those  in  which  hemorrhages  into  the 
tubules  were  present.  5.  Those  in  which  chronic  interstitial  lesions 
were  present  as  shown  by  atrophied  glomeruli  and  increase  in  the 
connective  tissue. 

1.  Degenerative  Changes. — Degenerative  changes  of  varying  grades 
were  found  in  112  of  the  171  cases  examined.  Many  kidneys,  almost 
or  quite  normal  in  appearance,  showed  under  the  microscope  a  con- 
siderable degree  of  degeneration.  The  degeneration  was  slight  in  26 
cases,  moderate  in  38,  marked  in  37,  and  extreme  in  9  cases.  The 
most  extreme  degree  was  found  in  severe  cases  dying  shortly  after  entry 
into  the  hospital. 

Fatty  degeneration,  as  determined  by  examination  of  frozen  sections, 
was  only  slight  in  degree;  it  occurred  in  44  out  of  58  cases  examined  in 
this  manner. 

Some  degree  of  hyaUne  degeneration  w^as  found  in  almost  all  the  cases, 
affecting  prominently  the  proximal  convoluted  tubules.  Casts  w^ere 
present  in  practically  all  of  the  cases,  especially  when  the  hyaline 
degeneration  was  pronounced. 

The  most  constant  change  seen  in  the  glomeruli  consisted  of  a  small 
amount  of  granular  coagulum  between  the  tuft  and  the  wall. 

In  40  cases  of  simple  degeneration  the  urinary  record  is  available. 
Albumin  was  found  in  33  of  the  cases.  There  was,  with  some  excep- 
tions, a  general  agreement  between  the  presence  of  albumin  and  the 
degree  of  degeneration. 

There  appeared  to  be  no  relation  between  the  character  of  the  degen- 
eration and  general  infection  with  various  bacteria.  In  the  110  cases  a 
general  infection  with  diphtheria  bacilli  was  noted  in  20  cases,  with  the 
streptococcus  in  29  cases,  with  the  staphylococcus  aureus  in  4  cases,  and 
with  the  pneumococcus  in  3  cases.  In  the  9  cases  of  severe  degeneration 
general  infection  was  noted  but  once,  and  that  with  the  streptococcus. 

2.  Acute  Interstitial  Changes. — iVcute  interstitial  nephritis,  evidenced 
by  infiltration  of  the  interstitial  tissue  with  cells  of  the  plasma  t^•pe, 
was  present  in  43  of  the  cases.  The  kidneys  were  but  slightly,  if  at  all, 
enlarged,  save  in  the  most  marked  cases,  when  considerable  swelling 
was  present.  The  interstitial  infiltration  was  general  in  all  parts  of 
the  kidney,  but  was  more  intense  in  foci;  most  of  the  cells  were  plasma 


668  DIPHTHERIA 

cells  with  typical  nucleus  and  protoplasm.  Lymphoid  cells  and,  in 
severe  cases,  large  phagocytic  cells  were  also  present.  The  amount  of 
epithelial  degeneration  varied  in  different  cases. 

The  infiltrating  cells  were  usually  limited  to  the  interstitial  tissue; 
the  changes  we.re  accompanied  by  alterations  in  the  vessels,  the  cell 
infiltration  at  times  almost  obscuring  them.  The  degeneration  found 
in  foci  of  intense  infiltration  appears  to  depend  on  malnutrition  resulting 
from  blocking  of  the  vessels  by  the  cells. 

In  all  of  the  interstitial  cases  the  duration  of  the  disease  was  more 
prolonged  than  in  the  cases  of  simple  degeneration.  The  average 
duration  of  the  illness  was  twenty-one  and  one-half  days.  The  inter- 
stitial process  apparently  takes  some  time  for  its  development,  and 
the  cases  dying  early  do  not,  as  a  rule,  show  the  process  at  its  maximum. 
Mixed  infections  with  scarlet  fever  and  measles  are  more  apt  to  cause 
interstitial  changes  than  simple  degeneration.  The  urine  was  tested 
for  albumin  in  15  cases,  in  14  of  which  it  was  found  present. 

3.  Glomerular  Changes.^ — This  variety  of  the  disease  was  found  in 
11  cases,  in  all  of  which  the  glomerular  changes  were  the  predominating 
ones.  Lesions  of  the  glomeruli  were  uncommon  in  the  cases  of  simple 
degeneration  and  in  those  showing  interstitial  involvement. 

The  first  evidence  of  change  in  the  glomeruli  is  increase  in  the  number 
of  cells.  The  endothelial  lining  of  the  vessels  undergoes  proliferation 
and  occludes  the  vessel.  Later  a  hyaline  degeneration  of  the  cells  and 
the  vessel  walls  takes  place. 

Glomerular  nephritis  was  present  in  subjects  averaging  a  greater  age 
than  the  degeneration  and  interstitial  cases.  The  average  duration  of 
the  disease  at  the  time  of  autopsy  was  also  greater. 

4.  Hemorrhage. — Slight  hemorrhages  in  the  kidney  were  seen  in  3 
cases,  but  true  hemorrhagic  nephritis  was  noted  in  but  1.  The  red 
blood  cells  were  found  chiefly  in  the  tubules  and  the  interstitial  tissue. 
The  rarity  of  hemorrhagic  cases  was  considered  surprising. 

5.  Chronic  Cases. — In  4  cases  chronic  changes  were  present,  as 
evidenced  by  atrophy  of  the  tubules  and  increase  in  connective  tissue. 
In  these  cases  death  occurred  at  entirely  too  early  a  date  to  attribute 
the  changes  to  diphtheria;  the  lesions  were  evidently  due  to  some  ante- 
cedent disease. 

Councilman,  Mallory,  and  Pearce  conclude  that  lesions  of  the  kidney, 
varying  from  simple  degeneration  to  the  more  serious  conditions  of  acute 
nephritis,  are  found  in  all  fatal  cases  of  diphtheria;  there  is,  however, 
no  type  of  lesion  peculiar  to  the  disease. 

Lymph  Nodes. — The  changes  in  the  lymph  glands  have  been  studied 
by  Bizzozero,  Oertel,  Bullock  and  Schmorl,  Barbacci,  Bezancon  and 
Labbe,  Flexner,  and  Councilman,  Mallory,  and  Pearce.  The  most 
constant  changes  observed  by  these  investigators  have  been  a  marked 
cellular  infiltration  and  the  presence  of  necrosis.  Bullock  and  Schmorl 
found  diphtheria  bacilli  in  the  nodes  in  11  out  of  14  cases. 

Councilman,  Mallory,  and  Pearce  examined  the  lymph  nodes  in  109 
cases.    They  were  constantly  the  seat  of  pathological  changes. 


Tim  PATIIOLOCV  01''  DII'II'IIIFJUA  GOD 

Tlie  nodes  iiiosl.  involved  are  tliose  neuresl,  l,o  the  seat  of  exudate  - 
the  tonsils  aixl  the  cervical  {glands.  The  distant  nodes  are  very  rarely 
aH'ected. 

The  lesions  are  most  prononnced  in  severe  cases,  in  vviiich  a  fatal 
termination  occnrs  early.    Two  varieties  of  lesions  are  descril)ed : 

1.  The  ordinary  lesions,  which  may  follow  an  injnry  of  almost  any 
sort  and  wliicli  consist  in  congestion,  hemorrhage,  and  diffuse  and 
circumscribed  necrosis.  Numerous  new  cells  are  found  which  are 
derived  partly  from  the  lymphoid  cells,  and  partly  from  proliferation  of 
the  endothelial  cells  of  the  sinuses  and  reticulum.  The  swelling  of  the 
nodes  is  due  chiefly  to  congestion,  hemorrhage,  and  dilatation  of  the 
sinuses;  the  lymphoid  cells  do  not  increase  perceptibly  in  number. 

2.  Lesions  which  are  distinctive  of  diphtheria,  but  which  may  be 
found  in  other  infectious  diseases  in  children.  Foci  are  formed  which 
are  similar  in  appearance  to  miliary  tubercles;  these  are  the  result  of 
a  combination  of  processes^proliferation,  })hagocytosis,  and  degen- 
eration. Large  epithelioid  cells  are  formed  from  proliferation  of  the 
endothelial  cells  of  the  reticuhim  and  vessels.  These  devour  lymphoid 
cells,  and  they  themselves  ultimately  undergo  necrosis.  Bacteria  seem 
to  exert  no  direct  influence  in  the  production  of  these  lesions,  and  were 
not  found  in  the  nodes. 

The  lesions  are  believed  to  be  due  to  the  absorption  of  the  toxic 
products  of  the  diphtheria  bacilli  and  other  organisms. 

The  lesions  found  in  the  tonsils  differed  somewhat  from  those  seen 
in  other  lymphoid  structures.  They  were  constantly  present,  and  in 
most  cases  more  pronounced  than  in  the  glands. 

Thymus. — Flexner  studied  the  changes  in  the  thymus  gland  in 
experimentally  induced  diphtheria  in  animals.  He  called  attention  to 
the  frecjuency  with  which  the  degenerated  cells  occurred  in  the  neigh- 
borhood of  the  Hassel  bodies.  The  changes  in  general  were  similar 
to  those  observed  in  the  lymph  nodes. 

Councilman,  Mallory,  and  Pearce  examined  the  thynuis  in  20  cases. 
The  principal  change  found  was  degeneration  of  the  lymphoid  cells. 
The  degenerated  cells  were  usually  seen  in  large  cells  with  vesicular 
nuclei;  the  changes  were  most  marked  in  the  vicinity  of  the  Hassel 
bodies.  There  was  dilatation  of  the  lymphatics  and  hyaline  degen- 
eration of  the  walls  of  the  vessels.  No  bacteria  were  found  in  the 
sections. 

Skeletal  Muscles. — Councilman,  jMallory,  and  Pearce  state  that  where 
fatty  degenerations  of  the  heart  and  the  nervous  system  are  present,  a 
similar  change  will  be  found  in  the  skeletal  muscles.  In  one  case  in 
which  the  nerve  fibres  of  the  central  nervous  system  and  of  the  per- 
ipheral nerves  showed  marked  fatty  degeneration,  the  muscles  of  the 
tongue,  of  the  ulnar  side  of  the  forearm,  the  sartorius  muscle,  and  the 
biceps  of  the  thigh  exhibited  a  similar  degeneration. 

In  another  case  where  fatty  degeneration  of  the  heart  and  nervous 
system  was  pronounced  the  muscles  of  the  tongue,  the  diaphragm,  and 
the  tibialis  anticus  were  likewise  degenerated. 


670  DIPHTHERIA 

Pancreas,  Adrenals,  Thyroid  Gland,  Salivary  Glands,  Testicles, 
Pituitary  Body. — No  gross  changes  were  observed  in  these  glands  by 
Councilman,  Mallory,  and  Pearce;  neither  did  a  careful  microscopic 
examination  reveal  the  presence  of  pathological  changes. 

In  one  case  the  submaxillary  gland  showed  superficial  necrosis  and 
purulent  infiltration  due  to  extensive  inflammation  from  the  throat. 

Welch,  Flexner,  and  Wright  commonly  observed  congestion,  hemor- 
rhage, and  focal  necrosis  in  the  adrenal  glands  in  experimental  diph- 
theria, but  such  changes  apparently  do  not  occur  in  this  disease  in  the 
human  subject. 

Nervous  System. — Councilman,  Mallory,  and  Pearce  refer  to  a  study 
of  certain  nerve  structures  made  in  28  of  their  cases  by  Thomas  and 
Steensland.  The  cases  were  selected  either  on  account  of  the  presence 
of  cardiac  symptoms,  paralysis,  or  the  severity  of  the  disease.  Various 
cranial  and  other  nerves  were  submitted  to  careful  microscopic  study. 
In  all  of  them  some  grade  of  fatty  degeneration  was  noted.  The  degen- 
eration seems  almost  invariably  to  begin  in  the  myelin  sheath.  The 
change  in  the  axis  cylinder  consists  chiefly  of  an  irregular  swelling 
which  often  causes  it  to  present  a  beaded  appearance. 

The  cerebrum  was  examined  five  times,  the  cerebellum  twice,  the 
pons  three  times,  the  medulla  four  times,  and  the  cord  seven  times. 
In  all  of  these  examinations  a  varying  degree  of  fatty  degeneration  was 
present  in  the  white  substance.  The  same  change  was  noted  in  the 
anterior  and  posterior  nerve  roots. 

In  general  it  may  be  said  that  a  slight  to  a  marked  diffuse  fatty  degen- 
eration, involving  the  central  nerve  fibres  and  their  peripheral  exten- 
sions, occurs  in  certain  cases  of  diphtheria. 

Bone-marrow. — Councilman,  Mallory,  and  Pearce  examined  the 
bone-marrow  in  48  cases  of  diphtheria.  Of  this  number  all  but  3  were 
children.  In  all  of  the  cases  the  marrow  was  hyperplastic,  although  in 
the  3  adults  the  hyperplasia  was  less  pronounced.  In  the  latter  the 
marrow  was  reddish  with  areas  of  yellow  fat. 

In  the  children  the  marrow  varied  in  appearance,  but  was  usually 
red,  of  firm  consistency,  and  removable  in  solid  pieces. 

Very  little  connective  tissue  was  found  in  the  marrow,  and  that  was 
along  the  arteries.  The  veins  were  numerous  and  the  walls  like  those 
of  capillaries;  it  is  through  these  thin  walls  that  the  marrow  cells  appear 
to  enter  the  blood. 

The  changes  in  the  marrow  in  diphtheria  are  not  distinctive  of  the 
disease,  as  they  are  also  found  in  other  infectious  diseases. 

Blood. — According  to  Baginsky  there  is  an  increased  coagulability 
of  the  blood  in  diphtheria  due  to  the  action  of  the  toxin  on  the  blood 
stream  through  weakness  of  the  heart,  and  also  as  a  result  of  the  lowered 
blood  pressure  and  changes  in  the  lining  of  the  bloodvessels.  This,  it 
is  claimed,  may  lead  to  the  formation  of  thrombi  in  the  heart  or  blood- 
vessels. In  severe  septic  cases  a  thinning  or  dissolution  of  the  blood 
occurs,  which  may  cause  hemorrhages  in  various  tissues. 

The  specific  gravity  is  said  by  Grawitz  to  be  raised  at  the  height  of 


77//';  I'ATIIOIAJdY  ()/<'  bll'IITllHUIA  f;71 

the  disease,  both  in  (h'phtheria,  in  man,  and  in  exyx'rirnenf;)!  (li])lith('ria 
in  animals. 

Red  Cells.  -Diii'i  11  <^f  the  first  f(^w  (hiys  of  the  disease  the  red  eorjjuscles 
are  about  normal  in  number,  according  to  the  investigations  of  Morse, 
Ewing,  Engel,  and  Billings.  From  the  fifth  to  the  fifteenth  days,  liillings 
observed  an  average  loss  of  510,000  cells  per  cubic  millimetre.  The  loss 
ranged  from  470,000  on  the  third  day  to  2,040,000  on  the  sixth.  These 
were  in  cases  not  treated  by  antitoxin.  Of  2?>  severe  and  carefully 
counted  cases  treated  with  antitoxin,  3  alone  exhibited  a  reduction  in 
the  erythrocytes,  the  loss  being  less  than  400,000  cells  per  cubic  centi- 
metre. 

Cabot  remarks  that  "antitoxin  largely  prevents  the  ana'mia  which 
usually  develops  in  the  first  five  to  ten  days."  Healthy  persons  receiving 
antitoxin,  according  to  a  study  of  15  cases  by  Billings,  show  a  moderate 
loss  of  red  cells  in  about  one-half  of  the  cases;  the  greatest  diminution 
observed  was  930,000  per  cubic  millimetre. 

Haemoglobin .^ — A  reduction  in  the  hajmoglobin  occurs  coincidently 
with  the  diminution  in  the  number  of  red  cells,  but  restoration  of  the 
former  takes  place  more  slowly  than  the  latter.  Billings  states  that  in 
cases  treated  without  antitoxin  an  average  loss  of  10  per  cent,  was 
noted;  whereas,  when  antitoxin  was  administered  the  reduction  of  the 
haemoglobin  was  less  marked. 

Leukocytes. — Gabritschewsky,  in  1894,  was  the  first  to  point  out  the 
more  or  less  constant  hyperleukocytosis  in  diphtheria.  He  demon- 
strated by  animal  experimentation  that  the  increase  in  the  white  cells 
was  due  to  the  action  of  the  diphtheria  toxin. 

Morse  found  a  leukocytosis  in  26  out  of  30  cases,  Ewing  in  49  out  of 
53,  and  Billings  in  34  out  of  36  cases.  The  grade  of  the  leukocytosis  is 
in  a  general  way  proportionate  to  the  severity  of  the  disease.  Morse 
observed  very  high  counts  in  the  fatal  septic  cases. 

Cabot  says  that  when  leukocytosis  is  absent  the  cases  are  either  very 
mild  or  very  severe,  conditions  analogous  to  those  noted  in  pneumonia 
and  septicsemia.  The  counts  range  from  normal  to  48,000  (Morse), 
or  to  38,000  (Billings).  Bouchut  counted  over  75,000  white  cells  per 
cubic  millimetre  in  some  of  his  cases,  and  Felsenthal  found  148,229 
in  one  case. 

The  white  cells  ordinarily  increase  as  the  disease  progresses,  and 
decrease  as  convalescence  sets  in. 

According  to  Ewing,  the  leukocyte  count  is  not  influenced  by  the 
use  of  the  antitoxin  serum,  except  during  the  first  twenty-four  hours 
after  its  injection.  Within  thirty  minutes  the  leukocytes  are  said  to  be 
considerably  diminished. 

Engel  states  that  antitoxin  in  the  beginning  causes  a  slight  increase 
in  the  percentage  of  lymphocytes;  in  some  cases  the  increase  is  pro- 
nounced.   In  one  case  after  injection  they  rose  from  24  to  65  per  cent. 

Engel  also  emphasizes  the  bad  prognostic  import  of  the  presence  of 
a  considerable  number  of  myelocytes. 

It  is  generally  conceded  that  an  examination  of  the  blood  in  diph- 


672  DIPHTHERIA 

theria  lends  little  or  no  aid  in  diagnosis.  The  absence  of  leukocytosis 
and  the  presence  of  a  considerable  number  of  myelocytes  would  seem 
to  be  of  ill  augury. 

THE  DIAGNOSIS  OF  DIPHTHERIA. 

As  diphtheria  is  a  communicable  disease  with  a  decided  predilection 
for  young  children,  among  whom  it  is  also  most  fatal,  it  is  important 
that  an  early  diagnosis  should  be  made,  both  with  regard  to  prevention 
and  treatment.  Without  a  history  of  previous  exposure  to  the  infection 
it  is  confessedly  difficult  to  recognize  the  disease  in  its  very  earliest 
manifestations;  for  there  is  no  throat  affection  more  varied  in  its  clinical 
aspect  and  more  deceptive  in  its  initial  stage  than  diphtheria.  But, 
fortunately,  the  disease  is  not  long  in  revealing  its  true  nature.  In  the 
majority  of  cases  the  diagnosis  is  not  difficult  after  the  affection  has 
continued  for  twenty-four  hours,  since  by  this  time  the  characteristic 
exudation  may  be  seen  on  the  tonsils  or  some  part  of  the  fauces.  When 
thus  clearly  marked  the  nature  of  the  throat  disease  is  at  once  apparent 
on  the  first  examination. 

But  all  cases  are  not  so  readily  diagnosticated,  even  by  experienced 
physicians.  Neglecting  to  inspect  the  throat  of  a  child,  who  is  feverish 
and  indisposed,  may  sometimes  be  a  reason  for  failure  in  making  an 
early  diagnosis.  While  sore  throat  is  one  of  the  earliest  symptoms  of 
diphtheria,  yet  it  is  a  fact  that  many  children,  even  those  old  enough 
to  make  known  their  sensations,  do  not  complain  of  the  throat  until 
the  disease  has  made  considerable  progress. 

On  his  first  visit  to  a  child,  on  account  of  whose  illness  he  has  been 
summoned,  the  physician  should  be  careful  to  examine  the  fauces, 
especially  when  diphtheria  is  prevailing  in  the  neighborhood.  In  this 
way  the  disease  may  be  discovered  early  and  its  spread  to  other  members 
of  the  family  prevented. 

In  well-marked  cases  it  is  usually  not  difficult  to  make  the  diagnosis. 
In  doubtful  cases  it  may  be  helpful  to  know  whether  the  patient  has 
been  recently  exposed  to  the  infection  of  diphtheria,  scarlet  fever,  or 
some  other  infectious  disease.  If  exposure  to  diphtheria  is  known  to 
have  occurred,  the  mildest  form  of  sore  throat  should  be  regarded  with 
suspicion  and  carefully  watched  for  further  development.  But,  in  a 
section  of  the  country  where  diphtheria  is  not  prevailing,  it  is  probable 
that  a  sore  throat  presenting  some  of  the  characteristics  of  the  disease 
will  turn  out  to  be  something  else. 

It  sometimes  happens  that  an  early  diagnosis  is  not  made  because 
the  exudation  is  concealed  in  the  crypts  of  the  tonsils,  or  in  some  other 
depressions  of  the  faucial  surface.  When  thus  located  it  may  be  brought 
into  view  by  pushing  the  tongue  depressor  far  back  on  the  tongue  and 
causing  the  child  to  retch  slightly;  or  these  surfaces  may  be  exposed 
to  view  by  having  an  assistant  make  firm  pressure  on  the  neck  near  the 
angle  of  the  jaw  while  an  examination  of  the  throat  is  being  made. 

In  some  cases  it  is  impossible  to  make  a  positive  diagnosis,  clinically, 


77/ A'  DIAdNOShH  OF  1)1 1'lll'll  Fill  A  073 

until  the  disease  h;is  been  under  ()[)servati()M  for  two  or  three  days. 
Tiiis  is  more  (!Sj)eeially  triu;  in  some;  forms  of  nasal  diphtlieria,  without 
involvement  of  the  fauces  to  a  greater  ext(;nt  than  the  oeeurrenee  f)f 
a  general  hypenemia.  The  uneven  surface  of  the  cavities  of  the  nose 
favors  concealment  of  the  disease  until  it  has  made  some  progress.  It 
may  then  be  discovered  either  by  insjx'cting  the  nares  at  their  external 
orifices,  or  by  an  examination  with  a  nasal  speeuhnn.  In  nasal  flij;h- 
theria  there  is  apt  to  be  a  mucopurulent  diseharg(;  from  the  nose, 
and  when  there  are  seen  in  this  discharge  small,  white  specks,  exudate 
is  probably  present,  although  it  may  not  yet  be  visible.  It  usually, 
however,  makes  its  appearance  before  the  disease  terminates. 

There  are  no  prodromata  that  are  peculiar  to  (iij)htheria.  The 
general  malaise,  followed  by  headache,  nausea  and  vomiting,  so 
commonly  seen,  are  the  forerunners  of  many  other  affections  also. 
Even  the  sore  throat,  pain  in  swallowing,  tenderness  of  the  glands  near 
the  angle  of  the  jaw,  and  swelling  of  the  neck  are  all  present  in  the 
ordinary  forms  of  tonsillitis.  The  distinguishing  feature  of  diphtheria 
is  the  peculiar  exudation  that  appears  upon  the  mucous  membrane, 
particularly  in  the  fauces.  A  knowledge  of  the  fact  that  this  exudation 
takes  place  not  only  into  the  epithelium,  but  also  into  the  subepithelial 
tissue,  is  helpful  only  to  a  limited  extent  in  solving  the  problem  of 
diagnosis.  Indeed,  in  many  severe  cases  the  diphtheritic  process  does 
not  penetrate  deeply  into  the  mucous  membrane,  as  it  peels  off  quickly 
and  leaves  only  small  areas  of  superficial  ulceration.  On  the  other  hand, 
an  exudation  of  streptococcic  origin  is  sometimes  very  adherent,  and 
its  disappearance  may  be  followed  by  marked  ulceration  of  the  mucous 
membrane.  But  in  most  streptococcic  affections  of  the  throat,  certainly 
in  the  milder  varieties,  the  disease  is  limited  to  the  tonsils,  and  the 
greater  part  of  the  exudation  may  be  removed  with  a  cotton  swab. 

In  considering  the  diagnostic  feature  of  the  diphtherial  membrane 
it  is  necessary  to  recall  some  of  its  characteristics  already  described. 
It  is  deposited  not  only  on  the  tonsils,  but  frequently  also  on  the  pillars 
of  the  fauces,  the  soft  palate,  the  pharyngeal  wall,  in  the  nares,  and  in 
the  larynx.  One  of  the  peculiarities  of  the  meml)rane  is  that  it  is  liable 
to  start  on  some  of  the  small  prominences  of  the  fauces,  such  as  the 
uvula,  epiglottis,  and  the  like.  As  already  mentioned,  it  is  also  liable 
to  form  in  some  of  the  small  recesses,  such  as  the  lacunfe  of  the  tonsils 
and  the  ventricles  of  the  larynx.  The  formation  of  membrane  on  the 
uvula,  especially  on  its  posterior  surface,  is  believed  by  some  writers 
to  be  almost  pathognomonic.  When  seen  on  the  sides  of  the  uvula  it 
is  quite  sure  to  be  present  on  its  posterior  surface  also.  Frequently 
the  entire  uvula  is  invested  with  membrane,  which  is  often  shed  as  a 
complete  cast,  resembling,  as  Trousseau  has  said,  the  finger  of  a  glove. 

When  the  diphtherial  exudation  is  examined  carefully  it  is  found  to 
be  distinctly  membranous.  It  is  of  a  yellowish-white  color,  and  when 
exfoliated  in  large  pieces  or  casts  and  allowed  to  float  in  water  it  bears 
a  strong  resemblance  to  pieces  of  chamois  skin.  Lennox  Browne's 
description  of  the  exudation  is  worth  repeating.     He  says  it  "begins 

43 


674  DIPHTHERIA 

almost  invariably  as  a  thin,  bluish-white  deposit,  something  like  a 
shaving  from  the  boiled  white  of  an  egg  of  the  duck,  goose,  or  plover. 
As  the  deposit  increases  in  thickness,  it  gradually  becomes  more  white 
and  opaque,  resembling  the  boiled  albumen  of  a  fowl's  egg,  or  it  may 
then  partake  of  a  very  pale  lemon  tint.  Then  it  becomes  of  a  yellowish 
or  greenish  gray,  brown,  and  sometimes  almost  black,  as  the  necrotic 
process  advances,  or  as  blood  is  extra vasated.  Only  in  the  comparatively 
uncommon  case  of  a  lacunar  diphtheria  do  we  see  the  exudation  com- 
mencing as  discrete  spots  of  deposit,  which  may  be  of  a  yellow  color 
at  the  very  first  onset,  and,  even  when  coalesced,  may  never  exhibit 
the  pearly  or  opalescent  appearance  which  characterizes  the  more 
ordinary  form  on  its  first  manifestation."  He  adds,  "The  membrane 
is  sometimes  plastered,  as  if  put  on  with  a  palette  knife,  or  laid  on  with 
a  trowel."  This  latter  comparison  applies  with  much  aptness  to  what 
is  seen  when  the  entire  fauces  and  soft  palate  are  covered  with  the 
exudation. 

Adenitis,  or  more  or  less  enlargement  and  tenderness  of  the 
lymphatic  glands  of  the  neck,  is  a  symptom  rarely  absent.  Its  im- 
portance depends  to  some  extent  on  the  region  in  which  the  glands 
are  involved,  and  the  degree  of  inflammation  and  swelling.  In  mild 
tonsillar  diphtheria  the  cervical  glands  alone  are  swollen,  but,  as  a  rule, 
only  very  slightly.  In  the  more  severe  cases,  including  the  complex 
or  septic  form  of  the  disease,  the  whole  chain  of  cervical  glands  is 
converted  into  one  large  mass.  The  inflammatory  enlargement  includes 
also  the  periglandular  cellular  tissue.  In  such  cases  not  only  the 
cervical,  but  the  submaxillary  and  sometimes  the  parotid  glands  are 
affected. 

Catarrhal  Croup. — ^There  is  frequently  some  difficulty  in  distinguish- 
ing between  membranous  croup  in  its  early  stage,  and  catarrhal,  spas- 
modic, or  non-specific  croup.  But  if  a  few  of  the  principal  points  of 
difference  be  borne  in  mind  the  difficulty  should  not  be  very  great. 
For  instance,  in  membranous  croup  the  symptoms  are  progressive, 
being  as  well  marked  in  the  day-time  as  in  the  night.  The  hoarseness 
gradually  increases,  so  that  the  child  in  a  short  time  can  speak  only 
in  a  whisper.  The  breathing  becomes  more  and  more  obstructed  as 
the  exudation  increases;  the  temperature  reaches  100°  to  103°  F.,  and  the 
child  constantly  grows  more  restless  and  cyanotic.  There  is  marked 
recession  of  the  ensiform  process  of  the  sternum,  and  of  the  lower  ribs. 
These  symptoms  are  not  relieved  by  the  relaxing  influence  of  an  emetic. 
Moreover,  the  characteristic  exudation  may  be  present  in  the  fauces. 
On  the  other  hand,  in  catarrhal  or  spasmodic  croup  the  symptoms  are 
usually  intermittent,  being  due  to  a  paroxysmal  spasm  of  the  glottis, 
resulting  from  subacute  laryngitis.  In  the  vast  majority  of  instances 
the  affection  occurs  at  night-time,  and  more  often  in  the  early  part  of 
the  night.  During  the  day  the  symptoms,  if  present  at  all,  are  usually 
much  more  moderate.  The  duration  of  the  paroxysm  varies  from  a 
few  minutes  to  several  hours.  The  voice,  though  hoarse,  is  very  rarely 
quite  extinct  or  whispering,  and  scarcely  ever  more  than  temporarily  so. 


77//';  DIAdNOHIH  OF  1)1 1'llTII l<:UIA  075 

This  is  a  diagnostic  point  of  niucb  value  in  (Jistinguisliing  Ijetwccn  tlip 
two  forms  of  crouj).  In  sj)asnio(Jic  croup  an  cnictic  generally  gives 
relief,  but  does  not  in  membranous  erouj).  The  fauees  are  free  from 
exudate. 

Pseudodiphtheria.  We  have  already  remarked  that  a  membranous 
sore  throat,  in  whi(;h  the  streptococcus  is  the  principal  if  not  the  sole 
orgaiu'sni  present,  sometimes  occurs,  and  we  have  pointed  out  some  of 
the  characteristics  of  this  ad'ection  in  comjjarison  with  those  of  true 
diphtheria.  We  repeat  that,  as  a  rule,  in  true  diphtiieiia  the  exudate 
is  so  intimately  connected  with  the  mucous  membrane  that  it  cannot 
be  removed  without  injuring  the  parts,  while  in  pseuflodiphtheria  it 
lies  upon  the  surface  and  may  be  quite  readily  removcf].  It  must  be 
admitted,  however,  that  there  are  many  exceptions  to  this  rule.  The 
physician,  therefore,  will  often  find  it  impossible  to  make  a  positive 
diagnosis  without  a  culture  and  a  microscopic  examination. 

Follicular  Tonsillitis. — There  is  perhaps  no  throat  affection  more 
often  mistaken  for  diphtheria  than  follicular  tonsillitis.  It  is  a  very 
common  disease,  being  more  frequently  seen  in  some  families  than  in 
others.  It  sometimes  spreads  as  though  it  were  contagious.  It  begins 
with  sore  throat,  fever,  and  tenderness  in  the  neck  below  the  angle  of 
the  jaw.  There  is  often  a  good  deal  of  constitutional  disturbance,  such 
as  high  temperature,  headache,  and  chilliness,  with  sometimes  pain  in 
the  back  and  extremities.  The  fauces  at  first  are  hypersemic,  but  the 
tonsils  soon  become  enlarged  and  dotted  over  with  rounded  masses 
of  whitish  material  of  pinhead  size.  These  dots  frequently  coalesce, 
forming  quite  large  patches,  particularly  in  the  crypts  of  the  tonsils. 
The  dots  or  patches  consist  of  a  peculiar  secretion  having  incorporated 
with  it  epithelial  cells.  It  differs  from  the  diphtherial  exudate  in  that 
it  is  readily  detached  by  a  swab.  The  cheesy  dots  that  form  on  the 
tonsils  will,  when  crushed  between  the  thumb  and  finger,  emit  a  fetid 
odor.  The  disease  is  of  short  duration,  and  is  not  followed  by  sequel [e. 
The  diagnosis  is  easily  made,  except  in  some  cases  of  the  mildest  form 
of  diphtheria  when  dift'erentiation  may  be  difficult.  In  acute  quinsy 
the  jaws  are  stiff,  and  there  is  often  considerable  difficulty  in  opening 
the  mouth  sufficiently  wide  for  a  satisfactory  inspection  of  the  fauces. 
Where  any  doubt  is  felt  as  to  the  nature  of  the  affection  it  may  be 
readily  dispelled  by  a  bacteriological  examination. 

Herpetic  Pharyngitis. — There  is  usually  no  great  diflaculty  in  recog- 
nizing an  herpetic  pharyngitis,  but,  like  follicular  tonsillitis,  it  is  occa- 
sionally mistaken  for  mild  diphtheria.  If  seen  in  the  early  stage,  before 
the  minute  vesicles  have  disappeared,  the  diagnosis  is  easily  made; 
but  the  ulcers  that  remain  often  show  a  whitish  covering,  which  has 
often  been  mistaken  for  diphtherial  exudate.  As  the  ulcers  are  very 
small,  the  whitish  concretions  are  usually  seen  in  the  form  of  dots. 
It  is  only  when  these  concretions  unite  and  form  a  patch  that  any 
difficulty  is  experienced  in  the  diagnosis.  It  has  been  said  that  the 
presence  of  an  herpetic  eruption  on  some  other  part  of  the  body  would 
afford  presumptive  evidence  that  the  throat  affection  was  of  the  same 


676  V  DIPHTHERIA 

nature,  but  we  have  often  seen  herpes  labiaHs  in  children  suffering 
from  diphtheria.  Fortunately,  in  these  diseases  the  clinician  does  not 
have  to  base  his  diagnosis  upon  symptoms  alone;  he  can  invoke  the 
aid  of  bacteriology. 

Gangrenous  Pharyngitis. — In  our  experience  gangrenous  pharyngitis 
is  rare  in  diphtheria.  We  do  not  recall  having  seen  a  single  case.  The 
affection,  however,  is  not  uncommon  in  scarlet  fever.  The  ulcerative 
action  and  loss  of  tissue  are  much  more  extensive  than  that  which  is 
seen  in  diphtheria.  The  necrotic  tissue  resulting  from  the  gangrenous 
process  has  often  been  mistaken  for  diphtherial  exudate.  The  pseudo- 
membrane  in  this  variety  of  sore  throat  is,  from  the  beginning,  of  a 
dark-gray  or  brownish  color,  and  is  exceedingly  offensive.  On  the  other 
hand,  the  pseudomembrane  of  diphtheria  is  white  or  yellowish-white 
in  the  commencement,  and  continues  so  to  the  end  unless  it  becomes 
stained  with  blood.  The  foetor  in  the  latter  disease  is  mild  in  comparison 
with  the  former.  The  diagnosis  is  not  difficult  if  the  case  comes  under 
observation  at  the  beginning. 

Stomatitis.' — In  diffuse  inflammation  of  the  mucous  membrane  of 
the  mouth  the  small  ulcers  that  commonly  appear  show  a  whitish 
covering.  This  condition  not  infrequently  increases  to  the  extent  that 
many  of  these  ulcers  coalesce,  forming  patches  consisting  of  a  whitish, 
curd-like  matter;  and  the  affection  often  extends  gradually  to  the  roof 
of  the  mouth,  the  inside  of  the  cheeks,  and  may  even  reach  the  pharynx. 
The  exudation  is  usually  thin,  and  sometimes  covers  evenly  a  large 
part  of  the  mucous  membrane  of  the  mouth,  but  more  commonly  it  is 
seen  in  irregularly  scattered  patches  and  points.  When  the  disease 
assumes  this  appearance  it  is  occasionally  confounded  with  diphtheria. 
In  making  a  diagnosis  it  is  important  to  note  that  the  exudation  is  thin 
and  filmy;  it  never  becomes  membranous.  On  parts  where  it  is  thicker 
it  is  curdy  or  cheesy. 

We  have  known  gangrenous  stomatitis  and  even  syphilitic  sore  throat 
to  have  been  mistaken  for  diphtheria.  In  view  of  the  general  character- 
istics of  these  affections  the  diagnosis  is  not  difficult. 

The  presence  of  albumin  in  the  urine  in  diphtheria  deserves  some 
notice  as  a  diagnostic  sign.  We  have  found  it  in  quite  a  large  pro- 
portion of  our  cases  in  which  the  urine  was  examined.  Its  presence 
would  be  of  still  greater  diagnostic  importance  were  it  not  true  that  it  is 
occasionally  found  in  some  other  varieties  of  inflammation  of  the  throat. 

Since  the  advent  of  bacteriology  as  a  science  the  clinician  has  at  his 
command  a  most  useful  means  of  determining  the  diagnosis  of  diph- 
theria in  all  doubtful  cases.  While  every  well-informed  physician 
should  be  familiar  with  the  clinical  evidences  of  the  disease,  yet  as  the 
clinical  disguises  of  this  throat  affection  are  so  varied  it  is  fortunate 
that  the  doubtful  points  of  diagnosis  can  be  solved  by  bacteriology. 
Therefore,  any  consideration  of  the  subject  of  diagnosis  in  diphtheria 
would  be  regarded  as  incomplete  at  the  present  day  without  some 
reference  to  the  means  employed  to  determine  the  presence  of  the 
Klebs-Loeffler  bacilli  in  the  pseudomembrane. 


77//';  i)iA(JN()Sis  OF  nii'ii'i'iiKin  \  677 

The  Bacteriological  Diagnosis  of  Diphtheria. 

In  a  patient  presenting  .suspicious  cliuicjil  evidences  of  diplillicria, 
the  diagnosis  may  Ix^  firmly  estahlislied  by  determining  the  [jresence 
or  al)sence  of  the  di})hth(;ria  hacilH  in  the  false  inenihrane.  'i'his  may 
be  accomplished  by  examination  of  (a)  smears,  and  (b)  cultures. 

Smears. — In  a  large  ])ercentage  of  cases  a  satisfncfory  result  may 
be  obtained  from  an  inunediate  microscopic  examinafion  of  the  exudate 
present.  A  cover-glass  is  smeared  with  material  taken  from  the  throat 
by  means  of  a  swab.  The  cover-glass  preparation  is  allowed  to  flrv, 
is  then  passed  several  times  through  a  flame  to  fix  the  albumin,  and  is 
finally  stained  witli  Loeffler's  solution  of  methylene  blue.  By  this  means 
the  presence  or  absence  of  bacilli  may  often  be  determined  in  a  few 
minutes. 

The  rapidity  with  which  the  examination  can  be  made  makes  it  a 
procedure  of  great  value,  particularly  where  an  immediate  diagno.sis  is 
a  matter  of  great  importance.  We  have  examined  a  considerable 
number  of  smears  at  the  Municipal  Hospital,  and  in  these  casts  we 
were  enabled  in  the  vast  majority  of  cases  to  predict  the  subsefpient 
cultural  findings. 

The  procedure  just  mentioned,  however,  has  only  a  relative  value 
and  should  not  be  depended  upon  to  the  exclusion  of  the  culture.  The 
bacilli  found  in  smears  are  ordinarily  much  less  typical  than  those 
grown  upon  culture  media,  and  the  chances  of  contamination  are 
greater.  Abbott^  says:  "There  are  other  organisms  present  in  the 
mouth  cavity,  particularly  in  the  mouths  of  persons  having  decayed 
teeth,  the  morphology  of  which  is  so  like  that  of  the  bacillus  of  diph- 
theria that  they  might  easily  be  mistaken  for  that  organism,  if  subjected 
only  to  the  usual  method  of  microscopic  examination."  He  adds, 
however,  that  where  there  is  suspicious  clinical  evidence  the  direct 
examination  of  smears  will  serve  to  confirm  or  negative  the  diagnosis 
in  the  vast  majority  of  cases. 

Cultures. — Cultures  are  ordinarily  made  with  a  swab,  although  a 
platinum  loop  may  be  employed  for  the  purpose.  The  swab  consists 
of  absorbent  cotton  wrapped  around  the  end  of  a  piece  of  heavy  w'uq. 
The  swab,  enclosed  ordinarily  in  a  plugged  test-tube,  is  sterilized  by  heat. 

In  taking  the  culture  the  tongue  should  be  depressed  by  means  of 
a  spoon  or  depressor,  and  the  swab  firmly  rubbed  over  the  surface  of 
the  membrane.  When  no  membrane  is  present,  the  swab  should  be 
brought  in  contact  with  the  tonsils,  faucial  pillars,  and  pharyngeal 
wall.  When  laryngeal  symptoms  alone  are  present,  the  swab  should 
be  introduced  as  far  down  as  possible.  The  moistened  cotton  is  then 
rubbed  lightly  over  the  surface  of  a  tube  of  Loeffler's  blood  serum,  care 
being  taken  to  carefully  replace  the  cotton  plug.  The  swab  containing 
the  remains  of  the  infected  material  should  be  returned  to  its  own  tube 
and  subsequently  destroyed  or  disinfected. 

1  The  Principles  of  Bacteriology,  5th  ed.,  1899,  p.  361. 


678  DIPHTHERIA 

Great  care  should  be  taken  not  to  make  the  culture  directly  after 
antiseptic  applications  have  been  applied  to  the  throat.  It  is  well,  in 
such  cases,  to  wait  a  half-hour  or  an  hour  before  culturing.  The 
inoculated  tubes  are  incubated  at  a  temperature  of  from  99°  to  100°  F. 
(37°  C.)  for  twelve  to  fourteen  hours,  at  the  end  of  which  time  the 
colonies  may  be  examined. 

The  gross  appearances  of  the  culture  are  more  characteristic  at  the 
end  of  twenty-four  hours.  The  diphtheria  bacillus  grows  so  much  more 
rapidly  than  other  mouth  organisms  upon  the  surface  of  Loeffler's  blood 
serum  that  they  are  often  the  only  conspicuous  colonies  present.  The 
colonies  are  large,  round,  grayish-white  or  cream-colored,  elevated 
with  irregular  periphery,  which  is  less  dense  in  the  centre. 

Examination  of  Cultures.— A  drop  of  sterile  water  is  placed  upon  a 
clean  cover-glass  and  rubbed  up  with  a  couple  of  colonies  which  have 
been  detached  from  the  culture  media  with  a  platinum  loop.  The 
preparation  is  allowed  to  dry  in  the  air  and  is  then  passed  several  times 
through  the  flame  of  a  Bunsen  burner  or  alcohol  lamp.  It  is  then 
covered  with  Loeffler's  alkaline  solution  of  methylene  blue  for  ten 
minutes,  after  which  it  is  rinsed,  dried,  and  mounted  in  balsam. 

The  specimen  is  examined  with  a  one-twelfth-inch  oil-immersion  lens. 
Diphtheria  bacilli  may  be  found  in  pure  culture,  or  micrococci  of  different 
varieties  may  also  be  present. 

In  order  to  test  the  virulence  of  diphtheria  bacilli  a  guinea-pig  is 
subcutaneously  injected  with  a  small  quantity  of  a  pure  culture  in 
bouillon.  Death  results  in  from  twenty-four  hours  to  five  days,  usually 
within  seventy-two  hours. 

There  is  intense  oedema  with  congestion  and  hemorrhage  at  the 
site  of  injection.  The  changes  in  the  other  tissues,  according  to  Abbott, 
are  as  follows:  Swollen  and  reddened  lymphatic  glands,  increased 
serous  fluid  in  the  peritoneum,  pleura,  and  pericardium;  enlarged  and 
hemorrhagic  adrenal  bodies;  occasionally  slightly,  swollen  spleen;  and 
sometimes  fatty  degeneration  in  the  liver,  kidney,  and  myocardium. 
The  bacilli  are  always  to  be  found  at  the  site  of  inoculation,  most 
abundantly  in  the  grayish-white,  fibrinopurulent  exudate. 

THE  PROGNOSIS  OF   DIPHTHERIA. 

The  forecast  of  diphtheria  cannot  be  made  with  any  degree  of 
certainty.  The  disease  itself,  to  say  nothing  of  the  complications  that 
are  liable  to  occur,  is  so  treacherous  that  it  is  almost  impossible  to 
predict  a  favorable  ending  of  any  attack  however  mild  the  earlier 
symptoms  may  be.  Not  infrequently  cases  that  appear  to  be  mild  in 
the  beginning  and  give  the  best  promise  of  recovery  suddenly  change 
into  a  severe  form  through  extension  of  the  diphtheritic  process  into 
the  larynx,  or  the  development  of  some  dangerous  secondary  affection. 
On  the  other  hand,  cases  that  begin  with  marked  severity,  giving  rise 
to  gloomy  forebodings,  often  take  a  favorable  change  and  speedily 
end  in  ^recovery. 


Tim  PiiocNOHJH  OF  j)ii'iiriii<:iiiA  071) 

So  variable  are  the  elements  of  prognosis  in  diphtheria  that  tliey 
cannot  be  considered  from  any  single  standpoint.  C)ne  mnst  take 
into  consideration  the  prostrating  efl'ects  of  the  toxins  of  the  disease; 
the  history,  enviromnent,  and  age  of  tlu;  f)atient;  the  complications 
affecting  vital  parts  during  the  course  of  the  attack,  and  the  nature  of 
the  secjuehe.  Likewise,  the  character  of  the  prevailing  epidemic  must 
be  taken  into  account.  In  some  epidemics  a  large  proportion  of  the 
cases  are  mild,  and  the  death  rate  is  low.  In  other  epidemics,  or  in  sr>me 
localities,  the  disease  assumes  a  more  severe  form,  and,  in  spite  of  the 
best  treatment,  the  proportion  that  perish  is  much  larger.  A  death  rate 
as  high  as  60  per  cent,  has  been  reported;  while  in  very  rnihl  epidemics 
it  has  been  as  low  as  5  to  10  per  cent. 

It  is  a  question  whether  social  status  and  domestic  surroundiricjs  have 
as  much  to  do  in  determining  the  character  of  the  disease  as  is  generally 
supposed.  It  is  true,  however,  that  when  diphtheria  breaks  out  in  an 
institution  for  children,  especially  foundlings,  it  is  apt  to  be  attended 
with  great  fatality.  In  our  experience  the  patients  sent  to  the  hospital 
from  careless  and  indigent  families  are  not  more  liable  to  suffer  from 
severe  diphtheria  than  those  which  come  from  better  and  more  sanitary 
homes.  Nor  do  we  find  that  delicate  children  perish  in  a  larger  pro- 
portion than  the  robust.  In  speaking  of  the  influence  exerted  by  social 
status,  Lennox  Browne  says  it  has  appeared  to  him  "that  when  diph- 
theria attacks  members  of  the  upper  classes  it  is  often  more  malignant, 
and  runs  a  more  qiiickly  fatal  course  than  among  the  indigent;  the 
disease  finding,  as  it  w^ere,  a  more  receptive  soil  in  the  case  of  these 
delicately  nurtured  than  in  those  whose  systems  are  in  a  manner  accus- 
tomed to  insanitary  influences.  On  the  other  hand,  and  for  obvious 
reasons,  recovery  from  the  sequelae,  when  once  the  acuteness  of  the 
attack  has  passed  off,  is  more  expeditious  and  complete  in  the  well- 
to-do." 

There  can  be  no  doubt,  however,  that  when  diphtheria  is  at  all  severe, 
unsanitary  surroundings  would  contribute  toward  an  unfavorable  prog- 
nosis. The  less  adequate  the  facilities  for  caring  for  the  patient  and 
the  poorer  the  service,  the  greater  are  the  probabilities  that  the  disease 
will  spread  and  increase  in  virulence.  Where  no  attention  is  paid  to 
ventilation  of  the  sick-room,  the  vitiated  condition  of  the  atmosphere 
tends  to  lower  the  resisting  power  of  the  patient,  and  thus  diminishes 
the  chances  of  recovery. 

Idiosyncrasy,  or  any  family  susceptibility  to  diphtheria  that  may  be 
known  to  exist,  should  be  taken  into  consideration  as  affording  important 
prognostic  data.  Every  practitioner  knows  how  fatal  the  disease  is  in 
some  families.  It  is  worthy  of  notice  that  when  diphtheria  breaks  out 
in  a  family,  or  in  a  neighborhood,  children  are  almost  always  the  first  to  be 
attacked,  showing  that  in  them  the  susceptibility  to  the  disease  is  most 
marked. 

Age. — There  is  not  only  an  age  disposition  to  diphtheria,  but  there 
is  also  an  age  mortality,  and  this  must  be  taken  into  account  in  a  forecast 
of  the  disease.     The  vast  majority  of  all  deaths  from  this  affection 


680 


DIPHTHERIA 


occurs  among  children  under  five  years  of  age,  and  the  mortahty  rate 
at  this  age  period  is  vastly  higher  than  in  any  other  quinquennial  period 
of  life.  This  statement  is  confirmed  by  the  statistics  of  all  large  hos- 
pitals for  the  treatment  of  diphtheria  patients. 

The  following  table  shows  the  mortality,  according  to  age,  in  the 
Asylums'  Board  Hospitals,  London,  1892-93:^ 

Percentage. 


Age. 

Under  one  year 

f  1892 
^1893 

One  to  two  years 

fl892 
1 1893 

Two  to  three  years 

J  1892 
11893 

Three  to  four  years 

f  1892 
11893 

(1892 
Four  to  five  years       <  ^ggg 


rl892 

Five  to  ten  years        i  ,gg„ 


f  1892 
Ten  to  fifteen  years    -j  j^ggg 


f  1892 
Over  fifteen  years       ■!  .g^g 


Admitted. 

Died. 

.       49 

31 

.      40 

37 

89 

68 

.     108 

66 

.     166 

106 

274 

172 

.     163 

90 

.     219 

131 

382 

221 

.     195 

96 

.     296 

149 

491 

245 

.     240 

106 

.     339 

143 

579 

249 

.     631 

163 

.      880 

233 

1511 

396 

.     209 

15 

.     298 

30 

507 

45 

.     414 

16 

.     610 

36 

76.4 


62.7 


26.2 


5.0 


Of  1000  consecutive  cases  of  diphtheria  observed  by  Lennox  Browne 
the  age  mortality  was  as  follows: 

Age. 
Under  1  year 11 


1    to     2  years 

2    ' 

3      " 

3    ' 

4       " 

4    ' 

5       " 

5    ' 

6       " 

6     ' 

7      " 

7     ' 

8      " 

8    ' 

9      " 

9     ' 

10      " 

10    ' 

11      " 

U     ' 

12      " 

12    ' 

13      " 

13    ' 

14      " 

14    ' 

15      " 

Over 

15      " 

f  cases. 

Deaths. 

Percentages 

11 

5 

45.45 

71 

45 

63.38 

85 

34 

40.00 

117 

54 

46.15 

118 

43 

36.44 

108 

34 

31.48 

84 

24 

28.57 

57 

9 

15.78 

31 

11 

35.48 

38 

5 

13.15 

29 

8 

27.58 

20 

0 

16 

0 

22 

2 

9.00 

15 

2 

13.33 

178 

7 

3.93 

1000 


1  Lennox  Browne,  Diphtheria  and  its  Associates. 


Till':  I'UOdjMOSI.S  ()!<'  DII'li'l'IIICidA 


G81 


Classified   a(;c()nHii(^  to  (juinqucnnial   a^c   [xtIcxIs,   \\\c  cusvh  in   the 
above  tabU^  show  as  follows: 


Age.  No.  of  rji,Ki,'H. 

Under    5  yearH WZ 

5    to    10      " 31K 

10    "     15      " 102 

Over     15      " 178 

1000 


/)«fUllH. 

PcrceiitaKCH 

IHl 

45.0 

83 

26.1 

Vl 

11.7 

7 

■.•,'.)Z 

283 


2».3 


In  the  following  table  of  statisties,  including  over  9000  oases  of 
diphtheria,  which  were  treated  in  the  Municipal  Hospital,  Philadelphia, 
during  a  period  of  ten  years,  from  1893  to  1902,  iiichisive,  the  nuujljer 
of  patients  and  the  mortality  rate  within  certain  age  [xriods  are  shown: 


Under  1  year. 

1  to  5  years. 

5  to  10  years. 

10  to  15  years. 

15  to  25  years. 

25  years  and 
upward. 

•6 

•6. 

^ 

.  "^ 

. 

-c 

T3 

.  "O 

Year. 

■oii 

"O 

o 

^± 

o 

'^?. 

•o 

o 

■C  -i 

■a 

o 

■C  ^ 

•d 

o 

■6s 

13 

o 

■<^ 

0) 

s    <;^ 

o 

^■n 

a> 

t-. 

-t^.n 

a> 

"i^ 

a; 

<.t: 

0) 

u* 

H 

;; 

Ph 

U 

Q 

Ph 

■a 

« 

Oh 

ti 

O 

Q^ 

" 

ft 

P. 

b 

« 

s:, 

1893 

3 

2 

66.66 

82 

35 

42. 68 

53 

17 

32.07 

18 

3 

16.66 

36 

3     8.33 

25 

2 

8.00 

1894 

16 

i) 

56.  25 

218 

98 

44.95 

120 

36 

30.00 

31 

6 

19.35 

52 

3      5.77 

28 

2 

7.14 

1895 

25 

10 

40.  00 

327 

122 

87.3 

187 

43 

22.9 

46 

7 

15.2 

56 

4     7.1 

65 

4 

6.1 

1896 

S3 

IS 

54.54 

404 

12S 

31.68 

27  (i 

35 

12.68 

71 

5 

7.04 

49 

1      2.04 

36 

3 

8.33 

1897 

34 

16 

47.05 

560 

199i  35.53 

437 

65 

14.87 

126 

14 

11.11 

89 

3      3.37 

49 

3 

6.12 

1898 

42 

20 

47.61 

552 

200;  36.23 

447 

66 

14.76 

93 

8 

8.60 

47 

3      6.38 

48 

0 

1899 

38 

24 

63. 15    659 

181    27.46 

462 

59 

12.79 

102 

7 

6.81 

62 

2 

3.22 

50 

2 

4.00 

1900 

40 

21 

52.50,  595 

192    32.27 

473 

71 

15.01 

117 

7 

5.9S 

90 

4 

4.44 

52 

3 

5.76 

1901 

30 

15 

50.  m 

374;  Il9i  31.81 

287 

28 

9.75 

]06|     5 

4.71 

56 

6 

10.71 

36      1 

2.77 

1902 

38 

12 

31.57 

3061     97 

1 
1 

31.08 

159 
2901 

25 
445 

15. 72 

40      1 

2.5 

33 

2 

6.06 

26     0 

1 

299 

147 

49.16 

4076 

1371 

33.63 

15.33 

750    63 

8.4 

570 

31 

5.43 

1 
415!  20 

1 

4.81 

Sex. — We  see  no  reason  why  sex  should  exert  any  influence  on  the 
mortality  rate,  and  yet  according  to  our  observation,  as  well  as  that  of 
some  other  writers,  the  death  rate  among  the  males  is  almost  constantly 
in  excess  of  that  of  the  females. 

The  following  table  shows  the  mortality,  according  to  sex,  of  all  cases 
of  diphtheria  treated  in  the  Asvlums'  Board  Hospitals,  London,  from 
1888  to  1894,  inclusive:^ 

Sex.  Admitted. 

Males 5,245 

Females 6,353 

11,598 


Died. 

Per  cent 

1677 

31.97 

1839 

28.94 

3516 


30.31 


The  following  table  shows  the  mortality,  according  to  sex,  of  1000 
consecutive  cases  of  diphtheria  observed  by  Lennox  Browne: 


Sex.  Admitted.  Died. 

Males  .        .        . 533  162 

Females 467  121 

1000  283 


1  Lennox  Browue.    Loc.  eit. 


682 


DIPHTHERIA 


The  following  table  shows  the  mortality,  according  to  sex,  of  all 
cases  of  diphtheria  treated  in  the  Municipal  Hospital,  Philadelphia, 
from  1893  to  1902,  inclusive: 


Males 

Females. 

Year. 

Admitted. 

Died. 

Per  cent. 

Admitted. 

Died. 

Per  cent. 

1893     . 

.      94 

29 

30.85 

123 

33 

26.82 

1894     . 

.     214 

81 

37.85 

251 

73 

29.08 

1895     . 

.    315 

83 

26.4 

391 

107 

27.3 

1896     . 

.     424 

100 

23.58 

445 

90 

20.22 

1897     . 

.     636 

147 

23.11 

659 

153 

23.21 

1898     . 

.     562 

152 

27.04 

667 

145 

21.73 

1899     . 

.     641 

139 

21.68 

732 

136 

18.57 

1900     . 

.     669 

151 

22.56 

698 

147 

21.06 

1901     . 

.    416 

94 

22.59 

473 

80 

16.91 

1902     . 

.     285 

64 

22.45 

316 

73 

23. 10 

4256 


1040 


24.43 


4755 


21.8 


Race. — Race  seems  to  exert  no  influence  over  the  death  rate  from 
diphtheria.  At  least  this  is  true  in  regard  to  the  white  and  colored 
patients.  Some  observers  believe  that  the  blacks  are  more  liable  to  perish 
from  the  disease  than  the  whites,  but  this  is  not  in  accordance  with 
our  experience,  as  the  following  table  shows: 


White. 


Black. 


Year.          Admitted. 

Died. 

Per  cent. 

Admitted. 

Died. 

Per  cent 

1893 

208 

60 

28.84 

9 

2 

22.22 

1894 

434 

144 

33.18 

31 

10 

32.26 

1895 

660 

178 

26.9 

46 

12 

26.00 

1896 

838 

183 

21.83 

31 

7 

22.58 

1897 

1217 

281 

23.08 

78 

19 

24.35 

1898 

1177 

289 

24.55 

52 

8 

15.35 

1899 

1304 

262 

20.09 

69 

13 

18.84 

1900 

1309 

286 

21.84 

58 

12 

20.68 

1901 

843 

163 

19.33 

46 

11 

23.91 

1902 

567 

129 

22.75 

34 

8 

23.52 

8557 


1975 


23,08 


102 


While  it  is  impossible  to  predict  at  the  onset  of  diphtheria  the  ending 
of  any  case,  yet  it  may  be  said  that  when  the  inflammation  of  the  fauces 
is  mild  and  the  pseudomembrane  not  extensive,  with  but  moderate 
swelling  of  the  lymphatic  glands  of  the  neck,  the  termination  is  usually 
favorable.  When  the  exudation  is  limited  to  the  tonsils  the  danger  is 
not  great;  the  vast  majority  of  such  cases  recover  without  any  untoward 
after-effects.  On  the  other  hand,  if  the  inflamed  surface  be  extensive, 
the  pseudomembrane  copious,  the  exhalations  ofl^ensive,  and  the  neigh- 
boring lymphatic  glands  and  the  adjacent  tissue  very  much  swollen, 
the  patient's  condition  becomes  perilous.  It  may  be  safely  asserted 
that  the  danger  is  increasingly  grave  in  proportion  to  the  extent  of 
surface  involved  and  the  copiousness  of  the  exudation.  The  parts 
implicated  in  the  diphtheritic  process  must  also  be  taken  into  account 
in  forming  a  prognosis.  In  Lennox  Browne's  analysis  of  1000  cases  of 
the  disease,  the  mortality,  according  to  the  site  of  the  exudate,  was 
found  to  be  as  follows: 


DuathH. 

Per  cent. 

81 

12,1<5 

1 

25.00 

1 

50.00 

51 

45.53 

106 

64.24 

30 

61.22 

2 

33.83 

11 

01.06 

TTJE  PROGNOSIS  OF  1)1 1'llTII I'llil A  083 

Site  of  iiioinhraiic.  (/'aBCH. 

FauceH  (alone) 666 

Larynx      "             4 

Naros         "            2 

Fauces  and  larynx 112 

"         "      narea 165 

"        larynx,  and  naros 49 

Membrane  involviiiB  the  buccal  cavity  and  IIijh       6 
Membrane  involvhifi;  the  hard  palate        .        .      12 

If  the  fauces  alone  are  involved  the  patient  has  a  fair  chance  of 
surviving  the  attack.  Ikit  v\'here  the  exudate  forms  in  a  thick  mass 
on  the  hard  and  soft  palates  the  danger  becomes  imminent.  Some- 
times, however,  the  membrane  peels  off  quickly,  leaving  the  parts  quite 
free  from  ulceration,  and  recovery  speedily  follows,  although  paralysis, 
more  or  less  marked,  of  the  palatine  muscles,  is  rarely  absent.  The 
chief  source  of  danger  in  such  cases  is  from  the  absorption  of  the  tcjxins, 
giving  rise  to  toxajmia  and  heart-failure. 

When  the  nares  are  involved  the  prognosis  should  always  be  guarded. 
Very  many  if  not  the  majority  of  the  milder  cases  of  nasal  diphtheria 
recover,  and  also  some  of  the  severe  ones.  But  it  is  not  often  that  the 
disease  is  limited  to  the  nares.  If  the  nasal  cavities  show  distinct  plugs 
of  exudate  in  conjunction  with  marked  faucial  involvement,  as  is  usually 
the  case,  the  child's  condition  should  be  viewed  with  grave  apprehension. 
The  foregoing  table  shows  that  the  mortality  from  faucial  and  nasal 
diphtheria  was  as  high  as  64.24  per  cent. 

In  the  severe  cases  of  diphtheria  nasal  involvement  is  commonly 
present.  As  the  capillary  bloodvessels  are  very  superficial  in  the  cavities 
of  the  nose,  the  slightest  congestion  or  ulceration  of  the  mucous  mem- 
brane of  this  part  is  liable  to  give  rise  to  troublesome  hemorrhage. 
This  of  itself  is  .sometimes  a  source  of  danger.  But  the  greatest  danger 
is  from  systemic  poisoning,  which  is  extremely  liable  to  occur,  since 
the  lymphatics,  which  are  very  numerous  in  the  submucous  connective 
tissue  of  the  nostrils,  take  up  the  toxins  and  convey  them  to  every  part 
of  the  system.  This  condition  always  involves  great  danger  of  death 
by  asthenia,  due  to  toxpemia  and  heart -failure.  If  recovery  takes  place, 
more  or  less  paralysis,  local  or  general,  is  quite  sure  to  develop  during 
convalescence. 

The  occurrence  of  middle-ear  disease  as  the  result  of  diphtheria  is 
deemed  of  sufficient  importance  to  warrant  prognostic  consideration. 
It  is  believed  that  the  diphtheritic  process  not  infrequently  extends 
from  the  postnasal  space  through  the  Eustachian  tube  to  the  middle 
ear.  The  aural  involvement  may  impair  the  hearing,  but  only  in  rare 
instances  does  it  result  in  deafness.  likewise,  in  severe  nasal  diph- 
theria the  infection  may  be  conveyed  through  the  cribriform  plate  to 
the  brain,  causing  meningitis.  In  analyzing  liis  1000  cases  of  diphtheria, 
Lennox  Browne  says:  "It  may  also  here  be  mentioned  that,  in  one  case 
of  nasal  diphtheria,  death  ensued  from  meningitis,  and  no  aural  coni- 
plication  was  to  be  found.  This  circumstance  offers  a  not  improbable 
explanation  of  the  gravity  of  nasal  diphtheria.     For,  not  only  do  the 


684  DIPHTHEHIA 

turbinals  constitute  an  extensive  and  readily  absorbent  surface,  but 
there  is  a  liability  to  direct  cerebral  infection  through  the  cribriform 
plate,  as  has  been  observed  in  regard  to  cerebrospinal  meningitis  in 
which  the  specific  organisms  have  been  found  in  the  anterior  meninges." 

On  the  first ,  or  second  day  of  diphtheria  there  is  but  little  to  be 
learned  from  the  subjective  syiaptoms  that  is  of  prognostic  value.  A 
little  later,  in  the  graver  forms  of  the  disease,  one  may  often  see  in  the 
facial  expression  of  the  patient  something  indicating  the  serious  nature 
of  the  malady  that  presents  itself  for  treatment.  This  appearance  has 
been  characterized  as  a  "peculiar  facial  cachexia."  The  face  is  pale 
and  sallow,  often  puffy,  bloated,  or  slightly  oedematous;  the  skin  is 
smooth  and  shiny,  a  mucopurulent  discharge  issues  from  the  nostrils, 
the  facial  outline  is  somewhat  changed  by  the  swelling  of  the  neck, 
the  eyes  are  clear  and  bright,  but  the  expression  is  often  that  of  indolence 
and  apathy.  When  the  attack  is  likely  to  prove  fatal  the  face  becomes 
livid  or  of  a  dusky,  pallid  hue ;  in  case  of  nasal  involvement  blood  may 
either  ooze  or  flow  freely  from  the  nares,  and,  in  malignant  cases, 
petechiae  or  ecchymoses  may  appear,  not  only  on  the  face,  but  also  on 
other  parts  of  the  cutaneous  surface.  Altogether  the  facial  expression 
is  that  of  profound  blood  poisoning,  and  death  may  be  expected  at 
any  moment. 

Only  in  the  mildest  forms  of  toxaemia  is  recovery  possible.  When 
the  patient  suddenly  becomes  extremely  pale,  vomits  everything  that 
is  swallowed,  and  the  first  sound  of  the  heart  is  found  to  be  diminished 
in  intensity  or  absent,  and  the  pulse  becomes  feeble,  slow,  and  irregular, 
or  disappears  entirely  at  the  wrist,  the  fatal  end  is  not  far  off.  Often 
the  little  patient  will  utter  a  shriek,  as  if  suffering  from  pain,  and  place 
his  hand  over  the  precordial  region  just  as  he  is  about  to  expire.  In 
these  cases  death  results  from  asthenia  or  heart-failure,  due  to  profound 
systemic  intoxication.  W^hen  diphtheria  terminates  in  this  manner,  it 
is  usually  in  the  second  week  of  the  illness. 

Temperature. — The  prognostic  significance  of  the  temperature  has 
been,  v/e  think,  overrated  by  most  writers.  With  Lennox  Browne  we 
feel  that  "One  is  so  accustomed  to  read  and  hear  of  the  fever  of  diph- 
theria that  we  almost  hesitate  to  declare  our  conviction — formed  on 
personal  observation  and  confirmed  by  others  whose  experience  is 
much  greater — that  as  regards  fever  there  is  little  to  speak  of  as  com- 
pared with  the  acuteness  of  the  constitutional  disturbance  characteristic 
of  the  disease." 

If  the  temperature  continues  high  after  the  first  few  days  of  the 
illness  it  is  most  probably  due  to  the  development  of  some  complication. 
In  the  worst  cases  of  diphtheria  the  temperature  soon  falls  to  near  the 
normal  point,  and,  as  the  disease  progresses,  often  becomes  subnormal. 
With  the  other  symptoms  of  toxaemia  present,  the  occurrence  of  algidity 
should  be  regarded  as  a  fatal  omen,  as  it  indicates  the  approach  of 
death  by  asthenia.  In  septic  cases  the  temperature  may  continue  high, 
or  it  may  fluctuate  as  in  most  other  septic  conditions,  l^'his  can  readily 
be  explained  by  the  inflammation  of  the  lymphatic  glands  of  the  neck 


Tiii<:  ru.()(;N()Sis  or  i>ii'irriii:in.\  085 

which  always  accompanies  this  form  of  tlic  fliscasc.  'J'hc  })rognosis  in 
this  variety  of  (h'phtlieria  should  \m'.  exceedingly  quarried. 

Pulse.--  By  carefully  studying  the  pulse  from  time  t(;  time  one  may 
sometimes  acfjuire  information  of  considerabht  prognostic  value.  So 
long  as  the  j)ulse  is  not  too  rapid,  remains  regular  and  of  normal  volume, 
the  case  is  j)rol)al)ly  progressing  favorahly.  I^ut  when  it  hecfjines  very 
rapid  and  fe(>l)le,  or  slow  and  irregular,  our  gravest  apprehensions  should 
be  aroused.  The  ])ulse  rate  as  well  as  its  volume  is  influeneed  nif)re  l)y 
the  absorbed  toxins  than  by  the  pyrexia. 

A  ra])id  j)ulse  within  certain  limits  is  not  necessarily  unfavorable  so 
long  as  it  remains  regular.  But  if  it  constantly  grows  more  and  more 
rapid,  and  becomes  irregular  in  its  rhythm  and  force,  the  prognosis  is 
proportionately  bad.  If,  with  a  frequent  and  compressible,  or  a  slow 
and  intermittent  pulse,  there  is  also  subnormal  temperature,  a  pale, 
puffy,  apathetic,  and  cachectic  face,  the  prognosis  becomes  most  grave. 
In  speaking  of  the  prognostic  value  of  the  pulse  in  diphtheria,  Sir 
William  Jenner  says:  "An  extremely  rapid  and  feeble  pulse  is  of  grave 
import;  a  very  infrequent  pulse  is  of  fatal  significance." 

This  disturbance  of  the  circulatory  system  means  that  the  heart's 
function  is  affected  by  the  action  of  the  toxin  on  the  carrliac  nerves, 
and  possibly  also  that  the  myocardium  is  undergoing  some  change 
through  the  influence  of  the  poison.  When  the  heart's  action  becomes 
slow  and  weak  there  is  danger  of  clots  forming  in  the  ventricles  or  in 
the  large  bloodvessels  connecting  with  the  heart. 

One  of  the  special  dangers  to  be  feared  in  diphtheria  is  iuAolvement 
of  the  larynx,  giving  rise  to  membranous  croup.  The  disease  may 
occur  primarily  in  the  larynx,  but  more  often  it  begins  in  the  fauces 
and  extends  into  the  larynx.  The  patient  cannot  be  considered  free 
from  danger  of  the  pseudomembrane  extending  into  this  part  so  long 
as  the  disease  continues,  but  the  liability  of  such  an  occurrence  pro- 
gressively diminishes  after  the  first  week. 

The  danger  in  membranous  croup  is  twofold:  first,  from  laryngeal 
obstruction,  causing  suffocation  and  death;  and,  secondly,  from  bron- 
chitis or  bronchopneumonia.  Much  may  be  done  toward  overcoming 
the  first  source  of  danger  by  operative  measures,  but  even  then  the 
diphtheritic  inflammation  too  often  extends  downward  into  the  trachea, 
bronchi,  and  bronchioles,  and  not  infrequently  into  the  alveoli  of  the 
lungs,  giving  rise  to  bronchopneumonia.  We  believe  that  about  one- 
half  of  the  deaths  we  have  seen  in  membranous  croup  resulted  from 
the  latter  complication. 

The  prognosis  may  be  favorably  influenced  to  a  considerable  extent 
by  promptitude  in  employing  such  measures  as  intubation  or  trache- 
otomy for  relief  of  the  laryngeal  stenosis.  If,  after  either  of  these  pro- 
cedures, the  child  continues  to  breathe  easily  and  noiselessly,  sleeps 
quietly,  takes  nourishment  well,  runs  a  temperature  of  not  more  than 
one  or  two  degrees  above  normal,  and  has  a  good  color,  the  chances 
of  recovery  are  favorable.  On  the  other  hand,  if  the  respirations  are 
uneasy  and  noisy,  the  temperature  continues  high,  a  troublesome  cough 


686  DIPHTHERIA 

with  rales  throughout  the  lungs  appear,  and  the  color  of  the  patient 
shows  that  the  blood  is  not  properly  decarbonized,  the  chances  of 
recovery  are  slim. 

Membranous  croup  is  much  less  liable  to  be  attended  by  toxaemia  or 
followed  by  general  paralysis  than  are  most  other  forms  of  diphtheria. 
But  these  affections  may  occur  in  cases  of  membranous  croup  as  the  result 
of  involvement  of  the  fauces  or  nares  synchronously  with  the  larynx. 

Renal  Complication.^ — Renal  complication  is  not  often  of  much 
prognostic  importance.  The  slight  amount  of  albumin  that  is  fre- 
quently present  in  the  urine  is  of  no  great  significance,  provided  that 
granular  and  hyaline  casts  are  absent.  But  when  these,  together  with 
a  large  amount  of  albumin,  are  found,  and  the  amount  of  urine  excreted 
is  greatly  diminished,  the  outlook  is  not  encouraging.  If  suppression 
of  the  urine  occurs,  death  from  convulsions  and  coma,  as  the  result  of 
ursemic  poisoning,  would  soon  follow  if  relief  were  not  promptly  afforded. 
In  our  experience  such  a  termination  in  diphtheria  is  rare. 

The  prognosis  of  diphtheria  should  be  greatly  qualified  when  it 
occurs  coincidently  with  or  as  a  sequel  to  some  other  infectious  disease, 
like  scarlet  fever  or  measles.  In  patients  suffering  from  the  latter  disease 
diphtheria  seems  especially  liable  to  assume  the  form  of  membranous 
croup,  probably  because  of  the  catarrhal  affection  of  the  larynx  usually 
present  in  measles.  In  the  year  1900,  measles  of  a  malignant  type 
broke  out  in  the  diphtheria  wards  of  the  Municipal  Hospital,  Phil- 
adelphia, and  the  mortality  assumed  unduly  grave  proportions.  Of 
68  cases  of  diphtheria  complicated  with  measles,  34  died,  a  death  rate 
of  50  per  cent.  Indeed,  any  independent  affection,  however  mild 
ordinarily,  supervening  on  an  attack  of  diphtheria  may  become  inordi- 
nately severe  in  consequence  of  the  changed  condition  of  the  blood 
and  nervous  system  of  the  patient. 

Diphtheritic  Paralysis.— The  danger  from  diphtheritic  paralysis 
depends  very  much  on  the  parts  involved.  So  long  as  the  vital  organs 
of  the  body  remain  unaffected  the  prognosis  is  not  unfavorable.  Par- 
alysis of  the  soft  palate,  however  inconvenient  it  may  be  to  the  patient, 
is  not  fatal.  Likewise,  in  the  average  case  of  multiple  paralysis  recovery 
may  be  expected.  Even  in  the  more  extreme  cases,  if  the  heart's  function 
and  the  respirations  are  not  affected,  the  chances  of  recovery  are  fair, 
provided  the  patient  receives  proper  attention  during  the  critical  period. 
When  deglutition  is  impossible,  life  may  be  preserved  by  feeding  the 
child  through  an  oesophageal  tube.  Cardiac  paralysis,  which  is  most  to 
be  feared,  often  develops  suddenly  and  gives  rise  to  dangerous  symptoms 
of  heart-failure.    It  is  liable  to  occur  either  early  or  late  in  the  disease. 

We  have  already  mentioned  the  fact  that  multiple  paralysis  does  not 
make  its  appearance  until  the  fourth  to  the  sixth  week  of  the  illness. 
This  complication,  as  well  as  some  others  to  which  attention  has  been 
called,  tends  to  keep  the  patient's  life  in  danger  for  a  long  time.  Even 
when  a  well-marked  case  of  diphtheria  is  progressing  favorably,  it  is 
not  too  much  to  say  that  the  danger  period  is  not  passed  until  at  least 
six  weeks  have  elapsed  since  the  beginning  of  the  attack. 


CIT  APTER    XI  1  r. 

DIPHTHERIA  (Continued). 
THE  TREATMENT  OF  DIPHTHERIA. 

Since  antitoxin  has  achieved  for  itself  so  much  credit  as  an  immun- 
izing agent  against  diphtheria,  it  would  seem  that  it  deserves  first  place 
among  the  prophylactic  measures  to  be  considered.  So  important, 
indeed,  is  the  question  of  serum  treatment,  not  only  with  reference  to 
its  power  of  preventing  but  also  of  curing  the  disease,  that  we  have 
concluded  to  devote  a  special  chapter  to  the  subject.  We  find  it  most 
convenient,  however,  to  consider  the  question  of  treatment  of  diphtheria 
in  the  following  order:  first,  the  hygienic  or  preventive  treatment; 
second,  the  medicinal  treatment;  third,  the  specific  or  serum  treatment. 

Preventive  Treatment. — As  soon  as  the  nature  of  the  disease  is  known 
the  patient  should  be  separated  as  far  as  possible  from  the  other  members 
of  the  household.  This  is  important  even  when  the  attack  is  ever  so 
mild,  as  severe  cases  may  result  from  mild  ones.  If  the  patient  is  to 
be  treated  at  home  the  other  children,  if  there  be  any,  should  receive 
an  immunizing  dose  of  antitoxin  and  should  be  immediately  sent 
out  of  the  house.  If  this  is  not  feasible,  they  should  be  excluded 
from  the  sick-chamber  and  assigned  to  bed-rooms  in  the  most  distant 
part  of  the  dwelling.  Their  hygienic  conditon  should  be  looked  after; 
at  least  they  should  be  properly  fed,  regularly  bathed,  and  provided 
with  plenty  of  fresh  air  day  and  night.  Their  throats  and  nostrils 
should  be  examined  every  day,  and  as  soon  as  anything  abnormal  is 
discovered  the  child  should  be  immediately  separated  from  the  others 
and  given  suitable  treatment. 

One  of  the  uppermost  rooms  in  the  house  should  be  selected  for 
the  patient.  It  should  be  light  and  properly  heated,  and  pronded  with 
facilities  for  obtaining  ventilation  without  incurring  the  risk  from 
draughts.  An  open  fire-place,  with  at  least  a  little  fire  burning,  is  a 
very  desirable  aid  toward  maintaining  the  purity  of  the  air  in  the  room. 
The  most  suitable  temperature  is  70°  to  72°  F.  All  unnecessary  hang- 
ings, furniture,  and  the  like,  that  are  liable  to  retain  the  contagium, 
should  be  removed  from  the  chamber.  In  the  winter  months,  when  the 
heated  air  of  the  room  is  usually  dry,  it  may  be  moistened  by  steam, 
which,  if  deemed  advisable,  may  be  slightly  impregnated  with  eucalx-ptol, 
or  some  other  fragrant  essential  oil.  This  is  more  especially  advisable 
when  the  patient  manifests  croupy  s}^Ilptoms. 

If  more  than  one  member  of  the  family  be  ill  with  the  disease,  care 
should  be  taken  not  to  overcrowd  the  patients.     Each  patient  should 


688  DIPHTHERIA 

be  allowed  at  least  2000  cubic  feet  of  air  space,  with  an  additional 
allowance  for  the  nurse.  The  nurse  should  be  instructed  to  keep  the 
patients  as  quiet  as  possible;  at  least,  so  far  as  active  bodily  movements 
are  concerned.  When  the  heart  is  found  to  be  weak,  she  should  feed 
the  patient  by  means  of  a  feeding  cup,  and  not  allow  him  to  rise  or  get 
out  of  bed  under  any  circumstance  whatever. 

During  the  illness  of  the  patient  the  privileges  of  the  well  members 
of  the  household  should  be  restricted.  They  should  be  advised  not  to 
attend  church  nor  public  assemblages  of  any  kind.  The  children,  if 
there  be  any,  should  at  once  be  required  to  leave  school,  and  should  not 
be  readmitted  until  the  family  physician  or  some  qualified  sanitary 
officer  certifies  that  the  sickness  has  ended,  and  that  the  house  has  been 
thoroughly  cleansed  and  disinfected.  The  isolation  of  the  patient 
should  continue  until  the  diphtheritic  exudate  has  disappeared,  and  the 
affected  mucous  membrane  has  become  entirely  normal.  When  possible, 
cultures  should  be  made  to  determine  the  absence  of  the  specific  bacilli; 
if  two  successively  negative  cultures  be  obtained  it  may  be  considered 
safe  to  allow  the  patient  to  associate  with  the  other  members  of  the 
family,  provided  he  has  had  an  antiseptic  bath  and  is  dressed  in  clean 
clothing. 

As  the  infecting  principle  of  the  disease  clings  to  articles  which  have 
been  used  by  the  patient,  or  which  have  been  in  the  same  apartment, 
all  such  articles  as  are  worthless  should  at  once  be  burned.  Only  such 
books,  toys,  and  the  like,  as  may  be  burned  at  the  termination  of  the 
illness  should  be  allowed  in  the  sick-chamber.  All  articles  for  the 
laundry  should  be  steeped  for  some  time  in  a  disinfecting  solution,  such 
as  two  fluidounces  of  chloride  of  zinc,  or  four  fluidounces  of  strong 
carbolic  acid,  to  a  gallon  of  water,  and  afterward  boiled  for  half  an  hour. 
For  the  disinfection  of  woollen  goods  formalin  may  be  used,  but  for 
efficiency  there  is  nothing  that  ecjuals  superheated  steam.  All  utensils 
used  by  the  patient  in  eating  or  drinldng  should  be  purified  each  time 
by  means  of  boiling  water.  The  secretions  from  the  patient's  mouth 
and  nose  should  be  disinfected  by  receiving  them  into  a  strong  solution 
of  chloride  of  lime,  or  a  mercuric  chloride  solution  (1 :  1000),  or  some 
other  equally  powerful  gerrn-destroying  agent.  Small  pieces  of  worn 
cotton  goods,  or  cheesecloth,  may  be  used  to  receive  such  secretions, 
and  should  be  destroyed  at  once  by  fire. 

T'he  nurse  or  any  other  attendant  should  wear  clothing  made  of  such 
material  as  can  be  readily  boiled  and  laundered.  Before  associating 
with  well  persons  she  should  take  an  antiseptic  bath,  washing  her  hair 
at  the  same  time,  and  change  her  entire  clothing.  The  physician  also, 
should  exercise  care  lest  he  himself  may  be  the  means  of  conveying  the 
infection  to  others.  He  should  not  remain  in  the  sick-chamber  longer 
than  is  necessary  to  make  a  proper  examination  of  the  patient.  Before 
leaving  the  house  he  should  take  the  precaution  to  wash  his  face,  hair, 
and  hands;  the  latter  should  be  held  for  a  few  moments  in  some  anti- 
septic solution,  as  inercuric  chloride,  1 :  1000.  He  should  delay  visiting 
another  patient  until  he  has  spent  some  time  in  the  open  air,  or,  what 


77//';  tr,i<:atmI':nt  of  dii'ii'iiiI'IHIA  680 

is  better,  chaiif^ed  his  clothing.  It  is  (icsirahle  for  liini  to  w^-ar  in  the 
room  a  long  rubber  coat  or  Wuv.n  gown,  which  shoiiM  b<-  kept  hanging 
in  i\\v  o[)('n  air  (hiring  th(;  interval  of  In's  visits. 

As  the  body  of  a  patient  who  has  died  of  diphtheria  is  slill  eajKiljle 
of  transmitting  the  contagium,  certain  j)reeaiitions  in  regard  to  it  are 
necessary.  An  effort  should  be  made  to  disinf(;ct  th(!  body  by  thf)roughly 
washing  it  with  some  powerful  disinfecting  solution.  Ther(!  is  jx-rhaps 
nothing  more  relial)le  than  chloride  of  lime.  Six  ounces  of  tin's  <lrug 
to  a  gallon  of  water  nuikes  a  very  effective  germicide.  The  body  should 
be  wrapped  in  a  sheet  saturated  with  this  or  some  other  similar  solution 
before  it  is  placed  in  the  hermetically  sealed  casket,  and  the  burial 
should  follow  as  speedily  as  possible,  without,  of  course,  a  })ublic  funeral. 

When  the  illness  has  terminated,  either  by  recovery  or  death  r)f  the 
patient,  the  sick-chaml)er  and  every  article  it  contains  should  be  thor- 
oughly disinfected.  This  may  be  accomplished  by  using  formalin 
according  to  the  directions  given  in  the  article  on  disinfection,  or  by 
burning  in  the  room  three  to  five  pounds  of  sulphur  to  every  1000  cubic 
feet  of  air  space,  the  room  ha^■ing  first  been  made  as  nearly  air-tight  as 
possible.     (See  chapter  on  Disinfection.) 

As  already  indicated,  all  washable  goods  in  the  room  of  the  patient 
should  be  immersed  in  boiling  water  for  half  an  hour,  and  then 
laundered.  Woollen  clothing,  mattresses,  pillows,  carpets,  and  all  other 
articles  which  cannot  be  laundered,  should  be  so  arranged  in  a  room 
as  to  be  thoroughly  exposed  to  the  influence  of  the  formaldehyde 
vapor  or  the  sulphur  dioxide.  When  feasible,  such  articles  as  those 
last  named  should  preferably  be  sent  to  a  disinfecting  station  and 
exposed  to  superheated  steam  under  pressure  for  thirty  minutes.  All 
picture-books,  toys,  and  other  things  sent  in  for  the  amusement  of  the 
patient  should  be  burned.  After  the  room  has  been  disinfected,  cleansed, 
and  the  paper  on  the  wall  changed,  it  should  be  thoroughly  aired,  and, 
if  possible,  remain  unoccupied  for  a  few  days. 

As  some  of  these  requirements  would  be  only  indifferently  carried 
out  by  the  average  citizen,  the  local  sanitary  boards  should  have  authority 
to  exercise  supervision  over  dwellings  in  which  diphtheria  makes  its 
appearance,  and  should  be  provided  with  the  necessary  means  and 
facilities  for  eradicating  the  infection.  The  work  of  disinfection  should 
always  be  conducted  by  a  properly  qualified  sanitary  officer,  and,  as  it 
is  done  in  furtherance  of  public  safety,  the  public  treasury  should  supply 
the  means.  In  every  large  city  a  suitable  disinfecting  station  should  be 
provided  for  purifying  without  cost  all  portable  articles,  particularly 
such  as  cannot  be  conveniently  or  properly  disinfected  at  home.  Phil- 
adelphia and  many  other  cities  of  this  country  are  provided  with  such 
facilities. 

In  order  to  afford  health  authorities  the  earliest  opportunity  to  apply 
any  or  all  of  the  measures  which  have  been  here  indicated  for  restrict- 
ing or  preventing  the  spread  of  diphtheria,  every  case  of  the  disease 
should  be  promptly  reported  as  soon  as  the  diagnosis  is  determined. 
In  some  municipalities  the  physician  in  attendance  on  a  patient  is 

44 


690  DIPHTHERIA 

required  to  give  such  notification — a  requirement  which,  we  think,  is 
not  unreasonable. 

Another  means  of  preventing  the  dissemination  of  diphtheria,  as 
well  as  other  dangerous  communicable  diseases,  is  to  apprise  the  public 
of  the  particular  house  in  which  it  is  present.  How  to  do  this  without 
exciting  opposition  is  a  problem  not  easy  of  solution.  The  means  adopted 
in  many  parts  of  this  country  is  to  affix,  in  a  conspicuous  place  at  the 
entrance  of  the  house,  a  placard  announcing  the  existence  of  diphtheria 
within.  While  this  is  usually  distasteful  to  the  householder,  it  serves 
the  purpose  of  preventing  any  one  from  incurring  danger  unwittingly. 
But  whether  this  plan  be  adopted  or  not,  the  sanitary  authorities  should 
keep  the  premises  under  supervision,  instituting  visits  from  time  to 
time  by  officers  qualified  and  empowered  to  advise  and  direct  the 
observance  of  proper  sanitary  precautions,  and,  if  there  be  danger  of 
non-compliance,  to  put  in  force  more  arbitrary  restrictive  measures. 

Besides  enforcing  the  preventive  and  restrictive  measures  which  have 
been  outlined,  antitoxin  should  be  administered  as  a  prophylactic  in 
households  in  which  diphtheria  has  made  its  appearance. 

Local  Treatment. — With  reference  to  the  therapeutic  indications  in 
diphtheria,  it  is  necessary  to  consider  both  the  local  and  constitutional 
manifestations  of  the  disease.  According  to  the  present  views  relating 
to  the  etiological  and  pathological  connection  between  the  local  affection 
and  the  systemic  condition,  it  is  obvious  that  local  treatment,  especially 
at  the  beginning  of  the  disease,  is  a  matter  of  great  importance.  If 
it  be  true,  as  we  believe,  that  the  disease  is  produced  by  certain  organisms 
which,  when  deposited  upon  the  mucous  membrane  of  the  throat  or 
nose,  will  commence  to  multiply,  if  the  soil  be  favorable,  and  elaborate 
a  peculiar  and  most  virulent  toxin  which  is  conveyed  by  the  blood 
to  all  parts  of  the  system,  it  is  reasonable  to  suppose  that  local  treatment 
should  prove  of  great  service. 

It  would  seem,  therefore,  that  it  should  be  the  prime  object  in  treat- 
ment to  destroy  those  organisms  as  early  and  as  quickly  as  possible. 
But  how  to  do  this  effectually  without  inflicting  injury  on  the  parts 
invaded  is  a  question  not  easy  of  solution. 

The  probability  of  the  correctness  of  this  view  has  prompted  many 
practitioners  to  make  use  of  heroic  local  treatment.  Such  caustic  and 
irritating  applications  to  the  throat  as  nitrate  of  silver,  sulphate  of 
copper,  and  strong  solutions  of  pernitrate  or  persulphate  of  iron  were 
formerly  much  in  vogue,  and  are  not  without  their  advocates  at  the 
present  day. 

Even  more  active  cauterants,  like  hydrochloric  acid  and  nitric  acid, 
have  been  employed  with  asserted  benefit.  Flint  speaks  of  a  medical 
friend  of  his  with  much  experience,  who  was  convinced  that  by  the 
prompt  and  thorough  application  of  nitric  acid,  if  the  part  primarily 
affected  can  be  seen  and  reached,  the  progress  of  the  disease  may  with 
certainty  be  arrested. 

Such  severe  local  measures  are  objected  to  on  the  ground  that  they 
impair  the  continuity  of  the  tissues,  and  thus  facilitate  the  entrance  into 


THE  TREATMENT  OF  DIPHTHERIA  691 

the  system  of  the  poisons  generaterl  In*  the  Kh'bs-I-oeffler  haciUi  and 
their  associates.  Impairment  of  the  tissues  also  facilitates  extension  of 
the  pseudomembrane,  for  it  is  well  known  that  the  mucous  membrane 
of  the  mouth,  if  not  intact,  is  liable  to  become  involved  in  tiie  diph- 
theritic process.  All  caustic  and  irritating  local  applications  are  there- 
fore to  be  condemned  as  being  more  harmful  than  Ix'neficial. 

In  place  of  the  cauterizing  lotions,  most  physicians  now  prefer  those 
which  are  supposed  to  have  more  especially  an  antiseptic  effect  on  the 
diphtheritic  exudate.  The  drugs  which  have  been  employed  for  this 
purpose  are  very  numerous.  Among  the  more  efficient  antiseptics  that 
have  been  recommended  may  be  mentioned  carbolic  acid,  permanganate 
of  potassium,  sulphite  of  soda,  subsulphate  of  iron,  l^enzoate  of  soda, 
chloral  hydrate,  and  chlorate  of  potassium.  These  have  l)een  used 
singly,  or  two  or  more  have  been  combined.  They  are  usually  applied 
in  a  liquid  form  by  means  of  a  cotton  swab,  a  camel's  hair  brush,  or 
the  hand  atomizer.  Good  results  have  followed  the  employment  at 
short  intervals  of  mild  antiseptic  applications.  Salicyhc  acid  is  said 
to  be  useful  when  applied  in  the  form  of  a  dry  powder  in  combination 
with  subnitrate  of  bismuth.  It  has  been  used  also  in  the  form  of  salicylate 
of  sodium  in  solution  (7  parts  to  100  of  water). 

Solution  of  chlorate  of  potassa  has  for  a  long  time  enjoyed  considerable 
reputation  as  a  gargle.  Oertel  ad\-ises  a  spray  of  chlorate  of  potassa 
and  salicyhc  acid  in  solution.  But.  he  says,  the  most  suitable  remedies 
to  meet  the  indication  of  opposing  septic  infection  and  general  poisoning 
of  the  system  are  alcohol,  freshly  prepared  and  properly  ililuted  chlorine- 
water  (the  gargle  containing  15  to  30  per  cent,  of  chlorine-water),  a 
solution  of  permanganate  of  potash  (1^  to  2^  grains  to  the  ounce  of 
water),  or  of  carbolic  acid  {2\  grains  to  the  ounce  of  water).  Where 
these  cannot  be  borne  he  recommends  a  solution  of  oil  of  th^Tue  in 
equal  parts  of  spirits  of  wine  and  water.  He  says:  "With  these  the 
patient  has  to  rinse  his  mouth  once  or  tAvice  at  least  every  hour,  or 
where  this  is  not  easily  possible,  as  in  the  case  of  small  children,  we 
must  seek  to  cleanse  the  mouth  and  throat  bv  the  use  of  the  svrin^e." 

Oertel  attaches  much  importance  to  his  recommendation  of  combining 
the  use  of  antiseptic  gargles  with  frequent  inhalations  of  hot  vapor. 
He  beUeves  that  by  thus  setting  up  a  rapid  and  abundant  suppuration 
the  separation  of  the  pseudomembrane  is  not  only  hastened,  but  that 
the  bacteria  are  partly  taken  up  by  the  rapidly  forming  pus  corpuscles, 
and  partly  washed  away  by  them  with  the  assistance  of  the  antiseptic 
mouth:  washes  and  gargles.  He  says:  "According  to  the  individual 
peculiarity  in  capacity  of  reaction  -will  this  separation  occur  more  or 
less  rapidly;  and  it  will  depend  upon  the  height  the  disease  has  alreadv 
reached  whether  the  septic  att'ection  and  general  poisoning  can  be 
prevented  and  how^  far  this  can  be  done." 

After  all,  it  must  be  admitted  that  gargles  are  of  questionable  utihtv. 
They  can  be  used  only  in  older  children  and  adults;  when  most  artfullv 
used  they  do  not  reach  much  beyond  the  oral  ca^-ity.  At  the  best  thev 
never  touch  amihing  beyond  the  anterior  pillars,  or  not  more  than  a 


G92  DIPHTHERIA 

small  part  of  the  tonsils.  In  severe  cases  gargles  are  objectionable, 
in  that  the  patient  is  required  to  rise  from  the  recumbent  position  when 
using  them.  They  are  to  be  recommended  only  at  the  beginning  of 
diphtheria,  or  where  the  disease  is  of  a  mild  character,  and  even  then 
their  use  must  he  limited  to  patients  old  enough  to  perform  the  act  of 
gargling.    _  _   . 

Applications  to  the  throat  may  be  made  most  conveniently  and 
efficiently  with  an  atomizer  or  a  syringe.  Lennox  Browne  had  specially 
designed  for  his  use  a  syringe  which  consists  of  two  tubes,  one  straight 
and  the  other  more  or  less  curved,  with  several  small  holes  at  the  end, 
and  attached  to  a  large  rubber  ball.  It  may  be  introduced  into  the 
mouth  behind  the  teeth,  or,  with  the  curved  tube,  back  into  the  post- 
nasal space  when  it  is  desirable  to  reach  the  pharyngeal  vault. 

His  choice  as  a  topical  remedy,  next  to  lactic  acid,  is  the  biniodide 
of  mercury,  for  the  reason  that  it  does  not  precipitate  the  serum  albumin 
as  does  the  bichloride.  He  advises  its  use  either  in  the  form  of  spray, 
or  douche  by  means  of  a  syringe,  in  a  strength  of  1 :  2000  to  5000  of 
water.  He  says  the  results  of  syringing  the  throat  with  a  solution  of 
bichloride  or  biniodide  of  mercury  are  certainly  excellent. 

This  author  recommends  the  following  formulae: 

LoTio  Hydrargyri  Biniodi. 

]9^ —Red  iodide  of  mercury gr.  5i. 

Iodide  of  sodium gr-  5i. 

Water fS  j.— M. 

Sig. — To  be  applied  by  a  swab  or  an  irrigating  syringe. 

LoTio  Hydrargyri  Bichloridi. 

9; —Bichloride  of  mercury gr.  3^. 

Water '.....    fS  j.— M. 

Sig. — For  application  by  a  swab  or  an  irrigating  syringe. 

Either  of  the  above  solutions  is  equal  to  1 :  2000,  and  may  be  still 
further  diluted  if  deemed  advisable.  As  it  is  probable  that  a  part  of 
the  lotion  will  be  swallowed,  we  recommend  that,  in  children,  a  much 
weaker  solution  be  used  (1:5000  to  10,000). 

In  the  employment  of  these  solutions,  as  well  as  most  others  that  are 
usually  recommended,  Lennox  Browne  advises  that  they  be  used  at  as 
high  a  temperature  as  can  be  borne,  as  thereby  their  microbicidal 
activity  is  increased.  He  also  calls  attention  to  the  fact  that  both  alcohol 
and  glycerin,  so  often  prescribed  in  combination  with  antiseptic  throat 
washes,  are  said  to  interfere  with  the  germ-destroying  properties  of 
both  mercury  and  carbolic  acid. 

Loeffler's  experience  with  certain  local  applications  in  diphtheria 
is  interesting,  both  from  a  practical  and  scientific  point  of  view.  Accord- 
ing to  Lennox  Browne,  "He  found  that  the  bacillus  of  diphtheria  may 
be  killed  in  twenty  seconds  by  perchloride  of  mercury,  chlorine-water, 
carbolic  acid,  or  a  solution  containing  turpentine  and  carbolic  acid 
But  it  not  being  always  practicable  to  keep  these  topical  applications 
in  contact  with  the  diphtherial  membranes  for  so  long  a  time,  he  endeav- 


77//';  TJil'JATMJ'JNT  OF  1)1 1'llTII ICIlIA  693 

ored  to  discover  other  substances  (;a[)al)l(!  of  more  quickly  destroying 
the  bacilhis.  In  the  course  of  his  researches  he  found  that  sesf|ui- 
chloride  of  iron,  dissolved  in  cfjual  j)arts  of  water,  or  in  tfie  proportion 
of  1  to  2,  as  well  as  other  j)reparations  of  iron,  kills  the  bacillus  with 
twice  the  rapidity.  Having  also  noticed  that  certain  essences,  such  as 
benzol  and  toluol,  int(;rfere  with  the  development  of  the  bacillus  of 
diphtheria,  he  investigat(>d  their  action  on  animals,  and  afterward  on 
man.  For  the  latter  purjxjse  Ix;  emj^loyed  a  mixture  containing  irc^n, 
toluol,  and  creolin  or  rnetacresol.  Finding,  however,  that  this  solution 
produced  a  marked  smarting  sensation  in  the  throats  of  children,  he 
added  to  it  menthol. 

"A  cotton  tampon  steeped  in  this  solution  is  apy^lied  to  the  affected 
parts  twice  in  succession  for  ten  seconds,  and  this  treatment  is  r(!peated 
every  three  hours,  until  all  the  local  symptoms  have  disappeared,  which 
ordinarily  occurs  within  four  or  five  days.  While  the  affection  is  still 
local,  it  may  be  arrested  in  its  course  by  this  solution;  bacteriological 
examination  will  show  that  all  the  bacilli  in  the  membranes  are  killed. 
Loeffler  reports  that  in  96  cases  treated  in  this  manner,  three-fourths 
of  which  were  shown  by  bacteriological  examination  to  be  true  diph- 
theria, not  a  single  death  occurred." 

Ijoeffler  recommends  two  solutions,  the  formulae  of  which  are  as 
follows : 

Loeffler's  Solution  (1). 

'!^ — Menthol 10  grams. 

Solve  in  toluol  ad 36  c.c. 

Alcohol,  abs 60  c.c. 

Liq.  ferri  sesquichlorid 4  c.c— Nf . 

Loeffler's  Solution  (2). 

Jk— Menthol 10  grams. 

Solve  in  toluol  ad 36  c.c. 

Alcohol,  abs 02  c.c. 

Creolin 2  c.c— M. 

Either  of  these  solutions  may  be  applied  with  a  cotton  swab  to  the 
diphtheritic  patches  every  three  or  four  hours  in  the  manner  mentioned 
above.  It  may  be  well  to  clear  the  throat  of  mucus  by  mopping  it  with 
cotton  before  making  the  application.  It  is  advised  that  the  applications 
be  made  a  little  more  frequently  in  bad  cases. 

We  have  not  used  these  solutions  extensively,  but  have  given  them 
a  fair  trial  without  obtaining  results  anything  like  as  favorable  as  those 
seen  by  Loeffler. 

Jacobi  says:  "Wlien  the  diphtheritic  pseudomembrane  is  within 
reach,  it  should  be  either  destroyed  or  disinfected.  For  that  purpose 
one  or  two  drops  of  a  50  per  cent,  solution  of  carbolic  acid  in  glycerin 
may  be  applied  once  (not  more  than  twice)  a  day,  or  of  the  tincture  of 
iodine,  or  of  a  solution  of  1  part  of  the  bichloride  of  mercury  in  100  or 
500  parts  of  water,  several  times  a  day."  But  he  calls  attention  to  the 
fact  that  only  a  small  part  of  the  pharjnax  is  accessible  to  such  treatment, 
and  that  it  is  possible  to  apply  it  to  only  a  small  class  of  patients.  He 
condemns  in  forcible  language  the  indiscriminate  use  of  strong  appli- 


694  DIPHTHERIA 

cations  to  the  throats  of  children.  He  says:  "Smaller  children  will 
object,  will  defend  themselves,  will  struggle.  It  takes  many  an  anxious 
moment  to  force  open  the  mouth;  meanwhile,  the  patient  is  struggling, 
perspiring,  screaming,  and  exhausting  his  strength.  One  may  succeed 
in  forcing  open  the  jaws,  then  there  begins  the  practice  of  making 
applications,  of  swabbing,  of  scratching  off  the  pseudomembrane,  of 
cauterizing,  of  burning.  The  struggling  child  will  prevent  the  limitation 
of  the  application  to  the  diseased  surface.  One  cannot  help  injuring 
the  neighboring  epithelium,  and  thus  the  morbid  process  will  spread. 
Instead  of  doing  good,  we  have  done  harm;  for,  indeed,  no  local  appli- 
cation can  do  so  much  good  as  the  struggles  of  the  frightened  children 
do  mischief.  I  have  seen  them  die  while  defending  themselves  against 
the  attempted  violence,  leaving  doctor  and  nurse  victorious  and  alive 
on  the  battle-field."  Jacobi  believes  that  a  very  good  local  effect  may 
be  produced  by  the  swallowing  of  medicines  which  are  at  the  same 
time  disinfectants,  digestible,  and  easy  to  take;  that  they  should  be 
given  in  small  doses  and  frequently  repeated.  Of  this  class  of  medicines 
he  mentions  tincture  of  the  chloride  of  iron,  lime-water,  solutions  of 
boric  acid,  bichloride  of  mercury,  or  benzoate  of  sodium. 

Solvents. — For  the  destruction  and  removal  of  the  pseudomem- 
brane, certain  agents  known  as  solvents  have  been  employed  from  time 
to  time.  Among  the  unirritating  solvents  may  be  mentioned  alkalies, 
pepsin,  trypsin,  and  papayotin.  The  agent  that  has  been  most  largely 
used  is,  perhaps,  lime-water,  or  steam  from  slaking  lime.  Its  solvent 
action,  if  it  has  any,  is  due  to  its  alkalinity,  which,  as  J.  Lewis  Smith 
says,  may  be  increased  by  adding  sodium  bicarbonate  to  it.  From 
observing  its  effects  in  a  considerable  number  of  cases,  this  author 
recommends  with  confidence  the  following  formula: 

P — 01.  eucalypti 5  ij. 

Sodii  benzoat. S  j. 

Sodii  bicarbonat .  3  ij. 

Glycerinse '      .        .  S  ij. 

Aqusecalcis Oj.— M. 

Sig. — To  be  used  witb  tbe  hand  atomizer  from  three  to  five  minutes  every 

half-hour,  or  with  the  steam  atomizer  almost  constantly. 

The  writer  says:  "This  alkaline  spray  not  only  exerts  a  solvent  action 
on  the  pseudomembrane,  but  also  renders  the  mucopus  thinner,  less 
viscid,  and,  therefore,  so  changes  its  character  by  diminishing  its  viscidity 
that  it  is  more  easily  expectorated." 

As  trypsin  is  an  active  solvent  in  an  alkaline  medium,  J.  I^ewis  Smith 
suggests  that  it  may  be  added  with  advantage  to  the  alkaline  mixture 
just  described.  Indeed,  this  writer  is  inclined  to  believe  that  such  a 
combination  forms  the  best  solvent  mixture  known.  The  pseudo- 
membrane has  been  seen  to  dissolve  and  disappear  quickly  under  the 
use  of  the  following  formula: 

]^— Trypsin gr.  xxx. 

Sodii  bicarb gr.  x. 

Aquse  destillat g  j. — M. 

Sig,— To  be  applied  frequently  with  the  hand  atomizer  or  a  cotton  swab. 


Tlll<:  TIINATMI'INT  Oh'  1)1 1'llTII hllU A  P,05 

Pepsin  has  hccu  used  as  a  .solvent,  with  varyini^  n-sults.  It  was 
recommended  in  di[)hth(M-ia  solely  on  tlieoretif;al  ^roniifls,  and  has 
proved  to  1)0  of  douhtful  utility. 

Some  writers  sp(!ak  favorably  of  pajmyotin.  in  s(;lution  as  a  solvent 
of  pseudomem})rane.  Among  these  may  he  mentioned  Ko.ssbach, 
J.  K.  l^auduy  (Jr.),  and  Jaeohi.  'l^'he  drug  is  said  to  he  readily  soluhle 
in  20  parts  of  water,  and  it  is  claimed  hy  Kosshach  that  if  a  few  minims 
be  placed  on  the  tongue  every  five  minutes  tlu;  membrane  will  dissolve 
in  two  or  three  hours.  Jacobi  has  u.sed  it  with  fair  results,  applying 
the  solution  with  a  swab  or  the  atomizer.  He  says  he  employed  the 
drug  many  years  ago  in  greater  concentration  to  dissolve,  after  trache- 
otomy, the  diphtheritic  meml)rane  in  the  trachea  below  the  tracheal 
tube. 

As  already  intimated,  Lennox  Browne  gives  lactic  acid  first  place 
among  the  local  applications.  He  believes  its  efficiency  is  due  in  a 
measure  to  the  fact  that  an  acid  medium  is  inimical  to  the  V)acillus,  Vjut 
that  its  greatest  merit  is  its  power  to  disintegrate  or  digest  false  mem- 
brane. He  makes  this  strong  statement:  "Truth  to  say,  we  have  been 
so  well  satisfied  with  lactic  acid  that  we  have  been  loath  to  try  any  other 
local  remedy.  We  have  not  found  it  injurious  to  contiguous  healthy 
tissue — that  is  to  say,  wherever  the  epithelial  layer  is  entire.  Its  action 
appears  to  be  limited  almost  solely  to  unhealthy  tissue,  promoting  its 
disintegration  by  a  process  analogous  to  that  of  digestion;  there  is,  it 
is  true,  some  circumferential  inflammation,  but  as  this  is  only  of  the 
degree  of  healthy  reaction  and  leads  to  the  outpouring  of  scavenging 
leukocytes,  it  is  to  be  regarded  as  a  desirable  result." 

This  author  advises  that  the  lactic  acid  be  applied  pure,  or  rather  of 
(British)  pharmacopoeial  strength,  by  the  physician  at  least  once  or 
twice  a  day,  and  that  the  drug,  moderately  diluted,  be  applied  by  the 
nurse  every  three  or  four  hours  until  the  membrane  has  disappeared. 
The  following  formula  is  recommended: 

]^— Lactic  acid  (P.  B.) 1  part. 

Distilled  water 3  parts. — M. 

Sig.— To  be  applied  by  the  nurse  or  attendant  every  three  or  four  hours  with 

a  cotton  swab  or  the  hand  atomizer. 

Our  experience  with  the  so-called  solvents  in  diphtheria  has  led  us  to 
believe  that  they  are  not  to  be  depended  upon.  They  may  act  very 
well  in  the  test-tube,  but  their  digestive  and  solvent  action  is  too  feeble 
to  be  of  much  practical  value  during  the  short  time  that  it  is  possible 
for  them  to  remain  in  contact  with  the  pseudomembrane  in  the  throat. 
^Vhile  the  antiseptic  mouth  washes,  gargles,  and  sprays  are  useful  to 
a  limited  extent,  yet  their  action  is  too  feeble  and  intermittent  to  be  of 
any  great  practical  value.  We  have  already  expressed  our  disapproba- 
tion of  caustic  applications,  and  we  agree  with  those  who  believe  that 
nothing  is  to  be  expected  from  mere  astringents,  ^^^len  we  consider 
that  the  purpose  or  design  of  local  treatment  is  the  prevention  of 
extension  of  the  pseudomembrane,  promotion  of  its  separation,  destruc- 
tion of  the  bacilli,  and  the  prevention  of  toxic  absorption,  we  must 


696  DIPHTHERIA 

admit  that  of  the  various  remedies  recommended,  some  of  which  even 
vaunted  as  specifics,  no  one  has  stood  the  test  of  experience. 

We  would  not  be  understood  as  discouraging  local  applications  in 
diphtheria;  on  the  contrary,  we  believe  that  when  used  with  good 
judgment  they  may  be  of  great  service.  We  have  but  little  confidence, 
however,  in  their  power  to  accomplish  to  any  marked  degree  the  purposes 
mentioned  above,  although  as  cleansing  agents  they  are  very  useful. 
Any  unirritating  antiseptic  solution  may  be  employed,  but,  after  all, 
quite  as  much  may  be  accomplished  with  a  warm  normal  salt  solution. 
It  should  be  the  aim  of  the  physician  to  keep  the  parts  involved  as  clean 
as  possible  without  taxing  too  much  the  strength  of  the  patient.  This 
may  be  best  accomplished  by  irrigation,  either  with  a  syringe  similar 
to  the  one  devised  by  Lennox  Browne,  or  with  the  ordinary  fountain 
syringe.  Swabs  should  not  be  used,  except  by  the  physician  or  trained 
nurse,  and  then  only  with  great  care. 

At  the  very  beginning  of  diphtheria,  or  even  when  the  disease  is 
simply  suspected,  the  throat  should  be  sprayed  every  hour,  at  least 
for  a  few  hours  in  succession,  with  a  mild  and  unirritating  antiseptic 
solution,  such  as  a  1  per  cent,  boric  acid  solution,  diluted  Dobell's 
solution,  hydrogen  peroxide  with  equal  parts  of  water,  or  a  solution  of 
1 :  4000  or  6000  of  bichloride  of  mercury.  Twenty-four  hours  will 
probably  determine  whether  it  is  possible  to  prevent  or  limit  the  develop- 
ment of  the  exudation.  If  not  successful,  and  the  disease  goes  on  to  its 
fullest  development,  the  same  applications  may  be  continued  every  hour 
or  two  for  the  purpose  of  cleansing  the  throat.  As  already  mentioned, 
a  warm  normal  salt  solution  will  accomplish  the  same  end.  We  now 
employ  it  almost  exclusively.  Park,  consulting  physician  to  the  Willard 
Parker  Hospital,  New  York,  prefers,  in  older  children  and  adults,  irri- 
gation with  a  warm  solution  of  salt  every  hour  or  two,  and  also  every 
three  to  six  hours  to  irrigate  with  some  antiseptic  solution,  especially 
1 :  1000  of  bichloride  of  mercury.  The  irrigation  of  the  throat,  he 
believes,  is  best  carried  out  with  the  fountain  syringe.  In  the  Mu- 
nicipal Hospital  of  Philadelphia  we  were  in  the  habit  of  spraying  the 
throat  every  two  hours  with  peroxide  of  hydrogen.  So  long  as  the 
fauces  are  covered  with  exudate  this  drug  may  be  used  without  dilu- 
tion, but  when  the  exudate  has  thinned  out  very  considerably,  leaving 
the  mucous  membrane  excoriated  and  irritable,  the  peroxide  should 
be  diluted  with  one  or  two  or  more  parts  of  water.  When  the  exudate 
has  almost  entirely  disappeared,  and  the  throat  remains  irritable,  the 
following  application  is  often  useful: 

Jfc — Menthol gr.  x. 

Oil  of  sweet  almonds fS  j.— M. 

Sig. — Apply  in  form  of  spray. 

An  operative  procedure  consisting  of  removing  the  tonsils  at  an  early 
stage  of  diphtheria  has  been  recommended.  Lennox  Browne  and  his 
colleague,  Mr.  Percy  Yakins,  and  also  a  few  other  writers,  claim  to 
have  seen  good  results  follow  the  operation. 


riii<:  TUi<:ATMh:NT  of  Dii'irriihiiaA  697 

The  ol)jec'ti()ns  to  this  treatment  are  that  the  exufhite  is  liable  to 
reform  on  the  cut  surface  and  the  adjacent  parts;  that  the  injury  inflicted 
affords  a  fertile  soil  for  the  propagation  of  the  bacilli,  and  that  the 
exposed  lymphatics  will  [XTmit  of  ready  absorption  f>f  the  tfjxins.  'J'he 
procedure  has  not  met  with  much  favor,  and  w(;  would  strtjiigly  advise 
afjjainst  it. 

Nasal  Diphtheria.  -As  diphtheria  of  the  nose  and  nasopharynx  is 
most  dangerous,  immediate  and  persistent  local  treatmctnt  should  be 
adopted  with  the  object  of  preventing,  as  far  as  possible,  absor})tion  of 
the  noxious  products.  The  treatment  consists  in  frc^fiuent  cleansing 
and  disinfecting  the  nasal  cavities.  The  remedies  usually  employed 
do  not  differ  materially  from  those  recommended  in  faucial  diphtheria. 
The  decomposing  material  and  foul  discharge  should  be  washed  away 
as  fast  as  they  form.  In  order  to  do  this,  it  is  necessary  to  irrigate  the 
nose  very  frequently — often  every  hour,  or  every  two  hours,  day  and 
night.  In  severe  cases  with  a  profuse  fetid  discharge  the  nares  should 
be  kept  clean,  no  matter  how  much  the  child  resists.  The  little  patient 
may  be  restrained  without  suffering  any  harm  by  rolling  him  up  in  a 
sheet.  If  much  exhausted,  the  child  should  not  be  raised  from  the 
recumbent  position  during  the  cleansing  process.  Only  bland  solutions 
should  be  employed,  such  as  boric  acid  (5  to  10  grains  to  the  ounce 
of  w^ater),  chloride  of  sodium  (teaspoonful  to  a  pint  of  w'ater),  or  some 
other  equally  mild  antiseptic  solution.  The  nose  wash  should  always 
be  used  lukewarm,  and  the  more  thorough  the  washing  the  better  it 
is  for  the  patient.  Instillations  wdth  a  small  medicine  dropper,  so  often 
used  by  physicians,  are  not  sufficient.  Nor  will  the  atomizer  convey 
a  sufficient  amount  of  liquid  into  the  nasal  cavities  to  accomplish  the 
purpose  aimed  at.  A  small  (not  too  small)  blunt-pointed  syringe  will 
answer  the  purpose  much  better.  If  carefully  used,  there  is  perhaps 
no  better  irrigator  than  the  fountain  syringe.  It  should  be  held  just 
high  enough  for  the  solution  to  flow  without  undue  pressure,  and  thus 
obviate  any  possibility  of  injury  to  the  middle  ear.  If  the  nose  inclines 
to  bleed,  the  irrigation  should  be  very  slow  and  gentle.  But  if  the  epis- 
taxis  be  free  and  quite  uncontrollable,  as  sometimes  happens,  the 
irrigation  will  have  to  be  dispensed  with.  It  may  then  become  necessary 
to  direct  attention  to  the  hemorrhage.  Alum,  tannic  acid,  Monsel's 
solution,  and  the  like,  may  be  used.  We  have  frequently  found  it 
necessary  to  plug  the  nares.  I/Cnnox  Browne  says  the  hemorrhage  may 
generally  be  arrested  by  syringing  the  nostrils  with  the  following  anti- 
septic solution  at  a  temperature  not  less  than  100°  F. : 

9i — Chlorate  of  potassium >2  oz. 

Bicarbonate  of  sodium 5^  oz. 

Borax J^  oz. 

White  sugar  (in  powder) 1  oz. — M. 

Sig.— A  teaspoonful  dissolved  in  five  or  ten  ounces  of  water  at  100°  F.  and  use  with  nasal  syringe. 

For  the  local  treatment  of  nasal  diphtheria  many  physicians  prefer 
some  of  the  more  active  antiseptic  and  disinfecting  solutions,  such  as 
peroxide    of    hydrogen,    permanganate    of    potassium,    carbolic    acid. 


698  DIPHTHERIA 

bichloride  of  mercury,  and  so  forth.  Peroxide  of  hydrogen  is  quite 
useful  if  it  be  properly  diluted.  It  is  very  irritating  to  the  mucous 
membrane  of  the  nose,  and  will  cause  pain  if  not  diluted  with  8  or  10 
parts  of  water.  Carbolic  acid  has  been  used  in  solution  varying  from 
1:1000  to  10:1000  parts  of  water.  Care  should  be  taken  lest  too 
much  of  this  drug  be  swallowed.  Permanganate  of  potassium  has  been 
highly  recommended.  It  has  been  applied  to  the  fetid  nares  with  a 
cotton  swab,  in  the  strength  of  1 :  250  of  water,  once  or  twice  a  day. 
For  irrigation  it  may  be  used  several  times  a  day  in  a  solution  of  1 :  2000 
to  1:4000. 

For  washing  out  the  nares,  as  well  as  the  fauces,  bichloride  of  mercury 
in  solution  has  many  advocates.  Its  well-known  power  as  a  germ 
destroyer  has  led  to  its  use.  It  would  doubtless  be  more  freely  employed 
were  it  not  for  the  danger  incurred  through  its  poisonous  qualities.  As 
young  children  always  swallow  some  of  the  liquid  that  is  injected  into 
the  nares,  most  physicians  hesitate  to  use  a  solution  which  is  so 
highly  poisonous.  The  same  objection  holds  good  against  its  employ- 
ment for  irrigating  the  fauces.  Among  those  who  recommend  this 
drug  for  washing  out  the  nares  may  be  mentioned  Jacobi.  He  advises 
that  1  part  of  bichloride  of  mercury  })e  mixed  with  10  parts  of  chloride 
of  sodium  or  chloride  of  ammonium,  and  that  from  2000  to  10,000  parts 
of  water  be  added  to  form  a  solution,  which  should  be  used  freely.  He 
says  if  moderate  quantities  of  this  weak  solution  of  mercuric  bichloride  be 
swallowed  while  being  injected  no  harm  is  done.  For  correcting  the 
fetid  odor  from  the  nares,  he  recommends,  besides  some  of  the  solutions 
already  mentioned,  creolin  in  a  1  per  cent,  solution. 

After  some  experience  with  most  of  the  nasal  washes  mentioned  above, 
we  have,  for  the  last  few  years,  settled  down  to  the  use  of  the  warm 
normal  salt  solution  almost  exclusively.  We  find  that  it  answers  the 
purpose  quite  as  well  as  any  of  the  antiseptic  washes,  and  that  it  has 
the  advantage  over  some  others  of  being  perfectly  safe  and  unirritating. 
We  may  add  that  we  have  used  with  benefit  peroxide  of  hydrogen  well 
diluted  with  lime-water. 

Aural  Diphtheria. — But  little  treatment  can  be  applied  to  the  com- 
paratively rare  form  of  acute  median  otitis  of  diphtheritic  character 
other  than  what  is  suitable  for  that  affection  when  it  occurs  ordinarily. 
As  pain  is  not  often  complained  of,  the  condition  is  usually  not  realized 
until  a  purulent  discharge  issues  from  the  external  m^eatus.  Nearly 
all  that  can  be  done  then  is  to  syringe  the  ear  with  a  warm  solution 
of  boric  acid  or  some  other  mild  antiseptic  wash.  At  the  same  time 
the  nose  may  be  irrigated  with  a  similar  solution.  It  is  advisable  that 
Pollitzer  infiation  be  also  employed  with  the  hope  of  clearing  the  Eus- 
tachian tubes. 

The  insufflation  of  dry  powders  into  the  ear  is  not  considered  advis- 
able, as  they  are  likely  to  form  dry  crusts  which  may  prevent  the  escape 
of  the  purulent  material.  Extension  of  the  suppurative  action  to  the 
mastoid  cells  rarely  occurs;  but  when  it  does  occur  surgical  treatment 
applicable  to  that  condition  should  be  resorted  to. 


TTTK  TRI<:ATMKNT  OF  I)! I'llTII KIU A 


699 


Ocular  Diphtheria. — For  diplilliciific  involvcnicnt  nf  the;  conjunctiva, 
fortunately  rare,  the  (^ye  should  he  irri^'ated  frefjuently-  say  every  hour 
— with  a  boric  acid  solution  (ten  grains  to  the  ounce  of  water),  or 
some  other  equally  mild  antiseptic  sohition.  'J'his  will  be  found  difficult 
when  the  eyelids  are  very  much  swollen;  but  an  effort  must  l)e  made 
to  keep  the  pus  from  accuniulatincr  under  the  lids.     Ice  applications, 

Fl«.  98 


Position  of  child  during  irrigation  of  tliroat  and  nose.    (After  Park.l 

in  the  form  of  iced  cloths,  are  always  indicated  at  first;  but  later  it  may 
be  better  to  use  %varm  applications.  A  strong  solution  of  nitrate  of 
silver  may  be  applied  to  the  pseudomembrane  on  the  palpebral  con- 
junctiva if  care  be  taken  to  neutrahze  the  silver  salt  immediately  with 
a  solution  of  chloride  of  sodium^ 

According  to  Lennox  Browne,^^Hermann,  of  Breslau,  has  employed 
very  efficaciously  hourly  pencillings  of  the  affected  eyelids  with  a  5  per 


700  DIPHTHERIA 

cent,  solution  of  benzoate  of  sodium,  and  declares  that  since  he  began 
to  use  this  treatment  no  patient  under  his  care  with  this  form  of  diph- 
theria has  lost  an  eye. 

Paralysis  of  the  muscles  of  the  eye  occurring  as  a  sequel  to  diphtheria 
calls  for  no  special  treatment.  It  will  almost  always  disappear  entirely 
in  the  course  of  two  or  three  months. 

Constitutional  Treatment. — As  diphtheria  begins  as  a  local  disease 
very  little  internal  treatment  is  required  at  the  onset.  Constitutional 
disturbance,  however,  occurs  early,  partly  as  a  result  of  the  local  disease, 
but  more  especially  from  absorption  of  the  toxic  products  of  the  diph- 
theria bacilli  and  the  associated  organisms.  The  prostrating  effects  of 
this  poison  are  well  known.  The  indications  for  internal  remedies  may 
be  stated  as  follows :  To  aid  the  system  in  the  elimination  of  the  poison ; 
to  reinforce  the  debilitated  vasomotor  system;  to  improve  the  quality 
of  the  blood;  to  combat  the  poisonous  effects  of  the  toxins;  to  sustain 
the  vital  powers;  and,  lastly,  to  conduct  to  a  favorable  termination  the 
secondary  affections  that  may  arise. 

At  the  outset  of  the  disease  it  is  well  to  administer  a  gentle  purge. 
For  this  purpose  there  is  perhaps  nothing  preferable  to  calomel.  Liquor 
ammonii  acetatis  (U.  S.  P.)  is  useful,  as  it  tends  to  increase  the  secretions 
of  the  skin  and  kidneys.  Water  may  be  allowed  ad  libitum.  Small 
pieces  of  ice  held  in  the  mouth  will  often  have  a  soothing  effect  on  the 
inflamed  and  painful  fauces.  Should  the  temperature  of  the  patient 
be  high,  no  attempt  should  be  made  to  reduce  it  by  the  internal  admin- 
istration of  antipyretic  drugs,  especially  the  coal-tar  products,  as  they 
ai'e  too  depressing.  It  is  better  to  trust  to  tepid  bathing.  Bathing  has 
the  additional  advantage  of  keeping  the  function  of  the  skin  active. 
At  this  early  stage  there  is  no  article  of  diet  equal  to  milk.  There  is, 
however,  no  objection  to  beef-tea  and  broth. 

As  soon  as  the  diphtherial  character  of  the  disease  is  recognized  iron 
should  be  administered.  For  the  past  fifty  years  this  drug  has  had  the 
confidence  of  physicians  in  this  country,  as  well  as  those  in  most  of  the 
European  countries,  and  by  many  it  is  regarded  as  our  sheet-anchor 
in  the  constitutional  treatment  of  diphtheria. 

The  preparation  of  iron  that  has  achieved  the  greatest  reputation  in 
this  disease  is  the  tinctura  ferri  chloridi.  It  is  believed  to  have  both  a 
local  and  general  effect.  It  should  be  administered  frequently  and  in 
positive  doses.  A  child  of  one  year  may  take  as  much  as  a  fluidrachm 
in  twenty-four  hours,  and  a  child  of  three  to  five  years  from  two  to 
three  fluidrachms  in  the  same  period  of  time.  It  should  be  admin- 
istered every  hour  or  two.  Some  WTiters  advise  that  it  be  given  every 
fifteen,  twenty,  or  thirty  minutes.  It  should  always  be  given  diluted 
with  a  little  water,  so  that  the  dose  is  about  a  teaspoonful.  The  addition 
of  glycerin  makes  the  drug  more  palatable.  One  part  of  glycerin  to 
three  parts  of  water  makes  a  very  good  vehicle.  If  there  is  too  much 
dilution  no  local  effect  can  be  expected  from  the  drug.  As  a  rule,  it  is 
well  borne  by  the  stomach;  but  there  are  exceptional  cases  in  which 
it  is  not  tolerated  at  all. 


77//';  Tfi/'JATM/'JN'/'  Oh'  1)1 1'llTII HlilA  701 

Jacohi,  aftor  iisin^  tlii.s  pre[)aratif)ii  of  iron  for  many  years,  cxprrssps 
great  confidence  in  it.  He  feels  sure  he  has  seen  many  bacJ  cases  recover 
through  its  use.  But  he  has  met  with  some  cases  in  which  its  action 
was  not  so  satisfactory.  lie  says:  "Still,  I  have  often  been  so  .situatr-f] 
that  1  had  to  give  it  up  in  pecidiar  cases.  'I'hey  were  those  in  which 
the  main  symj)toms  were  of  so  intense  a  sepsis  that  tlu;  iron  and  other 
rational  methods  of  treatment  were  not  powerful  enough  to  prevent 
the  rapid  progress  of  the  disease.  Children  with  nasopharyngeal  diph- 
theria, large  glandular  swelling,  feeble  heart,  and  fref]uent  pulse, 
thorough  sepsis,  and  irritable  stomach  })esides,  those  in  whom  large 
doses  of  stimulants,  general  and  cardiac,  may  pcjssibly  bring  any  relief, 
are  better  oft"  without  the  iron.  When  the  circumstances  are  such  as  to 
leave  the  choice  between  iron  and  alcohol,  it  is  best  to  omit  the  iron 
and  rely  on  alcoholic  stimulants  mostly.  The  quantities  required  are 
so  large  that  the  absorbent  powers  of  the  digestive  tract  are  no  longer 
sufficient  for  both." 

J.  Lewis  Smith  regards  the  ferruginous  preparations  as  holding  an 
important  place  in  the  treatment  of  diphtheria,  and  says  the  one  which 
has  stood  the  test  of  experience  is  the  tincture  of  the  chloride  of  iron. 
He  believes  it  should  be  given  in  large  and  frequent  doses,  as  five  drops 
hourly  to  a  child  of  three  years.  He  thinks  it  probable  that  those  Avho 
have  not  observed  its  good  effects  have  treated  unusually  bad  cases 
or  have  given  the  medicine  in  small  and  inadequate  doses.  The  best 
vehicle,  he  says,  is  glycerin  and  water. 

Some  writers  maintain  that  an  effort  should  be  made  to  saturate  the 
system  as  soon  as  possible  with  this  drug,  and,  with  this  object  in  \iew, 
recommend  that  it  be  given  in  as  large  and  frequently  repeated  doses 
as  the  stomach  will  tolerate.  Ferguson,  according  to  the  author  last 
mentioned,  believes  that  this  preparation  of  iron  when  freely  admin- 
istered partially  arrests  the  blood  change  in  diphtheria,  and  he  recom- 
mends for  a  child  of  ten  years  the  following  mixture : 

1^ — Tinct.  ferri  chloridi S  j.  • 

Syr.  simplicis .    3  iij  — M. 

Sig.— One  teaspoonful  hourly  in  waler. 

If  the  stomach  cannot  tolerate  this  dose,  it  is  advised  that  half  a 
teaspoonful  be  given  every  half-hour. 

Prof.  Joseph  E.  Winters,^  of  New  York,  says  that  he  has  administered 
to  a  child  of  eight  years  as  large  and  frequent  doses  of  the  tincture  of 
the  chloride  of  iron  as  two  drachms,  in  combination  with  glycerin,  every 
half-hour  for  forty-eight  hours  with  marked  benefit.  And  J.  Lewis 
Smith  cites  an  instance  in  which  a  woman,  aged  twenty-two  years, 
greatly  prostrated,  having  an  excessive  amount  of  exudate  in  the 
throat,  and  a  very  fetid  breath,  took  daily  one  and  a  half  fiuidounces 
of  the  iron  for  ten  days.  But,  he  remarks,  "it  is  only  in  tlie  most  severe 
or  malignant  form  of  the  disease,  the  form  described  by  Sanne  as  septic 
phlegmonous,  that  such  large  doses  are  proper  or  are  required."     He 

1  Diphtheria  and  its  Management,  1SS5. 


702  DIPHTHERIA 

believes,  as  do  most  physicians  of  the  present  day,  that  in  the  average 
case  of  diphtheria  five  drops  given  hourly  is  the  proper  dose  for  a 
child  of  three  years. 

We  have  used  in  our  hospital  work  for  many  years  the  ferric  chloride 
in  doses  practically  the  same  as  those  last  mentioned;  but  we  prefer 
to  combine  it  with  the  bichloride  of  mercury,  as  in  the  following  formula : 

^ — Hydrargyri  chloridi  corrosivi g^-  % 

Tinct.  ferri  chloridi 5j. 

Syrup,  simplicis S  j. 

Aquae q.  s.  ad    fS  iij.— M. 

Sig. — For  a  child  of  three  years,  one  fluidrachm  iu  a  little  water  every  two  hours. 

The  internal  use  of  bichloride  of  mercury  in  the  treatment  of  diph- 
theria is  not  new.  It  was  employed  in  this  country  as  far  back  as  1860, 
by  Dr.  Tappan,  of  Ohio,  with  asserted  benefit.  It  has,  however,  been 
used  more  frequently  of  late  years,  since  it  has  been  shown  to  be  one  of 
the  most  active  germicides  in  medicine.  The  accepted  theory  of  the 
microbic  origin  of  diphtheria  has  led  to  the  employment  of  this  drug 
by  many  practitioners  in  the  belief  that  when  given  internally  it  pene- 
trates all  parts  of  the  system,  destroying  all  micro-organisms  with  which 
it  comes  in  contact.  But  as  diphtheria  begins  as  a  local  disease  and 
becomes  a  systemic  affection  later,  not  because  the  specific  micro- 
organisms enter  the  circulation — for  in  only  rare  instances  have  they 
been  found  in  the  blood — but  because  of  the  absorption  of  their  poisonous 
products,  it,  therefore,  may  be  that  the  remedial  power  of  corrosive 
sublimate  is  limited  to  its  local  eft'ect  upon  the  organisms  in  the  throat 
and  pharynx.  Whichever  way  its  influence  is  exerted,  locally  or  consti- 
tutionally, it  has  been  found  by  many  physicians  to  be  very  useful  in 
diminishing  the  virulence  of  diphtheria  and  increasing  the  chances  of 
recovery. 

Though  this  drug  has  been  widely  employed  in  diphtheria,  and  at 
times  administered  in  what  would  appear  to  be  dangerous  doses,  very 
few  reports  can  be  found  of  its  toxic  or  injurious  effect.  Dr.  Grant^ 
administered  to  a  child  of  four  years  one-half  grain  of  corrosive  sublimate 
every  half-hour  until  six  doses  were  taken,  and  then  hourly  during  the 
remainder  of  the  day,  every  two  hours  on  the  second  day,  and  on  subse- 
quent days  at  longer  intervals.  Jacobi  has  also  administered  it  freely, 
but  not  in  such  heroic  doses  as  just  mentioned.  He  states  that  an 
infant  a  year  old  may  take  half  a  grain  every  twenty-four  hours — of 
course,  in  divided  doses — for  many  days  in  succession,  with  very  little, 
if  any,  intestinal  disorder,  and  with  no  stomatitis. 

While  large  doses  may  be  justifiable  in  extremely  severe  cases,  we 
believe  that  smaller  and  safer  doses  are  sufficient  for  general  use.  W^e 
agree  with  J.  Lewis  Smith,  who  says:  "In  ordinary  cases  the  following 
may  perhaps  be  regarded  as  about  the  proper  quantities  which  should 
be  administered  in  divided  doses  in  twenty-four  hours:  For  a  child  of 
two  years,  gr.  |  (gr.  ^t  every  two  hours) ;  for  a  child  of  four  years,  gr.  | 

1  Quoted  by  J.  Lewis  Smith,  Cyclopedia  of  the  Diseases  of  Children,  by  Keating. 


77//';  Till<:ATMI<:NT  OF  DII'IITIIF.UIA  703 

(gr,  -^^  every  two  lionrsj;  for  a  cliild  of  six  years,  ^r.  \  (\iv.  .j',;  every  two 
hours);  and  for  a  child  of  ten  years,  ^r.  h  (^'r.  ./,  every  two  hoursj." 

Calomel. — Calomel  as  a  remedy  in  diphtlieria  has  its  advo(;ates.  It 
has  been  recommended  with  the  purpose  of  securing  both  its  cathartic 
and  alterative  elfects.  It  may  be  useful  as  a  gentle  cathartic  at  the 
beginning  of  an  attack,  but  to  continue  catharsis  after  the  flisease  is 
fully  developed  seems  ol)jectionable  on  account  of  its  tendency  to 
weaken  the  patient  and  increase  the  ana?mia  which  so  soon  becomes 
manifest  in  all  severe  cases,  whatever  the  treatment.  Much  more  is 
claimed  for  it  when  administered  in  a  fractional  part  of  a  grain  at 
frequent  intervals.  Many  physicians  of  ample  experience  recommend 
it  very  highly  in  doses  of  one-tenth  to  one-quarter  of  a  grain,  repeated 
every  hour  or  two.  Some  advise  that  a  fractional  part  of  a  grain  in 
powder  form  be  placed  on  the  tongue  every  hour  or  two,  or  even  more 
frequently,  and  allowed  to  disappear  gradually.  It  is  claimed  that 
when  given  in  this  way  it  acts  both  locally  and  constitutionally.  Its 
tendency  to  act  on  the  bowels  may  be  obviated  by  the  administration 
of  a  little  paregoric  at  proper  intervals. 

Potassium  Chlorate. — Potassium  chlorate  has  been  used  in  the  treat- 
ment of  diphtheria  for  almost  as  long  a  time  as  the  tincture  of  the 
chloride  of  iron.  It  was  formerly  more  often  employed  than  at  present, 
but  it  still  has  many  admirers.  Its  great  efficacy  in  stomatitis  has 
encouraged  the  belief  that  it  is  also  useful  in  diphtheritic  pharyngitis. 
But,  as  the  results  have  been  disappointing,  and  the  action  of  the  drug 
tends  to  weaken  the  patient  and  injure  the  kidneys,  especially  when 
administered  in  doses  believed  to  be  sufficiently  large  to  be  of  service, 
it  has,  to  a  great  degree,  fallen  into  disuse.  Jules  Simon  says  that 
while  it  acts  wonderfully  well  in  stomatitis  he  has  obtained  no  benefit 
from  it  in  diphtheria.  Its  tendency  to  cause  albuminuria  and  nephritis 
when  taken  in  large  doses  is  well  known.  Where  death  has  resulted 
from  an  overdose  of  this  drug  the  kidneys  have  been  found  greatly 
damaged. 

Potassium  chlorate  in  combination  with  the  tincture  of  the  chloride 
of  iron  was,  a  few  years  ago,  almost  universally  regarded  as  the  remedy 
far  excellence  in  diphtheria.  The  following  formula,  vnXh.  some  variations 
in  the  proportion  of  the  ingredients,  w^as  for  a  long  time  a  favorite 
prescription  with  most  physicians  of  this  country,  and  is  still  used 
by  many: 

P:— Potassii  chlorat 5  j. 

Tinct.  ferri  ehloridi f5  ij. 

Acidi  muriat.  dilut gtt.  x. 

Syr.  simplicis fS  j- 

Aquse q.  s.  ad  fs  iv.— M 

Sig.— One  teaspoonful  every  hour  or  two  hours  iu  a  little  water. 

A  child  of  five  years  may  take  one-half  of  the  above  mixture  in  the 
course  of  twenty-four  hours. 

Dr.  Thomas  ]\I.  Drysdale,  of  Philadelphia,  who  has  had  considerable 
experience  in  the  treatment  of  diphtheria,  claims  that  chlorate  of  potash 


704  DIPHTHERIA 

is  so  efficacious  as  to  be  almost  a  specific  in  this  disease.  He  employs 
it  in  large  doses.  To  an  adult  he  gives  fifteen  grains,  and  to  a  child  of 
tv/elve  years  seven  and  a  half  grains,  every  two  hours.  In  such  doses 
he  does  not  fear  any  deleterious  effect  on  the  kidneys.  In  laryngeal 
diphtheria  he  recommends  the  following  formula : 

Jfc — Potassii  chlorat 5  ij. 

Syr.  limonis .       .    fX  j. 

Aquae fS  iij.— M. 

Sig.— For  a  child  under  two  years  one  teaspoonful,  and  for  a  child  from  two  to  ten  years  two 
tuaspoonfuls,  every  half-hour  in  urgent  cases. 

After  an  extensive  use  of  potassium  chlorate  in  diphtheria,  and  failing 
to  obtain  the  favorable  results  claimed  for  it,  we  have  abandoned  it 
entirely.  We  feel  inclined  to  agree  with  that  noted  clinician  of  his  day, 
J.  Lewis  Smith,  who  says:  "From  what  is  known  of  its  action,  it  would 
probably  be  better  to  abandon  its  use  in  diphtheria,  since  it  is  a  remedy 
of  doubtful  efficacy  for  throat  affections.  If  it  be  employed,  it  should 
certainly  be  administered  in  small  doses  sufficiently  diluted.  If  it  be 
prescribed,  it  should  not,  I  think,  be  in  larger  quantity  than  half  a 
drachm  in  twenty-four  hours  for  a  child  of  five  years." 

Turpentine. — Turpentine  has  its  advocates  in  the  treatment  of  this 
disease.  It  has  been  employed  both  locally  and  internally,  with  the 
result,  as  some  writers  believe,  of  arresting  the  formation  and  spread 
of  the  exudation,  and  preventing  the  secondary  toxic  effects.  Cases 
have  been  reported  in  which  severe  croupy  symptoms  quickly  dis- 
appeared under  teaspoonful  doses  of  pure  turpentine,  and  the  patient, 
in  one  instance,  recovered  without  tracheotomy,  which  was  before 
thought  necessary.  The  dose  more  commonly  employed  has  varied 
from  ten  minims  to  a  teaspoonful,  one  to  three  times  daily,  in  milk, 
sweetened  water,  or  gruel. 

Good  results  have  been  reported  from  the  use  of  this  agent  by  men 
of  large  experience  and  good  judgment,  among  whom  may  be  mentioned 
Baruch  and  Jacobi.  Dr.  Llewellyn,  of  Washington,  D.  C,  speaks  favor- 
ably of  the  action  of  turpentine  when  vaporized  and  inhaled.  Its  sup- 
posed efficacy  is  attributed  to  the  fact  that  it  is  antiseptic  and  germi- 
cidal in  its  action.  J.  Lewis  Smith  says  he  has  employed  the  vapor  of 
turpentine  with  apparently  good  results.  The  mixture  he  recommends 
for  vaporization  is  as  follows : 

P;— Acidi  carbolici, 

Ol.  eucalypti ad    S  j. 

Spts.  terebinth S  viij. — M. 

Two  tablespoonfuls  of  this  mixture  are  added  to  one  quart  of  water, 
which  is  placed  in  a  shallow  vessel  with  a  broad  surface,  and  maintained 
in  a  constant  ebullition  or  simmering  upon  a  gas  or  other  stove.  He 
thinks  that  the  vapor  thus  generated,  "in  passing  over  the  inflamed 
surfaces,  which  are  the  seat  of  the  exudate,  with  every  inspiration, 
probably  produces  more  or  less  local  disinfection,  apart  from  the 
systemic  disinfection  which  it  may  cause   by  entering  the  blood  and 


77//';  TUJ'JATMl'JNT  Ol''  l>l I'llTII KKI A  705 

the  tissues  generally."  We  feel  that,  such  ;i  result  is  scarcely  to  be 
expected  from  turj)entine.  As  to  its  alleged  cHicacy  in  dij)hth(Tia,  how- 
ever, we  are  unable  to  speak  from  any  personal  experience. 

Sodium  Benzoate.  Sodium  benzoate,  for  internal  as  well  as  local  use, 
has  been  highly  reconunciuJed  by  a  nnnd)cr  of  writ,(*rs.  Dr.  I.  N.  Ix>ve 
regarded  it  as  efficacious  in  from  five  to  fifteen  grain  doses.  Some; 
observers  claim  to  have  shown  that  it  arrests  the  growth  of  micro- 
organisms. According  to  J.  Lewis  Smith,  II(;lferich,  Graham  Brown, 
and  Sanne  beli(>ve  that  it  is  a  specific  against  the  virtis  of  diphtheria. 
Smith  says:  "On  the  other  hand,  M.  Dumas,  surgeon  to  the  Hopital 
de  Cette,  has  not  derived  any  marked  benefit  from  its  use,  and  Prof. 
A.  Jacobi  says  that  it  does  not  deserve  the  eulogies  bestowed  upon  it 
from  theoretical  reasonings." 

Such  drugs  as  pilocarpine,  copaiba,  cubebs,  resorcin,  hyposulphite  of 
sodium,  and  many  others,  have  been  recommended  from  tim(!  to  time, 
but  none  of  them  deserves  any  prominent  place  among  the  therapeutic 
agents  useful  in  the  treatment  of  diphtheria.  Of  the  internal  remedies 
to  which  prominence  has  been  given  we  would  consider  most  useful 
the  tincture  of  the  chloride  of  iron  and  bichloride  of  mercury.  To 
these  we  would  add  strychnine,  digitalis,  and  alcohol.  But  as  diphtheria 
is  a  disease  of  variable  type,  we  must  treat  each  case  according  to  the 
indications. 

Strychnine.— Strychnine  is  useful  to  combat  cardiac  depression.  It 
may  be  given  combined  with  tincture  of  the  chloride  of  iron,  or  it  may 
be  administered  separately.  It  is  often  advisable  to  inject  it  hypo- 
dermically.  The  dose  should  be  adapted  to  the  age  of  the  child,  but 
the  amount  which  children  of  tender  years  will  bear  without  harm  is 
astonishing,  especially  when  in  a  condition  of  toxaemia.  A  child  of 
three  years  will  take  y^-g-  of  a  grain  every  four  to  eight  hours;  in  an 
emergency  a  larger  dose  will  be  borne. 

Digitalis. — Digitalis  is  also  of  advantage  when  the  heart  action  is 
weak.  In  case  of  irritability  of  the  stomach,  which  always  occurs  in 
profound  toxiemia,  digitalin  may  be  administered  hypodermically. 
Strophanthus,  sparteine,  caffeine,  and  the  like,  are  also  recommended 
to  combat  cardiac  failure.  To  a  child  of  five  years  two  drops  and  some- 
times as  much  as  four  drops  of  the  tincture  of  digitalis  may  be  given 
every  four  hours,  or  from  one  to  six  drops  of  the  tincture  of  strophanthus. 
In  a  great  emergency  one  or  two  unusually  large  doses  of  these  drugs 
may  be  administered,  followed  by  the  more  ordinary  dose  at  proper 
intervals. 

Citrate  of  caffeine  may  be  used  in  doses  from  \  grain  to  5  grains. 
Jacobi  says:  "For  subcutaneous  injections  the  salicylate  (or  benzoate) 
of  caffeine  and  sodium,  which  readily  dissolves  in  2  parts  of  water, 
is  valuable  for  emergencies,  in  occasional  doses  of  from  gr.  1  to  5 
(6  to  30  cgm.),  in  from  2  to  10  minims  of  water." 

Alcohol. — There  are  but  few  other  diseases  which  demand  more 
imperatively  the  use  of  alcohol  than  does  diphtheria.  Mild  cases  will 
frequently  do  well  without  stimulants;  but  no  case,  however  mild  it  may 

45 


706  DIPHTHERIA 

seem  to  be,  should  be  considered  out  of  danger  until  recovery  has  taken 
place.  In  view  of  the  well-known  depressing  effects  of  the  poison  of 
this  disease,  even  mild  cases  should  receive  small  doses  of  some  stimulant. 
Severe  cases  require  a  very  liberal  amount  of  alcohol  in  some  form; 
it  should  be  commenced  early  in  the  disease  by  giving  small  doses  at 
first,  and  increasing  the  amount  as  the  indications  for  its  use  become 
more  pronounced.  Whenever  the  heart  action  shows  any  loss  of  force, 
or  the  first  sound  of  the  heart  becomes  less  distinct,  or  pallor  is  noticed, 
or  the  patient's  strength  is  declining,  large  and  frequent  doses  of  some 
active  stimulant  are  required.  It  matters  little  how  the  stimulant  is 
administered,  whether  plain  or  in  the  form  of  milk  punch  or  wine 
whey,  provided  that  sufficient  is  given  to  produce  the  desired  effect. 

Whiskey  is  more  often  employed,  for  the  reason,  doubtless,  that  good 
whiskey  can  be  more  easily  obtained  than  good  brandy.  If  whiskey 
disagrees  with  a  patient  brandy  should  be  tried.  Either  of  these 
stimulants  may  be  administered  in  teaspoonful  doses  properly  diluted, 
to  a  child  of  five  years.  In  septic  cases  the  amount  of  alcohol  which 
a  child  may  take  without  showing  evidence  of  intoxication  is  nothing 
less  than  astonishing.  In  this  type  of  diphtheria  it  is  not  unusual  for 
a  child  of  five  years  to  take  one  teaspoonful  or  even  two  teaspoonfuls 
of  whiskey  every  hour,  making  the  daily  amount  ingested  from  three 
to  six  ounces.  While  alcohol  is  ordinarily  contraindicated  in  albuminuria 
or  nephritis,  yet  rather  than  lose  the  support  of  so  important  an  ally 
in  combating  toxsemia,  it  should,  nevertheless,  be  cautiously  em- 
ployed. 

If  the  toxaemia  be  well  marked,  alcohol  in  doses  however  large  will  not 
save  the  life  of  the  patient,  but  it  may  prolong  it  somewhat.  When 
the  heart's  action  begins  to  wane,  it  is  difficult  to  restore  it.  W^e  cannot 
recollect  of  ever  having  seen  a  patient  recover  when  the  pulse  was 
once  lost  at  the  wrist.  Hence,  the  great  importance  of  beginning  the 
use  of  alcohol  early.  If  the  stomach  will  not  tolerate  either  whiskey 
or  brandy  a  good  wine  should  be  substituted.  We  have  found  cham- 
pagne useful  when  the  stomach  is  irritable.  Aromatic  spirit  <  f  ammonia 
is  a  good  stimulant,  and  may  be  used  temporarily,  if  it  be  found  more 
agreeable  to  the  stmoch. 

Attention  should  be  given  to  the  diet  of  a  diphtheria  patient  throughout 
the  entire  illness.  In  the  acute  stage  of  the  disease  all  food  should  be 
of  a  fluid  character,  consisting  of  milk,  beef-tea,  broths,  and  the  like. 
It  may  be  necessary  to  peptonize  these,  though,  as  a  rule,  the  digestion 
is  not  bad.  Ice  and  iced  drinks  may  be  allowed.  Should  there  be  a 
craving  after  cold  articles,  cold  junket,  frozen  custards,  and  frozen 
beef-tea  may  be  given.  Soft-boiled  eggs  are  useful  when  the  patient 
is  able  to  take  them.  Later,  corn-starch,  rice  pudding,  bread  and 
butter,  fruit  and  vegetables  may  be  added.  As  early  as  possible  a  full, 
liberal  diet  should  be  allowed. 

In  regard  to  the  complications  of  diphtheria,  we  feel  that  but  little 
time  need  be  spent  here  in  discussing  their  treatment.  Adenitis,  otitis 
media,  bronchopneumonia,  and  nephritis  are  the  more  common  com- 


77//';  TREATMENT  ()/<'  1)1 1'llTII IIIU A  707 

plications  ericoiintcnHl,  and  they  j)rcs(;nt  no  incjicatioiis  for  treatment 
at  all  (liiTerent  tlian  wlicui  these;  all'ections  oeeiir  from  other  causes. 

The  paralysis  of  diphtlieria,  however,  dillers  from  the;  other  compli- 
cations, in  that  it  is  [jcculiar  to  the  disease.  It  cannot  be  prevented; 
and  drugs  avail  but  little  in  hastening  the  cure,  ""d'he  most  dang<;rous 
form  is  cardiax;  j)aralysis.  It  is  well  to  anticipate  this  cf>nflition  by 
keeping  the  patient  (juiet,  and  endeavoring  to  sustain  th(;  strength  of 
the  heart  by  administering  digitalis,  strychnine,  alcohol,  and  other 
cardiac  tonics.  As  we  have  already  seen,  cardiac  paralysis  often  develops 
suddenly,  and  the  patient  may  die  before  the  })hysician  can  be  summoned. 
The  earliest  symptoms  of  this  affection  should  receive  prompt  attention. 
The  patient  should  remain  as  (juiet  as  possible  in  lied,  with  his  head 
low.  It  is  sometimes  advisable  to  raise  the  foot  of  the  bed  slightly. 
He  should  remain  in  the  recumbent  position  when  taking  food,  water, 
or  medicine.  Under  no  circumstances  should  he  be  allowed  to  leave 
the  bed  to  empty  his  bladder  or  rectum.  Whiskey  or  brandy  should 
be  given  in  doses  sufficiently  large  to  be  of  service.  If  the  stomach  be 
at  all  irritable,  champagne  is  to  be  preferred.  In  case  of  a  sudden 
seizure  of  heart-failure,  hypodermic  injections  of  brandy  should  be 
administered.  The  hypodermic  use  of  strychnine  will  also  aid  in 
sustaining  the  heart  action.  Ammonia,  camphor,  musk,  and  the  like 
sometimes  serve  as  useful  auxiliaries.  At  the  same  time  the  general 
strength  of  the  patient  should  be  well  sustained  with  a  liberal  amount 
of  nourishing  and  easily  digestible  food,  such  as  peptonized  milk, 
beef-tea,  broths,  or  some  of  the  concentrated  foods  designed  for  invalids 
with  feeble  digestion.  For  large  children  and  adults  soft-boiled  eggs 
are  useful,  unless  the  digestion  be  very  feeble.  When  improvement 
takes  place  the  physician  should  see  that  the  patient  does  not  get  out 
of  bed  too  soon. 

For  the  multiple  paralysis  which  follows  diphtheria  the  patient 
requires  sustaining  remedies,  such  as  iron,  quinine,  strychnine,  and 
alcoholic  stimulants.  Particular  attention  should  be  given  to  the  diet, 
as  there  is  ordinarily  marked  debility  and  anaemia,  with  a  feeble  digestion. 
Beyond  the  employment  of  a  sustaining  treatment  we  do  not  believe 
that  much  can  be  done  to  hasten  the  cure  of  diphtheritic  paralysis. 
Some  physicians  believe  that  they  have  derived  benefit  from  electricity, 
but  a  large  number  speak  doubtfully  of  its  efficacy. 

As  strychnine  is  known  to  be  efficacious  in  many  other  forms  of 
paralysis,  it  is  frequently  employed  on  general  principles  for  the  neuroses 
of  diphtheria.  Some  observers  have  reported  good  results  from  its 
use,  while  others  question  its  utility,  except  as  a  tonic.  Prof.  Henoch, 
Reinard,  and  Gerasimow  claim  to  have  hastened  the  cure  of  diphtheritic 
paralysis  by  hypodermic  injections  of  strychnine.  This  drug  is  said 
to  have  been  employed  in  one  case  (a  boy,  aged  three  and  one-half  years) 
with  marked  improvement  in  the  tonicity  of  the  muscles  within  twenty- 
four  hours  after  the  first  dose,  wdiich  consisted  of  about  -^  oi  &  grain, 
and  this  was  repeated  each  day  for  fifteen  days,  when  the  patient  was 
considered  cured.    In.  another  case  (a  child,  aged  six  years)  a  complete 


708  DIPHTHERIA 

cure  is  reported  from  hypodermics  of  about  -^-^  of  a  grain  daily  for 
seven  days,  followed  by  ^V  of  a  grain  each  day  for  twelve  days  longer. 

We  are  not  convinced  that  strychnine  possesses  any  special  value 
as  a  remedy  in  diphtheritic  paralysis.  It  is  our  opinion  that  tonics 
and  a  sustaining  diet  will  do  more  toward  helping  a  patient  through 
an  attack  than  anything  else.  The  paralysis  is  seldom  permanent. 
We  have  never  known  it  to  be  so.  In  most  cases  complete  recovery 
takes  place  in  from  two  to  four  months. 

There  is,  however,  one  thing  connected  with  the  treatment  of  multiple 
paralysis  of  diphtheria  which  is  of  great  importance.  We  refer  to  the 
care  a  patient  should  receive  when  unable  to  swallow.  In  all  severe 
cases  deglutition  is  difficult  and  sometimes  impossible.  It  is  necessary 
then  to  sustain  the  strength  of  the  patient  by  nutritive  enemata,  or  by 
introducing  food  into  the  stomach  by  means  of  an  oesophageal  tube. 
The  latter  is  preferable,  as  it  gives  us  a  better  idea  of  the  amount  of 
nourishment  that  is  utilized.  The  patient  should  be  fed  every  four 
hours,  and  with  each  feeding  there  should  be  administered  also  such 
medicine,  stimulants,  and  the  like,  as  may  be  required.  It  is  not  often 
that  a  patient  has  to  be  fed  with  the  oesophageal  tube  for  a  longer  time 
than  two  weeks.  We  recall  one  case  of  paralysis  in  which  this  means 
of  feeding  was  employed  for  sixteen  days.  By  holding  the  jaws  slightly 
apart  with  the  gag  of  the  intubation  set,  it  is  not  difficult  to  introduce 
the  tube  through  the  mouth  into  the  stomach.  The  tube  will  slip 
down  more  easily  if  slightly  oiled.  If  a  patient  be  safely  carried  over 
the  period  of  difficult  or  impossible  deglutition,  his  chances  of  complete 
recovery  may  be  considered  very  good. 

Treatment  of  Laryngeal  Diphtheria  (Membranous  Croup). 

It  is  deemed  most  convenient  to  consider  the  treatment  of  laryngeal 
diphtheria  under  three  heads: 

1.  Prevention. 

2.  The  means  of  promoting  the  separation  and  expulsion  of  the 
pseudomembrane. 

3.  The  adoption  of  such  operative  measures  as  will  overcome  the 
mechanical  obstruction  to  respiration. 

Prevention. — ^There  is  no  certain  way  of  preventing  laryngeal  diph- 
theria, unless  it  be  to  guard  the  child  against  exposure  to  the  infection 
of  the  disease.  But  when  diphtheria  begins  in  the  fauces  something 
may  be  done  in  the  way  of  diminishing  the  liability  of  the  membrane 
extending  into  the  larynx.  We  have  seen  that  a  mucous  membrane 
which  is  inflamed  or  congested  is  thereby  predisposed  to  the  diphtheritic 
process.  It  is  advisable,  therefore,  to  guard  the  patient,  as  far  as 
possible,  against  the  development  of  a  catarrhal  affection  of  the  larynx. 
As  soon  as  faucial  diphtheria  is  recognized,  the  physician  should  see 
that  the  child  is  placed  in  a  room  of  equable  temperature  and  free  from 
draughts.  If  the  case  occur  in  the  winter  season,  and  the  atmosphere 
of  the  room  is  warmed  by  dry  heat,  it  would  be  well  to  moisten  the  air 


TIIK  rilF.ATMKNT  Ol''  1)1 1'lll'll HIU A  70f) 

by  the  addition  of  a  little  steam.  It  has  been  suggested  that  the  steaui 
be  impregnated  with  eiicaly|)tol  or  some  other  fragrant  essential  oil, 
but  we  do  not  tliink  tliat  this  is  of  any  great  importanee.  (^are  should 
be  taken  not  to  overcharge  tiie  air  of  the  room  with  irioisture,,  as  this 
would  be  more  harmful  than  benefieial.  in  the  sununer  months  fresh 
air  should  be  freely  admitted,  with  precautions  against  draughts,  and 
steam  may,  be  dispensed  with. 

Drugs  are  of  no  avail  in  preventing  laryngeal  involvement.  Anti- 
toxin may  be  of  great  service  as  a  preventive  measure,  but  we  have 
seen  the  pseudomembrane  in  the  fauces  extend  into  the  larynx  on  a 
number  of  occasions  even  after  the  administration  of  antitoxin. 

Means  of  Promoting  Separation  and  Expulsion  of  the  Pseudo- 
membrane. — When  false  membrane  has  formed  in  the  larynx,  constitut- 
ing membranous  croup,  nature's  method  of  effecting  a  cure  consists 
in  the  gradual  disintegration  of  the  membrane,  or  its  separation  and 
expulsion.  How  this  process  may  be  best  promoted  has  always  been  a 
problem  difficult  of  solution.  Emetics  have  been  freely  employed, 
and  of  these  turpeth  mineral  was  for  a  long  time  believed  to  be  espe- 
cially useful.  But  they  can  be  of  no  service  unless  the  membrane  be 
in  good  part  detached.  The  persistent  use  of  emetics  is  objectionable 
on  account  of  their  depressing  effect.  When,  however,  a  flapping 
sound  is  heard  in  the  larynx,  indicating  the  presence  of  partly  detached 
membrane,  an  emetic  should  not  be  withheld  except  in  cases  of  profound 
asthenia.  The  one  selected  should  be  of  that  class  which  excites 
prompt  and  efficient  vomiting  without  producing  prolonged  nausea 
and  depression.  Among  those  to  be  preferred  we  would  mention  ipe- 
cacuanha, powdered  alum,  and  sulphate  of  zinc. 

Warm  Steam. — For  the  purpose  of  hastening  the  separation  of  the 
false  membrane  in  croup  there  is  a  general  consensus  of  opinion  in 
favor  of  the  continuous  inhalation  of  warm  steam.  This  is  frequently 
impregnated  with  an  alkali,  like  lime,  or  with  some  mild  antiseptic 
agent,  like  eucalyptol,  the  compound  tincture  of  benzoin,  or  turpentine. 
But  it  is  the  steam  upon  which  the  chief  reliance  is  placed.  Oertel 
believes  that  the  energetic  use  of  hot  vapor  causes  a  rapid  and  abundant 
suppuration  of  the  diseased  tissue,  until  finally  the  pseudomem])ranous 
layer  becomes  completely  detached  from  the  rapidly  regenerating 
tissue  of  the  mucous  membrane,  and  is  expelled  either  piecemeal  or 
in  its  entirety.  He  regards  this  as  nature's  process  of  resolution  in 
favorable  cases. 

The  inhalation  of  warm  steam  is  undoubtedly  at  times  of  much 
benefit,  but  we  are  inclined  to  believe  that  this  treatment  is  often  carried 
to  excess.  When  shut  up  in  a  tightly  closed  tent  in  which  a  basin  of 
water  is  kept  constantly  boiling,  the  child  receives  not  only  a  diminished 
supply  of  oxygen,  when  the  blood  is  already  suffering  from  an  oxygen 
dearth,  but  his  skin  is  kept  bathed  in  moisture,  and  his  clothing  and 
bedding  are  constantly  damp.  The  effect  of  such  treatment  is  certainly 
depressing.  Warm  steam  inhalation  should  therefore  be  employed  with 
some  care.     Lennox  Browne  savs  that  the  bed  should  be  curtained 


710  DIPHTHERIA 

and  the  hot  vapor  "brought  near  it  by  means  of  a  steam-kettle,  but 
the  croup-tent  bed,  which  gives  the  httle  patient  a  continuous  vapor 
bath,  is  as  unnecessary  as  it  is  depressing." 

Slaking  Lime. — Inhalation  of  the  warm  vapor  which  arises  from 
slaldng  lime  in  water  has  been  highly  recommended  as  a  remedy  in 
membranous  croup.  The  vapor  thus  generated,  being  strongly  alkaline, 
is  believed  by  some  to  act  as  a  solvent  of  the  membrane.  Oertel  found 
that  when  a  piece  of  pseudomembrane  weighing  three  grains  was  placed 
in  lime-water  it  swelled  up  in  fifteen  or  twenty  minutes  into  a  loose, 
flaky  mass,  which  could  easily  be  divided,  and  after  from  thirty  to 
forty  minutes  was  completely  dissolved.  The  assumption  that  lime- 
water  acts  in  the  same  way  when  inhaled  in  the  forai  of  vapor  as  it  does 
in  the  test-tube  is  not,  we  think,  borne  out  by  experience.  At  any  rate 
this  treatment  is  not  so  frequently  employed  now  as  formerly. 

Calomel  Sublimation. — ^The  inhalation  of  sublimated  calomel  has 
been  extensively  used  for  the  last  twenty  years  or  more  with  some 
degree  of  success.  It  is  said  to  act  not  as  a  germicide,  but  by  hastening 
the  separation  of  the  pseudomembrane,  through,  possibly,  an  influence 
exerted  both  locally  and  constitutionally.  We  have  employed  it  fre- 
quently, but  with  only  indifferent  results.  The  number  of  cases  which 
were  materially  benefited  was  small.  The  method  of  using  it  is  very 
simple.  Place  the  child  in  an  improvised  tent,  not  so  large  but  that 
it  may  be  fairly  well  filled  with  the  fumes.  The  calomel  may  be  sub- 
limated by  placing  it  on  a  small  fire-shovel  containing  a  few  hot  coals; 
or  it  may  be  placed  on  a  red-hot  shovel,  or  on  a  piece  of  sheet  iron 
or  tin,  or  in  an  iron  spoon,  either  of  which  can  be  heated  by  means  of 
an  alcohol  lamp  or  a  Bunsen  burner.  Eight  or  ten  grains  should  be 
sublimated  every  hour,  or  at  longer  intervals. 

The  Internal  Use  of  Mercury. — The  internal  or  constitutional 
treatment  of  membranous  croup  is  to  be  carried  out  on  the  same  lines 
as  in  the  other  varieties  of  diphtheria.  Mercury  in  some  form  has 
long  been  employed,  and  most  physicians  believe  that  it  gives  better 
results  than  any  other  internal  remedy  that  has  been  recommended. 
Calomel  is  much  used  in  small  and  frequent  doses,  to  the  extent  of 
causing  slight  ptyalism.  Many  practitioners  confidently  expect  improve- 
ment as  soon  as  this  effect  is  produced.  Dr.  T.  Clarke  Miller,^  of 
Massillon,  Ohio,  expresses  great  confidence  in  mercuric  chloride  in 
the  treatment  of  all  forms  of  diphtheria.  He  gives  y  ^^  grain  of  calomel 
every  hour  for  twelve  to  twenty-four  hours,  and  then  continues  the 
same  dose  every  two  hours.  He  says:  "If  I  find  that  the  exudate  has 
originated  in  or  extended  to  the  larynx,  I  use  antitoxin  at  once.  If 
the  nose  is  involved  seriously,  it  is  well  to  use  antitoxin,  though  not 
to  the  exclusion  of  the  calomel.  I  would  omit  the  antitoxin  rather 
than  the  calomel."  The  bichloride,  cyanide,  and  iodide  of  mercury 
have  also  been  highly  recommended  by  some  writers. 

1  The  Diagnosis  and  Treatment  of  Diphtheria,  read  at  the  Toledo  Meeting  of  the  Ohio  State       ^ 
Pediatric  Society. 


THE  THEjVTMENT  OF  Dl I'llTII l<:iiIA  711 

It  is  a  pleasure  to  quote  so  often  an  author  whose  articles  on  rJiph- 
theria  are  everywhcTe  regarded  as  classic.  We  refer  to  Prof.  Jacobi, 
who  says:  "For  nearly  twenty  years  I  have  employed  the  bichloride 
in  doses  of  1  ingin.  (gr.  ,.,,)  or  more  once  every  hour.  The  smallest 
babies  take  one-fourth  or  one-third  of  a  grain  daily  for  days  in  succession. 
Almost  never  will  a  stomatitis  follow,  and  no  gastric  or  intestinal  irrita- 
tion, provided  the  dilution  be  in  the  proj)ortion  of  at  least  1:8000. 
An  occasional  slight  diarrlux'a  jnay  re((uire  the  addition  of  a  few  drops 
of  camphorated  tincture  of  opium.  1  can  repeat  a  fonner  statement, 
that  never  before  the  antitoxin  period  have  I  seen  cases  of  croup  getting 
well  in  such  numbers,  either  without  or  with  tracheotomy  or  intubation, 
as  when  under  mercurial  treatment."  We  have  already  expressed 
much  confidence  in  the  mercurial  treatment  of  diphtheria,  including, 
of  course,  membranous  croup. 

Operative  Measures. — If  it  be  found  that  the  laryngeal  symptoms 
do  not  improve  under  the  treatment  recommended,  but,  on  the  contrary, 
become  more  and  more  marked,  or  if  the  patient  be  not  seen  until 
the  symptoms  of  mechanical  obstruction  have  become  alarming,  recourse 
must  be  had  at  once  to  operative  measures.  The  operation  which  is 
necessary  to  overcome  the  difficulty  is  either  tracheotomy  or  intubation. 
Formerly  tracheotomy  was  universally  employed,  but  of  late  years 
it  has  been  almost  entirely  superseded,  in  this  country  particularly,  by 
intubation. 

Intubation.^ — This  procedure  is  viewed  more  favorably,  mainly 
because  it  does  not  require  the  use  of  the  surgeon's  knife.  We  all  know 
how  reluctantly  parents  give  their  consent  to  the  operation  of  trache- 
otomy on  their  child.  When  this  operation  was  the  only  means  of 
overcoming  the  obstruction  to  the  entrance  of  air  through  the  larynx, 
it  was  too  often  postponed  until  the  child  was  almost  moribund,  and, 
consequently,  the  results  were  discouraging.  Intubation  being  a  blood- 
less operation,  and  not  requiring  an  anaesthetic,  parents  do  not  hesitate 
to  give  their  consent  to  this  procedure,  and  hence  the  lives  of  many 
children  who  suffer  from  membranous  croup  are  now  saved  that  would 
otherwise  be  lost.  It  is  a  matter  of  great  importance  that  operative 
interference,  whether  intubation  or  tracheotomy,  be  not  delayed  too 
long.  It  is  almost  criminal  to  allow  a  child  to  die  from  suffocation 
without  making  an  effort  to  save  its  life  by  resorting  to  one  or  the  other 
of  these  mechanical  measures.  W^hile  intubation  is  to  be  preferred 
in  most  cases,  it  cannot  always  take  the  place  of  tracheotomj/.  A 
physician  without  experience  in  intubation  would  be  likely  to  fail  in 
the  operation,  and  if  no  one  possessing  the  necessary  skill  is  available, 
he  would  be  obliged  to  resort  to  tracheotomy.  Or  the  latter  operation 
may  be  preferred,  or  even  become  necessary,  when  the  membrane 
extends  far  down  into  the  trachea.  In  such  cases  the  intubation  tube 
will  not  afford  relief.  Tracheotomy  may  also  become  necessary  when 
the  intubation  tube  is  repeatedly  coughed  up. 

The  procedure  for  relieving  the  stenosis  of  membranous  croup  by 
placing  a  tube  in  the  larynx  with  its  upper  end  below  the  epiglottis 


712  DIPHTHERIA 

was  first  adopted  by  Bouchut  in  1858.  But,  as  his  devices  were  crude, 
and  as  the  operation  was  deemed  impracticable  by  his  confreres,  and 
even  ridiculed  by  them,  he  was  discouraged  from  pursuing  farther  his 
conception  of  intubation.  It  remained  for  Dr.  Joseph  O'Dwyer,  of  New 
York,  to  devise  and  perfect  the  instruments  necessary  for  the  operation, 
and  to  demonstrate  beyond  question  the  utility  of  the  procedure. 

O'Dwyer's  work  of  devising  the  intubation  tubes  was  begun  in  1880, 
without,  it  is  said,  any  knowledge  of  the  previous  experiments  of 
Bouchut.  It  required,  however,  some  four  or  five  years  of  diligent 
experimentation  before  the  set  of  intubation  instruments,  herein 
described,  was  evolved  into  its  present  state  of  perfection.  The  New 
York  Academy  of  Medicine  has  in  its  possession  a  complete  collection  of 
all  the  instruments  used  by  O'Dwyer  in  his  long  series  of  experiments. 
The  collection  is  interesting  as  showing  the  various  changes  in  the 
size,  shape,  and  construction  of  the  intubation  tube  in  its  evolutionary 
process. 

Intubation  Instruments. — In  their  completed  state  the  O'Dwyer 
intubation  instruments  consist  of  a  series  of  seven  tubes,  a  scale  for 
measuring  the  size  of  the  tubes,  an  obturator,  an  introducer,  a  mouth  gag, 
and  an  extractor.  The  tubes  vary  in  size,  both  as  to  their  calibre  and 
length,  so  as  to  fit  the  larynx  of  a  child  at  any  age.  Tubes  are  also 
made  suitable  for  adults,  though  they  do  not  form  a  part  of  the  regular 
outfit.  The  head  of  the  tube  is  irregularly  oval,  with  its  anterior  surface 
flush  with  the  tube  itself,  so  as  not  to  interfere  with  the  epiglottis,  while 
posteriorly  it  projects  backward  so  as  to  rest,  when  in  situ,  upon  the 
rima  glottidis.  A  tube  that  is  too  small  for  a  patient  may  slip  down 
into  the  trachea.  In  the  left  side  of  the  head  of  the  tube  there  is  a 
small  hole  into  which  a  string  may  be  inserted.  The  object  of  this 
string  is  that  the  tube  may  be  withdrawn  in  case  it  is  introduced  into 
the  oesophagus  instead  of  the  larynx.  The  circumference  of  the  tube 
is  somewhat  larger  in  its  centre.  The  anterior  and  posterior  surfaces 
of  the  tube  are  straight,  while  a  central  bulging  is  seen  on  either  side. 
This  is  called  the  "retaining  swell,'^'  as  it  helps  to  keep  the  tube  in 
place,  and  to  a  great  extent  prevents  its  expulsion  by  the  act  of  coughing. 
The  lower  end  of  the  tube  is  rounded  off  and  blunt,  and  its  lumen 
throughout  is  elliptic   (Fig.  99). 

The  tubes  were  originally  made  of  white  metal  plated  with  gold; 
but  later  the  inventor  had  them  constructed  of  hard  rubber  overlying 
metal.  This  is  considered  an  improvement,  as  the  tube  is  much  lighter, 
and  more  easily  coughed  out  when  the  lumen  becomes  occluded  with 
fragments  of  the  false  membrane.  It  is  believed,  too,  that  it  is  less 
liable  to  injure  the  larynx  when  worn  for  a  long  time.  Certainly,  it  is 
less  irritating  from  the  fact  that  lime  deposits  do  not  form  on  it,  as  on 
the  metal  tube.  The  latter,  when  worn  for  a  few  days,  is  quite  sure  to 
become  rough  from  these  deposits.  All  intubation  sets  made  at  the 
present  time  contain  only  hard-rubber  tubes. 

Each  tube  is  provided  with  an  obturator  which  is  fitted  to  the  intro- 
ducer.    The   obturator   extends   throughout   the   lumen   of  the   tube, 


Till':  Tli'l'JATMI'JA'T  OF  I )l I'll'I'llilUI A 


71i 


projectinfT  .sH^^Iitly  from  the  Iowcm-  cihI,  wIkwc  it  is  rouiHl<!(l  or  alrnorid- 
shapcd.  It  is  divided  into  two  jnirts,  joined  together  hy  ;i  fiin^c,  vvhirh 
makes  its  removal  easier  after  the  tube  has  been  initodiiccd  into  tlic 
larynx.  The  obtnrator  is  either  screwed  fast  to  the  inlrodiir-cr,  or  else 
it  forms  the  terniinal  part  of  a  lon<^  steel  rr)d  bent  at  a  ri^lit  an^lc,  aiul 
so  constructed  as  to  fit  the  introfhiccr.  The  hitter  const riid inn  r,!"  this 
instrument  is  now  preferred  by  most  operators  fl'if^.  100;. 


Fig,  99 


O'Dwyer's  intubation  instruments.    (After  Park.i 


The  introducer  is  designed  to  facihtate  the  introduction  of  the  tube. 
It  contains  the  o})turator,  and  is  provided  with  a  mechanical  device 
for  pushing  off  the  tube  after  it  has  been  placed  into  the  larynx. 

The  extractor  is  an  instrument  curved  at  one  end  so  as  to  form  almost 
an  angle  of  ninety  degrees,  terminating  in  a  beak-like  process  which  fits 
the  opening  in  the  tube.    Its  mechanical  design  is  such  that  by  pressing 


714 


DIPHTHERIA 


a  lever,  the  beak,  which  is  composed  of  two  parts,  separates.  When 
the  beak  is  introduced  into  the  hiinen  of  the  tube,  and  its  jaws  are 
separated  by  pressing  the  lever,  the  tube  is  grasped  in  such  a  way  as 
to  permit  of  its  extraction. 

The  mouth  gag  serves  the  purpose  of  keeping  the  patient's  jaws  apart 
during  the  operation  of  intubation  or  extubation. 

Short  Tubes. — Besides  the  tubes  described  above,  special  tubes 
have  been  devised  for  the  easy  expulsion  of  loose  membrane.  They 
are  short,  reaching  just  below  the  cricoid  cartilage.  They  are  cylindrical, 
and  have  no  retaining  swell.  Their  lumen  is  large  enough  to  permit 
pieces  of  detached  membrane  of  considerable  size  to  pass  through. 
These  tubes  are  believed  to  be  of  temporary  service  when  there  is  a 


Fig.  100 


Latest  design  of  intubation  instraments.    (After  Northrup 


good  deal  of  loose  membrane  in  the  trachea.    We  cannot  speak  of  their 
utility  from  personal  experience. 

Various  modifications  of  the  O'Dwyer  instruments  have  been  sug- 
gested from  time  to  time,  but  most  of  them  are  unnecessary  and  some 
worse  than  useless.  We  can  think  of  only  one  change  that  seems  worthy 
of  mention.  Seeing  that  operators,  especially  those  unskilled,  often 
find  it  difficult  to  remove  the  tube  from  the  larynx,  and  that  the  neighbor- 
ing soft  parts  are  frequently  injured  during  the  efforts  at  extraction, 
Dillon  Brown,  of  New  York,  was  led  to  modify  the  tube  and  devise  a 
different  extractor.  His  modification  consists  in  attaching  to  the  head 
of  the  tube  a  stiff  wire  loop  which  may  be  caught  by  the  extractor. 
The  latter  instrument  is  a  simple  hook  fastened  to  the  end  of  the  index 


77//';  TUl'JArM/'JNT  OF  1)1 1'llTII FIUA  715 

finger.  lie  (duiins  that  this  extractor  not  only  greatly  .simjjlific.s  the 
removal  of  tlio  tubc^  but  makes  it  iinj)ossihle  to  do  any  flarnaf^<;  to  the 
larynx  (hirii)<)^  this  procedure. 

When  this  device  was  first  brought  to  our  notice  we  gave  it  a  trial 
in  the  hospital,  but  it  did  not  prove  satisfactory.  It  is  true  that  an 
inexperienced  operator  usually  finds  it  diflicult  to  remove  th(;  tube 
with  the  O'Dwyer  extractor,  but  wlien  the  necessary  skill  has  been 
acquired  it  can  be  removed  readily  with  this  instrument,  and  withf^ut 
any  injury  to  the  larynx.  Northrup^  says:  "'J'he  extractor  perhaps 
has  called  forth  more  censure  than  the  other  instruments.  To  quote 
the  inventor:  'This  cannot  be  improved  upon  <'xcept  by  inventing 
an  instrument  which  will  find  the  hole  automatically.'  " 

The  Indications  for  Operative  Interference. — When  operative  inter- 
ference is  required,  intubation,  as  already  mentioned,  is  the  operation 
to  be  preferred.  But  whether  it  be  intubation  or  tracheotomy  the 
indications  for  operation  are  the  same.  If,  in  spite  of  the  treatment 
which  has  been  recommended  for  membranous  croup,  there  is  progres- 
sive asphyxia,  as  evidenced  by  increasing  dyspncea,  labored  breathing, 
stridor,  suppression  of  voice,  cyanosis,  retrocession  of  the  supraclavicular 
fosste,  as  well  as  of  the  epigastrium  and  the  lower  ribs,  the  operative 
procedure  should  not  be  delayed. 

Intubation  is  not  so  simple  an  operation  as  to  be  resorted  to  indis- 
criminately. When  introduced,  the  tube  acts,  of  course,  as  a  foreign  body 
in  the  larynx  and  is  not  incapable  of  doing  harm.  To  say  nothing  of 
the  slight  abrasion  that  may  result  from  its  introduction,  even  by  skilled 
hands,  its  presence  in  the  larynx  for  several  days  is  liable  to  cause 
ulceration  at  the  points  where  it  impinges.  But,  notwithstanding  this 
fact,  when  the  indications  for  intubation  are  clear  and  unmistakable 
it  should  be  performed  at  once.  Do  not  wait  until  the  pulse  begins 
to  flag  and  the  child's  strength  becomes  exhausted,  else  death  may 
suddenly  occur  from  heart-failure.  We  repeat  that  when  there  is  a 
marked  retrocession  of  the  epigastrium  at  each  inspiratory  act,  and 
cyanosis  is  evident,  intubation  should  not  be  delayed  another  moment. 
By  waiting  longer  nothing  but  harm  can  come  to  the  lungs  and  to  the  heart. 

The  Technique  of  Intubation. — No  anaesthetic  is  recjuired  for  this 
operation,  but  it  is  necessary  that  the  child  should  be  brought  under 
perfect  control.  This  may  be  accomplished  by  placing  the  child's 
arms  downward  in  a  straight  line  with  the  body  and  rolling  him  up 
in  a  sheet  or  light  blanket.  In  thus  preparing  the  child  care  should 
be  taken  to  avoid  having  too  great  a  bulk  of  the  blanket  on  the  chest 
of  the  child,  as  this  will  interfere  with  the  manipulations  of  the  operator. 
The  child  should  then  be  placed  on  the  lap  of  a  nurse  seated  in  a  chair, 
with  its  head  somewhat  above  her  left  shoulder.  She  should  grasp  the 
child  in  her  arms,  and  hold  its  legs  firmly  between  her  knees.  (See 
Fig.  101.)  The  child  is  thus  brought  under  complete  control,  with  no 
great  increase  to  its  discomfort. 

1  Nothuagel's  Encyclopedia  of  Practical  Medicine,  American  edition. 


716 


DIPHTHERIA 


The  gag  should  now  be  placed  between  the  jaws  of  the  child  on  the 
left  side,  and  held  by  the  assisting  physician  or  nurse,  who,  standing 
behind  the  child,  steadies  also  its  head  with  a  firm  grasp  of  his  hands. 
It  is  assumed,  of  course,  that  the  operator  has  already  selected  the  tube 
suited  to  the  age- of  the  child,  that  he  has  inserted  into  the  eyelet  of  the 
tube  a  silk  ligature  or  string,  which,  when  both  ends  are  tied  together, 
is  long  enough  to  reach  nearly  to  the  end  of  the  handle  of  the  introducer, 
and  that  he  has  affixed  the  obturator  with  its  tube  to  the  introducer. 
It  is  advisable  to  see  that  his  instruments  work  well  by  pushing  the 
tube  off  of  the  obturator  once  or  twice  before  beginning  the  operation. 


Showing  the  first  steps  of  imubation  in  the  upright  position. 

PAX  preliminary  arrangements  being  completed,  the  operator,  sitting 
or  standing,  as  he  may  prefer,  in  front  of  the  patient,  inserts  his  left 
index  finger  and  feels  for  the  epiglottis.  Having  secured  it,  he  pulls 
it  forward  on  the  base  of  the  tongue,  keeping  his  finger  as  much  to  the 
left  as  possible.  With  the  introducer  in  his  other  hand,  he  passes  the 
tube  over  the  dorsum  of  the  tongue  until  it  reaches  the  chink  of  the 
glottis,  when  the  handle  of  the  introducer  should  be  quickly  raised  so 
that  the  tube  may  pass  downward  into  the  larynx.  It  should  then  be 
pushed  off  and  the  obturator  withdrawn,  the  tip  of  the  finger  mean- 
while being  held  on  the  head  of  the  tube  to  prevent  its  being  pulled 
out.  The  operator  should  not  let  go  the  string  until  he  is  sure  the  tube 
is  in  the  larynx.    Its  presence  in  the  larynx  is  known  by  the  shrill  m.etallic 


77//';  ti{I<:atmi<:nt  of  dii'ii'i'iikih  \  717 

cough,  and  by  the  rehfif  of  the  dyspnd'a.  If  the  tuh(^  has  h(?cn  iritrofJueed 
into  the  oesophagus  there  is,  of  course;,  no  relief.  This  lf>eation  of  the 
tube  may  also  be  recognized  by  the  fact  that  the  string  grows  shorter 
as  the  tube  descends  into  tlie  o'sophagus.  It  should  Ix-  pulh-fJ  oni  at 
once. 

'^rhe  tube  being  properly  placed,  it  is  well  to  remove  the  mouth  gag 
and  allow  the  child  to  cough  and  expectorate  for  a  minute  or  two,  anrl 
at  the  same  time  to  be  sure  that  there  is  no  obstruction  in  tlic  tube 
Everything  being  satisfactory  the  gag  should  be  reintroduced,  the 
string  cut  and  withdrawn,  while  the;  tip  of  the  index  finger  rests  on 
the  head  of  the  tube  to  prevent  its  displacement.  'J"'he  child  should  then 
be  released  and  put  to  bed. 

If  the  child  is  very  young,  having  no  molar  teeth,  and  the  operatfjr 
distrusts  his  ability  to  remove  the  tube  with  the  extractor,  the  string, 
instead  of  being  cut  and  withdrawn,  may  })e  looped  over  the  ear  of 
the  child  and  secured  to  the  cheek  with  a  strip  of  adhesive  plaster.  In 
this  case  the  hands  of  the  child  must  be  muffled,  else  the  offending 
string  will  be  caught  with  the  fingers  and  the  tube  pulled  out.  In 
children  with  teeth  this  procedure  is  not  to  be  recommended,  as  the 
string  is  soon  chewed  off  and  rendered  useless.  Experienced  operators, 
however,  prefer  to  remove  the  string  in  all  cases. 

There  are  still  some  other  points  in  connection  with  the  operation 
that  the  beginner  should  know.  In  the  first  step  of  the  operation  the 
operator's  hand  containing  the  introducer  should  be  close  to  the  chest 
of  the  patient.  The  tube  should  be  pushed  backward  on  the  median 
line  of  the  tongue  until  it  reaches  the  chink  of  the  glottis,  then  the 
handle  of  the  instrument  must  be  raised,  and  the  tube  should  slip 
down  into  the  larynx  without  much  force  being  used.  The  tube,  during 
its  introduction,  sometimes  causes  a  slight  spasm  of  the  parts,  in  which 
case  the  operator  should  pause  for  a  few  moments,  when  the  spasm 
will  probably  relax  and  the  tube  slip  into  place.  It  should  be  remem- 
bered that  the  epiglottis  must  be  kept  out  of  the  way;  if  not  the  operation 
will  surely  fail.  It  is  important,  too,  that  the  child  should  be  under 
perfect  control  in  the  arms  of  the  nurse,  and  that  it  should  squarely 
face  the  operator.  The  position  of  the  child's  head  and  neck  should 
be,  as  Northrup  says,  as  if  the  child  were  suspended  from  the  top  of 
its  head. 

In  case  the  first  attempt  at  placing  the  tube  is  unsuccessful,  rather 
than  exhaust  the  patient  with  repeated  trials  at  one  sitting  it  is  better 
to  remove  the  gag  and  allow  the  child  a  few  seconds  to  rest,  or  to  cough 
and  expectorate.  A  beginner  rarely  succeeds  the  first  time;  it  is  far 
better  that  he  should  make  several  short  attempts  than  a  prolonged 
one. 

A  vigorous  cough  following  the  introduction  of  the  tube  is  favorable 
rather  than  otherwise,  as  it  shows  that  the  parts  have  not  lost  their 
sensitiveness,  and  it  clears  the  mucus  from  the  trachea.  If  there  is 
no  cough,  and  the  breathing  ceases  and  the  cyanosis  deepens,  there  is 
surely  an  obstruction  at  the  lower  end  of  the  tube;  in  which  case  it 


718 


DIPHTHERIA 


should  be  removed  immediately.    If  the  same  result  follows  a  repetition 
of  the  operation,  tracheotomy  should  be  performed. 

Some  operators  prefer  to  have  the  child  in  the  recumbent  position 
during  the  act  of  intubation.  The  advantages  claimed  for  this  position 
are  that  the  operation  can  be  performed  with  but  a  single  assistant, 
and  that  there  is  less  danger  of  heart-failure  if  the  patient  be  greatly 
prostrated.  The  child  should  be  rolled  up  in  a  sheet  or  thin  blanket, 
as  already  described,  and  placed  squarely  on  its  back.  (See  Fig.  102.) 
In  other  respects  the  operator  should  proceed  as  before.  At  the  present 
time  the  resident  physicians  in  the  Municipal  Hospital  employ  this 
method  altogether.     It  is  also  employed  in  the  Willard  Parker  Hos- 


FlG.  102 


Showing  the  lirst  steps  of  intubation  in  the  dorsal  position. 
Dr.  B.  Franklin  Royer.) 


(Photograplied  by 


pital,  New  York,  and  is  recommended  by  Casselberry,  of  Chicago,  and 
Carstens,  of  Leipzig. 

Dangers  and  Difficulties  of  Intubation. — The  operation  cannot  be 
said  to  be  dangerous  when  performed  by  an  experienced  operator. 
It  is  true,  instances  have  occurred  in  which  exudate  has  been  pushed 
down  into  the  trachea  by  the  tube,  causing  suffocation  and  instant 
death.  This  condition,  however,  is  easily  recognized  at  once,  and  the 
prompt  removal  of  the  tube  is  usually  followed  by  forcible  expulsion 
of  the  detached  mass  of  false  membrane.  When  this  occurs  the  dyspnoea 
may  be  so  greatly  relieved  that  reintubation  is  not  necessary.  But  fre- 
quently the  membrane  reforms  and  the  operation  is  again  called  for. 


77//';  TIU<L\rMI<:NT  OF  l)ll'IITIII<:i{lA 


719 


Under  the  circumstances  just  mentioned,  we  would  (;mphasize  the 
importance  of  removing  the  tube  promptly;  for  if  tliere  is  tof>  much 
delay  the  sensitiveness  of  the  parts  soon  becomes  so  blunted  that  cough, 


Fk;.  103 


Fixation  of  the  larynx.   (Lejars. ) 
Fig.  104 


The  tube  guided  by  the  index  linger.    (Lejars.) 


on  which  the  safety  of  the  patient  depends,  is  not  excited,  and  death 
speedily  results  from  suffocation. 

The  inexperienced  and  clumsy  operator  may  incur  other  dangers,  such 
as   asphyxia  from   prolonged   attempts   at  intubation,   lacerating  the 


720 


DIPHTHERIA 


tissues,  or  forcing  the  tube  into  a  false  passage.     All  of  these  accidents 
can  be  avoided  with  care. 

There  are  but  few  serious  difficulties  liable  to  be  encountered  by 
the   experienced   operator.      It   has   been  said   that  the  tube  may  be 


Fig.  105 


The  tube  penetrates  the  larynx.    (Lejars.) 
Fig.  106. 


The  tube  in  its  proper  position .    CLejars.) 


obstructed  m  its  course  by  entering  one  of  the  ventricles  of  the  larynx. 
This,  we  are  sure,  hardly  ever  happens  Avith  the  O'Dwyer  tubes  which 
are  so  nicely  rounded  at  their  ends.  Besides  the  pushing  down  of 
membrane  before  the  tube,  or  the  occurrence  of  a  slight  spasm  of  the 


TIIF.  TltKATMNNT  OF  1)1 1'llTII I'llil A 


721 


muscles  of  the  larynx,  as  dcscrihcd  alxjvc,  in  inlrofliir-Irif^  tlif  tnljc  the 
operator  will  soinetinics  meet  with  (h"(licnlty  caused  hy  swelHn^',  inflam- 
matory thickening,  or  anlema  of  the  subglottic  tissues.  \Vh(;ri  it  is 
found  that  the  tube  adapted  to  the  age  of  the  child  will  n(jt  enter  readily, 
it  is  advisable  to  try  a  smaller  one.  After  this  has  been  worn  for  a 
short  time  there  is  usually  no  difficulty  in  introducing  (me  of  tiie  j)roper 
size.  The  narrowest  part  of  the  lumen  of  the  larynx  is  in  the  region 
of  the  cricoid  cartilage.  We  have  seen  a  few  instances  in  girls  in  which 
the  cricoid  ring  was  abnormally  small,  a  fact  which  we  have  been  able 
to  demonstrate  post-mortem,.  When  this  condition  exists  only  a  little 
sweUing  or  a^dema  of  the  lining  membrane  is  needed  to  ninkc  the  intro- 


Withdrawal  of  the  thread.    (Lejars.) 


duction  of  the  tube  difficult.  The  only  thing  to  do  in  such  cases  is  to 
use  a  smaller  tube. 

Treatment  and  Feeding  After  Intubation. — It  is  advisal^le  not  to 
make  any  local  applications  to  the  throat  while  the  tube  is  in  the  lar^iix; 
at  least,  irrigation  or  spraying  should  not  be  practised.  The  applications 
to  the  nose,  if  required,  need  not  be  omitted.  Internal  treatmeat, 
stimulants,  and  the  like,  may  be  continued  as  before. 

The  feeding  of  the  child  is  the  thing  that  frequently  gives  us  the  most 
concern.  Some  children  swallow  with  but  little  difficulty  after  intuba- 
tion, while  it  is  really  distressing  to  see  others  drinking  liquids  of  any 
kind.  The  act  of  swallowing  excites  coughing,  and  this  may  be  still 
further  excited  by  some  of  the  liquid  running  down  the  tube  into  the 

^  46 


722 


DIPHTHERIA 


trachea.  The  cough  is  often  violent,  causing  a  large  part  of  the  liquid 
in  each  act  of  swallowing  to  be  forcibly  expelled,  not  only  through  the 
mouth  but  through  the  nose  also.  Children,  however,  usually  persevere 
in  drinking,  and  after  a  little  while  they  frequently  get  along  better. 
Semisolid  food  is  not  so  liable  to  cause  coughing,  and  is,  therefore, 
preferable.  When  a  child  is  old  enough,  we  prefer  to  have  it  fed  on 
bread  soaked  in  milk.  This  forms  a  bolus  which  can  be  swallowed, 
as  a  rule,  without  exciting  much  cough. 

Fig.  108 


Casselberry's  position  for  feeding  intubated  cases.    (After  Nortlirup.) 

It  is  claimed  that  the  difficulty  of  swallowing,  even  of  liquids,  may 
be  overcome  by  placing  the  child  on  its  back  with  the  body  and  legs 
elevated,  while  the  head  hangs  over  backward  at  an  angle  of  forty-five 
degrees  or  greater.  It  is  thought  that  any  liquid  that  may  get  into  the 
tube  will,  with  the  child  in  this  position,  run  out  again  rather  than  into 
the  trachea.  The  placing  of  the  child  in  this  position  during  feeding  was 
first  recommended  by  Casselberry,  of  Chicago.  He  and  many  other 
physicians  who  have  tried  this  method  speak  of  it  very  favorably.  In 
our  experience  it  has  not  proved  so  satisfactory.     In  bottle-fed  babies 


77//';  TRMATMIiNT  Oh'lDII'UTII l-:i{IA  723 

it  sometimes  answers  fairly  well.  It  should  ])C  stated  that  soirie  [jhysieians 
believe  that  the  child  swallows  b('tt<'r  lyin^  on  the;  abdomen  with  the 
head  hanging  forward. 

If  it  be  found  that  the  child  is  not  getting  sufficient  nourishm(;nt  by 
either  of  the  methods  mentioned,  gavagi;  should  be  resorted  to.  This 
may  be  done  by  introducing  either  a  small  o'sophageal  tube  or  a  flexible 
catheter  through  the  nose  into  the  stomach.  If  this  route  is  found 
inconvenient  or  dilficult,  the  child's  jaws  may  be  slightly  separated 
and  the  tube  introduced  through  the  mouth.  If  one  catheter  should 
not  be  long  enough  another  may  be  joined  to  it  by  means  of  a  short 
glass  tube.  Some  prefer  rectal  feeding,  but  v^'e  have  never  found  it. 
satisfactory. 

Removal  of  the  Tube,  or  Extubation. — The  time  for  remo^'ing  the 
tube  will  depend  very  much  on  the  age  of  the  child  and  the  stage  of  the 
disease.  In  older  cliildren  the  tube  may  be  removed  earlier  than  in 
those  who  are  younger.  Likewise,  when  the  tube  is  not  required  until 
a  late  stage  of  diphtheria,  it  may  l)e  removed  sooner  than  when  intro- 
duced at  an  early  stage  of  the  disease.  We  have  seen  it  stated  some- 
where that  O'Dwyer  recommended  that  the  average  time  of  wearing 
the  tube  should  be  seven  days;  and  if  the  patient's  residence  is  a  long 
distance  from  the  physician's  office  the  time  had  better  be  eight  days. 
It  has  been  our  rule  to  allow  the  tube  to  remain  in  place  six  days  before 
removing  it.  Frequently,  however,  the  resident  physicians  remove  it 
earlier,  but  they  often  find  it  necessary  to  reintroduce  it.  Northrup 
thinks  that  five  days  for  a  child  over  two  years  is  long  enough  for  the 
tube  to  be  worn  in  the  average  case.  He  says:  "At  the  Willard  Parker 
Hospital  the  time  allowed  is  four  days;  at  the  New  York  Foundling 
Hospital,  three  days."  He,  with  many  other  writers,  believes  that  the 
length  of  time  which  the  tube  is  required  in  membranous  croup  has 
been  materially  reduced  by  the  use  of  antitoxin;  also,  that  reintubation 
is  now  less  often  required. 

Cases  are  not  infrequently  seen  in  which  the  tube,  after  having  been 
worn  for  only  a  short  time,  is  coughed  up  and  expelled,  together  with  a 
mass  of  membrane.  Such  cases  sometimes  recover  without  reintubation 
being  required.  There  are  other  cases  in  which  the  tube  is  not  retained 
longer  than  it  is  needed;  that  is  to  say,  in  the  course  of  four  or  five  days, 
when  the  membrane  in  the  larynx  has  disappeared  and  the  oedema  sub- 
sided, autoextubation  takes  place  through  the  agency  of  the  cough.  This 
result  is  always  gratifying,  and  especially  so  to  the  inexperienced  operator. 

Whenever  the  tube  becomes  obstructed  it  must,  of  course,  be  instantly 
removed.  Fortunately,  in  most  cases  it  is  coughed  up.  Wlien  coughed 
up,  the  tube  is  either  expelled  or  the  child  removes  it  from  the  mouth 
with  his  fingers.  In  rare  instances  it  is  swallowed.  Should  this  occur, 
no  great  uneasiness  need  be  felt,  as  we  have  never  known  a  tube  that 
was  swallowed  fail  to  pass  through  the  intestines. 

The  Technique  of  Extubation. — Up  to  a  certain  point  the  technique 
of  the  operation  of  extubation  is  exactly  the  same  as  that  of  intubation. 
After  being  rolled  up  in  a  blanket  or  sheet,  as  before,  the  child  should 


724  DIPHTHERIA 

be  held  in  the  upright  position  on  the  lap  of  the  nurse,  or  placed  in  the 
dorsal  position,  according  to  the  choice  of  the  operator.  It  is  equally 
important  that  the  child's  head  should  be  held  steady,  and  that  the 
axis  of  the  head,  neck,  and  trunk  should  correspond.  The  mouth  gag 
being  in  position,  the  operator  passes  his  index  finger  of  the  left  hand 
backward  over  the  dorsum  of  the  tongue  until  he  feels  the  tube  and 
determines  its  position.  He  should  then  tilt  the  epiglottis  forward  and 
control  it.  Holding  the  extractor  in  his  right  hand,  with  the  handle 
of  the  instrument  near  the  chest  of  the  child,  he  should  pass  it  backward 
along  the  side  of  the  finger  until  the  tube  is  reached;  the  handle  of  the 
extractor  should  then  be  raised  to  a  horizontal  position,  and,  with  the 
aid  of  the  tip  of  the  finger  which  is  controlling  the  epiglottis,  he  inserts 
the  beak  of  the  instrument  into  the  opening  of  the  tube.  Having  suc- 
ceeded in  doing  this,  he  presses  down  the  lever  at  the  upper  part  of 
the  extractor  with  his  thumb,  which  causes  the  two  parts  of  the  beak 
of  the  instrument  to  separate,  and  thus  the  tube  is  caught  and  held, 
very  much  as  a  glove  stretcher  holds  the  finger  of  a  glove.  The  operation 
is  completed  by  lifting  the  extractor  with  the  tube  until  it  impinges  on 
the  hard  palate,  then  depressing  the  handle  and  withdrawing  the 
instrument  and  tube  from  the  mouth.  If  the  tube  should  slip  off,  as  it 
often  does,  after  having  been  lifted  from  the  larynx,  its  removal  can 
easily  be  concluded  by  means  of  the  finger. 

It  is  important  to  properly  regulate  the  distance  of  separation  of 
the  two  parts  of  the  beak  of  the  extractor.  This  may  be  done  by 
means  of  the  screw  in  the  handle.  If  the  jaws  of  the  instrument  are 
allowed  to  open  too  widely  the  orifice  of  the  larynx  may  be  lacerated 
by  a  clumsy  operator.  Tlie  extractor  should  be  held  in  the  hand  lightly, 
as  no  great  force  is  required  to  remove  the  tube.  Be  careful  not  to 
place  the  thumb  on  the  lever  until  the  beak  of  the  instrument  is  well 
within  the  opening  of  the  tube. 

If  the  operator  should  have  difficulty  in  grasping  the  tube,  it  is  better 
to  make  repeated  short  attempts,  allowing  the  child  to  rest  for  a  minute 
or  two  in  the  intervals,  than  to  make  a  single  prolonged  effort.  As 
extubation  is  more  difficult  than  intubation,  beginners  often  become 
nonplussed  in  their  efforts  to  extract  the  tube.  In  such  a  dilemma, 
enucleation,  or  removal  by  pressure,  is  recommended.  Park^  says: 
"  It  is  possible  in  an  emergency,  in  the  majority  of  cases,  to  easily  expel 
the  tube  by  placing  the  child  face  downward  with  the  body  slightly 
elevated,  and  pressing  gently  against  the  trachea  along  its  anterior 
surface,  just  below  the  end  of  the  intubation  tube."  One  of  the  writers 
tried  this  expedient  a  few  years  ago,  but  did  not  succeed.  It  was  feared 
that  the  amount  of  pressure  required  to  accomplish  the  purpose  might 
injure  the  larynx. 

After  the  tube  has  been  removed  the  patient  should  be  placed  in  bed 
and  carefully  watched  for  a  while  to  see  that  the  respirations  continue 
easy.    In  family  practice  the  physician  should  not  leave  the  house  for 

1  Loomis-Thompson,  American  System  of  Practical  Medicine. 


r///';  trmatmi<:nt  of  dii'IitiiI'Uua  725 

at  least  thirty  minutes.  Tf  tlu'rc  is  any  Hifliculty  in  })r('afliinf(  lio  sliouM 
remain  until  lie  feels  reasonably  sure  that  tin;  jjaticnt  is  going  to  get 
along  without  the  tube.  Reintubation  is  often  necessary.  When  dyspncjea 
returns  after  extubation  the  condition  of  the  patient  not  infrequently 
becomes  critical  so  (juickly  that  if  })rompt  aid  be  not  afforded  fleatli 
from  suffocation  will  siu'ely  result.  It  is,  therefore,  highly  im[>fjrfant 
that  the  physician  should  be  within  easy  call  ff)r  some  hours.  Having 
seen  not  a  few  children  perish  at  this  stage  of  the  disease  when  their 
lives  might  have  been  saved  by  prompt  aid,  we  feel  that  the  importance 
of  the  advice  just  given  cannot  be  emphasized  too  strongly.  To  lose 
a  child  (hu-ing  the  height  of  an  attack  of  membranous  frr)up  is  bad 
enough,  but  to  see  it  die  after  the  danger  has  apparently  passed,  and  when 
the  brightest  hopes  are  entertained  for  its  recovery,  is  much  worse. 
Such  a  result  may  not  inaptly  be  compared  to  the  sinking  of  a  ship  in 
the  harbor  after  it  has  weathered  the  storms  of  the  ocean. 

For  lessening  the  nervous  excitability  of  the  patient,  as  well  as  for 
its  relaxing  effect,  a  little  morphine  may  be  given  just  before  removing 
the  tube.  Park  says  that  at  the  Willard  Parker  Hospital,  "immediately 
after  the  extraction  of  the  tube,  the  child  is  given  -^^  grain  of  morphine 
hypodermically,  and  an  ice-bag  is  applied  to  the  larynx.  It  is  sought 
in  this  way  to  lessen  the  irritation  and  swelling  of  the  larynx.  The 
child  is  still  kept  in  a  recumbent  position  for  one  or  two  days."  Perfect 
quietness  at  this  time  is  of  great  importance.  A  few  hours  of  quiet 
sleep  after  extubation  is  quite  desirable,  as  it  will  sometimes  tide  a 
patient  over  the  period  at  which  the  indications  for  reintubation  are 
most  likely  to  develop. 

Prolonged  Intubation. — Despite  the  free  use  of  antitoxin,  and  the 
greatest  possible  care  in  the  operation  of  intubation  and  extubation, 
it  frequently  happens  that  the  tube  must  be  w^orn  for  a  much  longer 
period  than  five  or  six  days.  In  other  words,  when  the  tube  is  removed 
at  the  time  just  indicated,  the  dyspnoea  returns,  making  reintubation 
necessary;  and  this  sometimes  happens  over  and  over  again  in  the 
same  patient  through  a  long  series  of  intubations  and  extubations. 
We  know  of  nothing  connected  with  the  work  of  intubation  that  is 
more  perplexing  to  the  operator,  or  more  distressing  to  the  patient, 
than  this  unfortunate  occurrence.  Some  of  these  cases  require  months 
and  in  rare  instances  years  of  intubating  until  recovery  takes  place. 
Indeed,  a  large  proportion  of  the  most  obstinate  cases  perish  from  one 
cause  or  another  before  the  difficulty  is  overcome. 

Prolonged  intubation  is  not  always  due  to  the  same  cause;  it  may 
result  from  one  of  several  causes,  such  as  persistence  of  the  false  mem- 
brane in  the  larynx,  oedema  of  the  tissues,  subglottic  lar}Tigitis  with 
thickening  of  the  soft  parts,  ulcerations,  exuberant  granulations,  cica- 
tricial contractions,  destruction  of  the  cartilages  and  collapse  of  the 
larynx,  atony  of  certain  muscles,  or  abductor  paralysis.  But  it  must  be 
admitted  that  it  is  often  difficult  to  differentiate  between  these  various 
pathological  conditions  of  the  larjTix,  or  to  explain  satisfactorily  the 
exact  cause  of  the  difficulty. 


726 


DIPHTHERIA 


Fig.  109 


Some  writers  believe  that  the  conditions  rendering  the  prolonged 
use  of  the  tube  necessary  are  rare,  or  even  extremely  infrequent.  We 
have  met  with  very  many  cases  in  which  it  was  necessary  to  continue 
the  use  of  the  tube  longer  than  the  usual  period  of  five  or  six 
days  without  development  of  the  pathological  changes  which  lead  to 
chronic  stenosis.  Such  cases  are  able  to  get  along  without  the  tube 
in  the  course  of  two  weeks,  or  three,  at  the  longest. 
But  postdiphtheritic  stenosis  occurs,  according  to 
our  experience,  in  from  1  to  3  per  cent,  of  all 
cases  of  intubation.  Dillon  Brown  is  reported 
as  saying  that  he  has  encountered  it  in  the  pro- 
portion of  about  once  in  75  or  100  cases. 

In  discussing  the  causes  of  prolonged  intuba- 
tion but  little  consideration  need  be  given  to 
traumatism  resulting  from  the  introduction  or 
removal  of  the  tube.  While  it  is  true  that  the 
unskilful  use  of  the  introducer  or  extractor,  or 
too  much  pulling  upon  the  epiglottis  during  the 
operation,  may  cause  abrasions  and  oedema  of 
the  soft  parts,  and  thus  make  reintubation  neces- 
sary, yet  it  is  certain  that  the  principal  cause  of 
"retained  tubes"  is  not  due  to  such  an  injury,  but 
to  traumatism  in  the  larynx  occasioned  by  the  tube 
itself.  It  is  important  that  the  tube  should  prop- 
erly fit  the  larynx;  it  certainly  should  not  be  too 
large.  But  no  matter  how  well  it  fits,  it  some- 
times causes  ulceration.  It  should,  therefore,  be 
dispensed  with  as  soon  as  possible.  It,  however,  should  not  be  removed 
until  there  is  reason  to  believe  the  patient  can  get  along  without  it;  for 
removing  it  too  early  would  necessitate  its  reintroduction,  and  thus  the 
risk  of  traumatism  would  be  increased. 

When  the  tube  is  required  longer  than  the  usual  length  of  time  on 
account  of  the  persistence  of  false  membrane  in  the  larynx,  the  con- 
dition, from  our  present  point  of  view,  is  not  serious,  for  as  soon  as 
the  membrane  disappears  the  tube  can  be  dispensed  with. 

We  believe  that  the  most  common  cause  for  retention  of  the  tube, 
at  least  primarily,  is  subglottic  laryngitis  with  oedema.  Later,  as  the 
tube  is  worn  longer,  and  has  been  removed  and  reintroduced  many 
times,  tissue  changes  of  a  destructive  character  sometimes  take  place 
in  the  larynx,  with  a  marked  tendency  to  terminate  in  chronic  stenosis. 
We  have  removed,  post-mortem,  larynges  which  showed  considerable 
loss  of  tissue  from  ulcerative  action.  These  ulcers  heal  by  granulation 
and  the  formation  of  cicatricial  tissue,  and  hence  permanent  stenosis 
to  a  greater  or  less  degree  is  liable  to  result  in  such  cases. 

Many  of  the  cases  with  subglottic  laryngitis  and  oedema  improve 
after  two  or  three  intubations,  and  recovery  follows  without  any  un- 
toward symptoms.  Other  cases  are  more  troublesome,  especially  those 
which  develop  also  atony  of  the  muscles  or  abductor  paralysis.    With 


Pressure  ulcer  due  to  intu- 
bation.  (Baginsky.) 


PLATE    LIX. 


Larynx  and  Trachea  Renioved  at  Autopsy. 

Sho'v\nng  a  large   roundisli  ulcer  caused   by  pressure  of  the   intubation  tube. 
The  lower  linear  -wound   -was  the  result  of  a  tracheotomy.      From  a  patient  in 

the  Municipal  Hospital.      (Photographed   by  Dr.   E.    N".    Fought.) 


77//';  r/U'JATMJ'JNT  OF  1)1 1'lmi Hiu A  727 

this  complication  it  may  be  necessary  to  repeat  intubation  many  times, 
and  the  patient  is  fortnnate  if  he  escapes  ulceration  of  the  larynx.  He, 
however,  rarely  escapes  bronchopneumonia,  more  or  less  marked. 

When  there  is  marked  ulceration  of  any  part  of  the  larynx,  with 
little  or  no  oedema,  the  child  may  get  along  fairly  well  witliout  the  tube 
for  a  few  days,  but  as  cicatrization  takes  place  the  lumen  of  the  larynx 
becomes  gradually  diminislied,  with  a  correspondingincrease  of  dyspna-a. 
In  attempting  to  perform  intubation  in  such  a  case,  it  has  been  found 
impossible  to  introduce  the  tube.  We  have  been  confronted  with  this 
difficulty  more  than  once,  and  in  order  to  save  the  child's  life  have 
resorted  to  tracheotomy. 

In  cases  of  ulceration  of  the  larynx  we  believe  it  is  good  practice  to  use 
the  tube  intermittingly  until  the  ulcers  have  cicatrized.  If  there  is  difficulty 
in  introducing  the  tube  it  had  better  be  left  undisturbed  for  a  long  time 
— i.  e.,  from  one  to  two  weeks  at  least.  In  cicatricial  stenosis,  however, 
after  the  difficulty  is  overcome  of  introducing  a  tube,  though  small, 
but  of  sufficient  calibre  to  supply  the  lungs  with  air,  it  is  comparatively 
easy,  after  this  tube  has  been  worn  for  a  day  or  two,  to  introduce  a 
larger  one.  Having  thus  restored  the  normal  lumen  of  the  larynx,  it 
is  advisable  to  insert  the  tube  two  or  three  times  a  week  for  a  while, 
leaving  it  in  place  from  twelve  to  twenty-four  hours.  Later,  as  the 
conditions  improve,  it  need  not  be  introduced  so  frequently.  But  the 
tube  should  not  be  dispensed  with  until  the  tendency  to  recontraction 
of  the  cicatricial  tissue  has  been  overcome. 

In  cases  of  prolonged  intubation  the  vulcanite  tube  should  by  all 
means  be  preferred.  The  calcareous  deposits  which  always  form  on 
metallic  tubes  make  them  very  objectionable.  They  cannot  be  worn 
long  without  causing  irritation  and  often  ulceration  of  the  larynx.  As 
these  deposits  do  not  form  on  hard-rubber  tubes,  they  may  be  allowed 
to  remain  in  position  for  a  long  time  without  doing  harm.  One  of  our 
cases  of  four  years'  standing  has  worn  a  vulcanite  tube  continuously 
for  periods  of  three  months  each,  and  once  as  long  as  five  months 
without  removal,  with  no  unpleasant  consequence  except,  as  the  parents 
say,  an  offensive  breath.  The  tube  never  showed  any  calcareous 
deposits.  It  is  worthy  of  remark  that  when  the  tube  has  been  worn 
for  a  long  time  the  child  acquires  the  ability  to  swallow  with  little  or 
no  difficulty. 

We  have  called  attention  to  the  fact  that  in  some  cases  of  prolonged 
intubation,  after  the  tube  has  been  removed  for  a  few  days,  it  is  impossible 
to  reintroduce  it,  and  that  tracheotomi/  becomes  necessary.  Likewise, 
this  operation  may  be  deemed  expedient  when  the  tube  cannot  be 
retained  in  position.  We  have  seen  cases  in  which  the  tube  was  con- 
stantly coughed  up,  even  when  it  was  two  or  three  sizes  too  large.  In 
such  a  case  it  sometimes  happens  that  the  head  of  the  tube  enters  the 
postnasal  space  and  suffocation  threatens  if  the  tube  be  not  immedi- 
ately removed  or  pushed  down  into  the  larjTix.  To  keep  it  in  place 
would  require  a  constant  attendant.  Under  such  circumstances  it  is 
better  to  perform  tracheotomy. 


728  DIPHTHERIA 

In  this  troublesome  class  of  cases  we  are,  however,  reluctant  to 
recommend  tracheotomy  except  as  a  dernier  ressort.  This  is  because 
of  the  difficulty  we  have  many  times  experienced  in  getting  rid  of  a 
retained  tracheal  cannula.  One  such  patient  is  at  the  date  of  writing 
in  the  hospital^  having  worn  the  cannula  for  about  two  months. 

After  returning  to  their  homes,  three  of  our  patients  of  this  description 
were  taken  to  a  general  hospital  in  this  city  and  placed  under  the  care 
of  a  surgeon.  An  operation  was  performed  with  the  view  of  overcoming 
the  stenosis  due  to  contraction  of  the  cicatricial  tissue  in  the  larynx, 
but  in  each  instance  the  operation  was  unsuccessful,  and  the  tracheal 
cannula  had  to  be  continued.  Two  of  these  unfortunate  children  subse- 
quently contracted  pneumonia  and  died.  There  are  three  other  ex- 
patients  of  whom  we  have  knowledge  with  retained  tracheal  tubes; 
in  one  the  retention,  at  the  time  of  writing,  has  extended  over  a  period 
of  six  months,  and  in  the  other  two  of  about  four  years  each. 

The  difficulty  in  getting  rid  of  the  tracheal  cannula  in  this  class  of 
cases  may  not  be  due  alone  to  cicatricial  tissue  in  the  larynx  caused  by 
the  intubation  tube.  In  addition  to  this  a  later  obstruction  is  not 
infrequently  developed  as  the  direct  result  of  the  inflammation  caused 
by  the  long-retained  cannula.  This  occurs  at  the  upper  angle  of  the 
wound  and  may  be  in  the  nature  of  a  stricture,  or  the  larynx  may  be 
completely  occluded  by  cicatricial  tissue.  This  condition  is  even  of 
more  serious  import  than  the  former.  We  have  seen  two  such  cases  in 
which  it  was  impossible  to  pass  a  probe  through  the  lumen  of  the  larynx, 
either  by  way  of  the  mouth  or  the  tracheal  wound;  and  the  voice,  even  in 
the  faintest  whisper,  was  lost,  which  proved  that  no  air  passed  through 
the  larynx.  According  to  O'Dwyer,  a  stricture  of  this  description 
develops  in  a  large  proportion  of  young  subjects  when  the  operation 
is  high,  involving  the  cricoid  cartilage  or  its  immediate  vicinity.  He 
says:  "When  the  wound  is  still  higher,  that  is,  wholly  within  the  larynx, 
complete  occlusion  with  adhesion  of  the  vocal  cords  is  very  liable  to 
occur,"  etc. 

As  to  the  treatment  of  chronic  stenosis  of  the  larynx,  we  believe  that 
long-continued  intubation  offers  the  best  results.  As  soon  as  the  tube 
is  once  introduced,  no  matter  how  small  it  may  be,  the  chief  difficulty 
is  overcome.  After  this,  tubes  of  graduated  sizes  should  be  employed, 
one  after  the  other,  until  the  one  suited  to  the  age  of  the  child  is  reached. 
As  already  stated,  the  tube  may  have  to  be  worn  intermittingly  for  a 
very  long  time  before  the  cicatricial  tissue  loses  its  power  to  contract. 
The  physician  should  not  become  discouraged  too  soon,  but  persevere, 
as  it  may  sometimes  require  years  to  remedy  the  difficulty. 

^Vhen  occlusion  of  the  larynx  is  complete,  or  nearly  so,  whether 
caused  by  the  intubation  tube  or  a  long-retained  tracheal  cannula,  it 
will  be  found  impossible  to  introduce  a  croup  tube  of  the  smallest  size. 
Such  cases  are  difficult  of  management  by  the  general  practitioner 
and  had  better  be  referred  to  the  laryngologist.  We  believe,  however, 
that  instead  of  attempting  to  force  an  entrance  from  above  downward, 
it  is  better  to  etherize  the  patient  and  enlarge  the  tracheal  wound  at 


rilK  TREATMENT  OF  J)I  I'llTII  Kill  A  729 

its  upper  angle  so  as  to  admit  of  tlic  introduction  of  a  soniul  from  hfilow. 
In  this  way  the  sound  is  h'ss  Hable  to  injure  the  parts  by  catching  in 
the  ventricles.  The  intubation  tube  should  then  be  introduced  and 
worn  continuously  for  one  or  two  weeks,  after  which  it  should  be 
employed  intermittingly  until  a  cure  is  eff('ct(;d.  This  procedure  was 
recommended  by  0'J)wyer  in  a  ])af)er  read  l)('for(!  the;  British  Medical 
Association  in  1804,  on  "Treatment  of  Chronic  Stenosis  of  the  Larynx 
by  Intubation."  In  this  paper  O'Dwyer  says:  "The  length  of  time 
that  intermittent  intubation  will  be  required  to  effect  a  permanent  cure 
will  be  influenced  largely  by  the  amount  of  cicatricial  tissue  present, 
and  its  location.  If  confined  to  the  chink  a  more  S})C(;dy  result  may 
be  expected,  because  of  the  stretching  which  is  exerted  by  the  expansion 
of  the  glottis  with  every  breath.  After  the  normal  lumen  of  the  larynx 
has  been  restored,  or  at  least  ample  breathing  room  secured,  a  tube 
should  be  inserted  once  or  twice  a  week,  and  allowed  to  remain  in 
position  from  twelve  to  twenty-four  hours.  This  interval  can  Ije  gradu- 
ally increased  according  to  indications,  and  continued  imtil  the  tendency 
to  recontraction  has  been  permanently  overcome." 

After  the  introduction  of  the  intubation  tube  in  these  cases  of  chronic 
stenosis  in  which  tracheotomy  has  been  performed,  it  is  desirable  that 
the  tracheal  wound  should  be  kept  open  for  some  time.  If  it  could  be 
kept  patulous — a  thing  difhcult  to  accomplish  in  a  child — the  liability 
of  the  tube  being  coughed  out  would  be  greatly  lessened.  A  special 
tube  or  combination  of  tubes  that  would  meet  this  indication  seems 
to  be  an  important  desideratum.  At  any  rate,  O'Dwyer's  advice  should 
be  heeded.  It  is  as  follows:  "In  practising  intubation  for  the  removal 
of  a  tracheal  cannula,  the  wound  under  all  circumstances  must  be  kept 
open  until  sufficient  breathing  room  through  the  natural  passage  has 
been  secured  to  sustain  life,  in  case  the  tube  should  be  coughed  out. 
This  is,  as  a  rule,  extremely  difficult  to  accomplish,  especially  in  cliildren. 
The  hard-rubber  plug  devised  by  Drs.  Pitts  and  Brook,  and  used  in  a 
series  of  cases,  appears  to  be  most  practicable  for  this  purpose.  It  is 
provided  with  a  collar  similar  to  that  on  a  tracheal  cannula,  by  which 
it  can  be  held  in  position." 

Shurly,^  of  Detroit,  believes  that  the  cure  in  cases  of  prolonged  intu- 
bation may  be  hastened  by  smearing  the  tube  with  an  ointment  com- 
posed of  alum  and  vaselin.  Louis  Fischer,  of  New  York,  likewise 
recommends  10  per  cent,  alum  or  ichthyol-gelatin. 

1  A  paper  read  in  the  Section  on  Diseases  of  Children,  American  Medical  Association,  1903,  on 
"  Prolonged  Intubation  Tubes,  with  a  Method  Leading  to  their  Extraction." 


CHAPTEKXIY. 

DIPHTHERIA  {Continued). 
THE  SERUM  TREATMENT  OF  DIPHTHERIA. 

The  antitoxin  method  of  treating  infectious  diseases  may  be  said 
to  have  had  its  origin  in  the  scientific  investigations  of  Pasteur  in  1880. 
He  then  made  the  discovery  that  an  unusually  mild  attack  of  fowl 
cholera  may  be  produced  in  chickens  by  inoculating  them  with  an 
attenuated  or  non-virulent  virus  of  that  disease.  Chickens  thus  inocu- 
lated, he  found,  were  thereby  rendered  immune  to  this  affection.  He 
also  applied  this  discovery  to  anthrax  in  sheep  with  similar  results. 
Later — in  1886 — Salmon  and  Smith  showed  the  great  practical  value 
of  Pasteur's  discovery  by  an  application  of  this  principle  to  the  protec- 
tion of  swine  against  hog  cholera. 

With  a  knowledge  of  the  fact  that  the  rat  and  the  frog  were  peculiarly 
refractory  to  the  operations  of  the  anthrax  bacilli,  Behring  showed  by 
experiment  that  the  blood  taken  from  these  animals  was,  within  cer- 
tain limits,  efficacious  against  the  production  of  anthrax  in  other 
animals. 

In  1890  Behring  and  Kitasato  startled  the  medical  world  with  the 
announcement  that  if  an  animal  be  immunized  against  tetanus  or 
diphtheria  the  serum  of  the  blood  of  that  animal,  when  injected  in 
sufficient  quantity,  is  capable  not  only  of  immunizing  other  animals 
against  an  attack,  but  also  of  effecting  a  cure  when  attacked.  These 
observers  published  their  discovery  in  the  follovdng  language:  "Our 
researches  on  diphtheria  (Behring)  and  on  tetanus  (Kitasato)  have  led 
us  to  the  question  of  immunity  and  cure  of  these  two  diseases,  and  we 
have  succeeded  in  curing  infected  animals  and  in  immunizing  healthy 
animals,  so  that  they  have  become  incapable  of  contracting  diphtheria 
or  tetanus."^ 

In  this  connection  it  is  due  Aronson  to  state  that,  with  equal  diligence 
in  this  field  of  labor,  he  also  succeeded  soon  afterward  in  immunizing 
animals  against  diphtheria. 

After  the  investigations  of  these  men,  it  is  only  fair  to  mention  the 
confirmatory  experiments  of  Fraenkel,  Wernicke,  Roux,  and  others, 
who  likewise  succeeded  in  producing  in  animals  an  immunity  against 
diphtheria  by  inoculating  them  with  virulent  or  somewhat  attenuated 
cultures  or  with  diphtheria  toxin.  But,  as  already  shown,  Behring 
carried  these  researches  one  step  farther  by  demonstrating  that  the 
blood  of  immune  animals  contained  a  substance  which  antagonizes 

'  Quoted  by  Lennox  Browne,  Diphtheria  and  its  Associates. 


THFj  Sr<]RJIM  TRMATMMNT  OF  DH'II'I'II FltlA  7.';] 

tho  (liphtlicria,  toxin.  Tlicsc  iinporlaiii  studies  fDiisfiliitc  tlic  foiiriflufion 
upon  which  has  been  based  the  mocJern  antitoxin  treatirif-nf  of  rjiph- 
theria. 

The  last  link  in  the  chain  of  these  interestinff  investigations  having 
been  forj^ed,  it  now  remained  to  apply  the  dis(;overies  tiiat  liad  been 
made  to  their  special  purpose  of  ciwin^  (Hj)htlieria  in  human  beings. 
Here,  as  in  the  entire  field  of  this  research,  the  work  of  Behring  was 
most  productive.  Tie  succeeded  in  reaching  the  goal  of  his  investigations, 
and,  together  with  Kossel,  in  1898,  recorded  30  cases  of  fiif)htheria 
in  human  subjects  which  had  been  benefited  l)y  the  use  of  serum 
from  the  blood  of  animals  artificially  immunized. 

In  1894,  Ehrlich,  Kossel,  and  Wassermann  reported  223  cases  treated 
with  antitoxic  serum,  with  a  mortality  rate  of  23  per  cent. 

In  June,  1894,  Katz,  a  colaborer  of  Baginsky,  reported  to  the 
Berlin  Medical  Society  128  cases  of  diphtheria  which  had  been  treated 
with  serum  produced  from  one  of  Aronson's  horses.  This  number  was 
subsequently  increased  by  Baginsky  to  163  cases,  with  the  surprisingly 
low  death  rate  of  12.9  per  cent. 

While  the  announcements  of  the  foregoing  results  were  received 
with  intense  interest,  the  culminating  point  of  enthusiasm  was  reached 
at  the  Eighth  International  Congress  of  Hygiene  and  Demography, 
held  at  Budapest  in  September,  1894,  when  Roux  presented  his  brilliant 
paper  on  the  subject  of  the  serum  treatment  of  diphtheria  (I>ennox 
Browne).  He  announced  that  he  had  confirmed,  by  experiments  in  the 
Pasteur  Institute,  all  the  important  statements  made  by  Behring  and 
others  who  labored  contemporaneously,  and  presented  the  records  of  a 
large  number  of  cases  in  which  the  serum  treatment  had  been  employed 
successfully  in  the  human  subject,  "and,"  as  Lennox  Browne  so  aptly 
says,  "by  comparative  statistics,  enforced  the  attention  of  the  whole 
medical  world  to  a  consideration  of  its  claims." 

Theory  of  the  Action  of  Antitoxin. — There  seems  to  be  very  Uttle 
known  as  to  the  modus  operandi  of  antitoxin  in  the  treatment  of  diph- 
theria. It  exerts  no  bactericidal  effect  upon  the  Klebs-I.oeffler  bacilli, 
although  it  is  supposed  to  arrest  the  inflammatory  process  caused 
by  these  organisms.  It  is  also  believed  that  it  does  not  act  chemically 
or  otherwise  upon  the  toxin  circulating  in  the  blood,  but  rather  upon 
the  living  cells  of  the  body,  through  whose  agency  the  cure  is  effected. 
Park  says:  "After  the  cells  have  been  to  a  certain  extent  affected  by 
the  toxin,  the  protective  power  of  the  antitoxin  can  no  longer  be  exerted 
and  the  lesions  progress  in  spite  of  it." 

While  the  mode  of  action  of  the  antitoxic  serum  cannot  be  satisfac- 
torily explained,  yet  there  is  no  doubt  that  it  is  capable  of  neutrahzing 
the  effect  of  the  toxin  of  diphtheria  in  animals.  This  has  been  demon- 
strated thousands  of  times  in  the  laboratory  by  bacteriologists.  Park 
says:  "We  have  every  reason  to  expect  that,  since  the  toxin  in  human 
diphtheria  is,  so  far  as  we  can  determine,  exactly  the  same  toxin  as  that 
in  diphtheria  in  animals,  tliis  power  of  the  antitoxin  to  make  harmless 
the  toxin  will  manifest  itself  in  man  under  similar  conditions." 


732  DIPHTHERIA 

Preparation  of  Antitoxin. — As  already  pointed  out,  to  render  an 
animal  immune  to  the  diphtherial  poison  it  is  held  to  be  sufficient  to 
gradually  accustom  that  animal  to  the  action  of  the  poison.  The 
serum  of  an  animal  thus  treated  is  believed  to  possess  not  only  prophy- 
lactic but  also  .curative  qualities.  The  goat  has  been  used  in  this  way 
for  the  production  of  antitoxin;  but  in  order  to  obtain  a  more  abundant 
yield — as  well  as  for  some  other  reasons — the  horse  is  the  animal  now 
generally  preferred. 

Having  eliminated  the  possibility  of  the  existence  of  glanders  and 
tuberculosis  by  the  proper  tests,  the  horse  is  brought  into  a  good  con- 
dition by  rest,  diligent  grooming,  and  careful  feeding,  preparatory  to 
beginning  the  process  of  immunization.  According  to  Park,  the  follow- 
ing method  is  employed  in  the  production  of  antitoxic  serum  by  the 
Health  Department  of  New  York  City: 

To  prepare  a  strong  diphtheria  toxin  a  virulent  culture  of  the  Klebs- 
Loeffler  bacillus,  grown  under  special  conditions,  is,  at  the  end  of  a 
week's  growth,  rendered  sterile  by  the  addition  of  10  per  cent,  of  a 
5  per  cent,  solution  of  carbolic  acid.  In  twenty-four  hours  it  is  filtered 
through  sterile  filter  paper  and  stored  in  bottles  in  a  cool  place.  A 
number  of  horses  are  injected  with  an  amount  of  toxin  sufficient  to 
kill  ten  thousand  guinea-pigs  of  250  grams  weight  each  (about  44  c.c. 
of  strong  toxin).  With  each  injection  of  toxin  10,000  units  of  antitoxin 
are  given.  After  from  three  to  five  days,  when  the  fever  has  subsided, 
a  second  injection  of  a  slightly  larger  dose  is  given.  Increasing  doses 
of  toxin  are  then  given  at  intervals  of  five  to  ten  days,  until,  at  the  end 
of  two  months,  from  ten  to  twenty  times  the  original  amount  is  given. 
The  horses  are  then  bled  and  the  blood  serum  tested  for  antitoxin. 
Those  animals  yielding  less  than  200  units  in  each  cubic  centimetre 
are  discarded. 

The  remaining  horses  are  then  further  treated  with  ascending  doses 
of  toxin.  At  the  end  of  three  months  the  serum  should  contain  from 
300  to  800  units  of  antitoxin  to  each  cubic  centimetre.  The  best  horses 
will  furnish  high-grade  antitoxin  for  years.  A  three  months'  freedom 
from  toxin  injection  should  be  given  the  horses  each  year. 

The  blood  is  obtained  by  plunging  a  sharp-pointed  cannula  into  the 
jugular  vein.  It  is  received  in  Ehrlenmeyer  flasks  and  allowed  to  clot, 
the  serum  then  being  siphoned  off. 

Antitoxin  is  a  proteid  substance  of  unknown  chemical  composition. 
It  is  destroyed  by  heat  55°  C,  and  is  precipitated  from  its  solution  in 
the- same  manner  as  globulins. 

As  already  pointed  out,  antitoxin  possesses  the  property  of  neutral- 
izing, within  certain  limitations,  the  diphtheria  toxin  within  the  body. 
That  is  to  say,  when  a  given  amount  of  antitoxin  is  injected  into  an 
animal  with  or  just  before  a  certain  quantity  of  the  toxin,  it  abrogates 
the  poisonous  effect  of  the  latter. 

Behring  and  Ehrlich  applied  the  term  "antitoxin  unit"  to  an  amount 
of  antitoxin  capable  of  protecting  the  life  of  a  guinea-pig  weighing 
250  grams   from    one  hundred    fatal    doses  of  toxin.      Ehrlich   later 


Till':  HI': HUM  Tia<:ATMi:NT  oi''  Dii'iiriiHiaA  733 

pointed  out  the  variability  of  ihv.  (Ilplithcria  toxin,  and  tlicreFore  tli(! 
liability  of  error  in  such  standardization.  Park,  who  experimented 
with  toxins  of  did'erent  potencies,  gives  the  following  definition  of  an 
antitoxin  unit:  "The  amount  of  antitoxin  necessary  to  f)roteet  the 
hfe  of  a  guinea-pig  from  one  himdred  fatal  doses  of  a  toxin  similar 
to  that  adopted  as  a  standard,  namely,  one  liaving  th(!  cliaraeteristics 
of  toxins  in  cultures  at  the  height  of  their  toxicity."  lie  .says:  "This 
amount  of  poison  is  produced  by  the  growth  for  one  week  of  a  virulent 
baciHus  in  1  c.c.  of  bouillon." 

The  Serum. — The  serum  varies  considerably  in  color,  though  it 
should  be  clear  and  free  from  anything  that  looks  lik(!  bacterial  growth. 
It  is  maintained  in  an  aseptic  state  by  putting  it  into  sterilized  bottles, 
which  are  hermetically  sealed  and  kept  in  a  cool  place.  It  is  fpiite 
common  to  use  some  preservative,  such  as  camp»hor,  carbolic  acid, 
trikresol,  and  the  like. 

The  serum  on  the  market  varies  greatly  in  antitoxin  units.  It  is 
believed  that  each  cubic  centimetre  should  contain  at  least  100  anti- 
toxin units,  but  it  is  desirable  to  have  it  much  stronger.  Originally, 
Behring's  firm  put  up  three  strengths  in  vials  of  about  10  c.c.  each,  as 
follows : 

No.  1,  containing  600  units,  which  was  regarded  as  a  suitable  dose 
for  a  child  at  the  onset  of  an  ordinary  attack  of  diphtheria. 

No.  2,  containing  1000  units,  for  a  severe  attack  in  children. 

No.  3,  containing  1500  units,  for  adults,  or  a  very  severe  form  of 
the  disease  in  children. 

The  serum  prepared  in  this  country  is  put  up  in  vials  containing 
from  5  c.c.  to  10  c.c,  and  represents  a  strength  of  100  to  500  antitoxin 
units  to  each  cubic  centimetre.  The  number  of  units  in  each  vial 
should  appear  on  the  label. 

Dosage. — In  considering  the  dose  one  should  think  of  antitoxin 
units  rather  than  the  quantity  of  the  serum;  but  it  must  be  admitted 
that  there  is  no  fixed  dose.  In  the  present  state  of  our  knowledge  it 
is  impossible  to  fix  the  dose  on  the  basis  of  age,  as  in  the  case  of  drugs. 
Perhaps  most  practitioners  inject  as  many  antitoxin  units  into  a  child 
as  into  an  adult.  This  does  not  seem  unreasonable  when  we  consider 
that  the  amount  of  toxin  absorbed,  and  which  we  seek  to  neutralize 
or  counteract,  is  in  all  probability  as  great  in  the  former  as  in  the  latter. 
It  is  also  not  improbable  that  the  younger  the  child  the  greater  the 
susceptibility  to  the  toxin  of  the  disease,  with  a  less  power  of  resistance, 
and  "consequently,"  as  Lennox  Browne  remarks,  "if,  as  has  been 
suggested,  the  remedy  acts  by  cell  stimulation,  the  greater  the  necessity 
for  a  large  dose  of  the  serum;  or,  in  other  words,  since  the  young  cell 
elements  are  so  extremely  sensitive  to  the  diphtherial  poison,  they 
require  to  be  fortified  all  the  more  strongly  in  order  to  exercise  an 
effective  resistance."  We  may  state,  on  the  authority  of  the  writer 
just  quoted,  that  Roux,  in  his  first  announcement,  speaking  of  the 
serum  prepared  at  the  Pasteur  Institute,  advised  that  20  c.c.  (repre- 
senting, probably,  2000  units)  be  given  to  every  patient — adult,  or  child 


734  DIPHTHERIA 

above  one  year — so  soon  as  seen,  and  even  in  advance  of  the  bacterio- 
logical diagnosis,  stating  that  for  children  under  one  year  the  first  dose 
should  be  as  many  cubic  centimetres  as  the  child  is  months  old.  In  very 
severe  cases,  he  said,  the  dose  should  be  as  much  as  30  c.c,  or  even  more. 

It  has  been  deemed  advisable  by  the  most  competent  observers  to 
regulate  the  dose  according  to  the  time  that  has  elapsed  since  the  onset 
of  the  disease  and  the  severity  of  the  attack.  As  we  have  just  shown, 
Behring  believed  that  a  dose  of  600  units  was  sufficient  for  a  child  at 
the  onset  of  an  ordinary  attack,  but  if  the  case  be  a  ery  severe,  or  far 
advanced  when  first  seen,  the  dose  should  be  increased  to  1500  units. 

We  feel  that  what  Park^  has  said  on  the  subject  of  dosage  is  worth 
quoting.  He  writes:  "The  size  of  the  dose  should  be  measured  chiefly 
by  the  extent  and  intensity  of  the  disorder;  also,  but  to  a  less  degree, 
by  the  size  of  the  patient  and  the  duration  of  the  illness.  For  young 
children,  with  but  moderate  lesions  of  the  tonsils  or  palate,  a  single 
dose  of  1000  to  1500  units  will  suffice.  For  older  children  and  adults 
1000  to  2000  units  should  be  given.  In  children  who  are  already 
seriously  ill  or  who  already  show  the  toxic  effects,  or  in  whom  the 
larynx  is  involved,  a  dose  of  1500  to  3000  units    ...    is  necessary. 

"If  the  symptoms  do  not  abate,  another  1000  to  2000  units  may 
be  given  on  the  following  day.  In  a  few  cases  still  a  third  injection  is 
required.  Exceptionally,  a  week  or  ten  days  after  administering  the 
antitoxin,  a  slight  return  of  exudate  may  appear;  here  another  moderate 
injection  is  indicated.  Where  these  doses  have  not  benefited  it  is 
doubtful  if  larger  ones  will  succeed. 

"At  the  New  York  Hospital  for  Contagious  Diseases  for  several 
months  one-half  of  the  severe  cases  received  on  admission  3000  units, 
and  again  on  the  following  day  3000  more.  If  no  improvement  followed, 
a  third  3000  units  were  given.  The  other  half  received  2000  units  on 
admission,  and  a  second  2000  in  eighteen  hours.  So  far  as  one  could 
judge,  those  receiving  the  lesser  amount  did  as  well  as  those  receiving 
the  very  large  amounts.  On  the  other  hand,  no  additional  disagreeable 
effects  were  noticed  from  the  larger  quantities."^ 

McCollom,^  of  the  South  Department  Hospital,  Boston,  recommends 
that  antitoxin  be  administered  in  large  doses.  He  advises  that  4000 
units  be  given  at  once,  and  that  this  dose  be  repeated  at  intervals  of 

1  Loomis-Thompson,  American  System  of  Practical  Medicine. 

-  While  these  pages  are  going  through  the  press  we  note  in  the  Archives  of  Pediatrics,  December, 
1904,  an  abstract  of  a  discussion  in  the  New  York  Academy  of  Medicine  on  the  dosage  of  diphtheria 
antitoxin  In  which  Dr.  Park's  views  are  given  as  follows  :  He  said  that  for  three  years  he  had  experi- 
mented with  antitoxin  in  doses  greatly  varying  in  size  :  during  one  year  the  dose  was  10,000  to  20,000 
units;  the  next  year  it  was  between  5000  and  10,000  units;  the  third  year  it  was  between  3000  and 
5000  units.    Hfe  said  it  was  very  difQcult  to  find  out  which  dosage  produced  the  best  results. 

In  bad  cases  of  diphtheria  Dr.  Park  advocated  using  large  doses.  In  mild  cases,  either  early  or 
late,  involving  tonsils  and  pharynx,  he  used  2000  units ;  in  severe  early  cases  4000  units  ;  in  ordi- 
nary laryngeal  cases  5000  units;  in  malignant  cases,  tonsillar,  pharyngeal,  or  nasal,  10,000  units,  and 
repeating  this  dose  at  the  end  of  twelve  hours  unless  the  patient  is  distinctly  better.  He  emphasized 
the  fact  that  the  antitoxin  should  be  given  for  the  diphtheria  and  not  for  any  accompanying  condi- 
tion like  pneumonia. 

3  A  Plea  for  Larger  Doses  of  Antitoxin,  Medical  and  Surgical  Reports  of  the  Boston  City  Hospital, 
1900,  eleventh  series. 


77//';  sf<:ni/M  tiii<atmi<:nt  of  I)II'Iitiii-:i{i.\  7.35 

twelve  hours,  presumably  until  improvement  takes  place.  He  says 
that  since  larger  closes  hav(;  been  givcm  the  death  rate  among  his  cases 
of  diphtheria  has  been  inat(;rially  rcchiced,  the  rcfhiction  being  especially 
noticeable  among  the  appar(;ntly  moribund  cases.  The  most  satisfactory 
results  were  obtained  when  the  serum  treatment  was  begun  at  an 
early  stage  of  the  disease. 

The  dose  employed  by  us  in  the  Municipal  Hospital,  Philadelphia, 
has  varied  greatly.  In  our  early  experienc(;  with  tiie  lemedy  we  followed 
the  recommendations  of  Behring  as  to  dosage.  Finding,  however,  that 
the  results  were  not  as  satisfactory  as  we  were  led  to  believe  they  should 
be,  the  dose  was  increased.  For  a  few  years  we  gave  1000  to  2000  units 
at  a  dose,  which  was  repeated  in  severe  cases  at  intervals  of  twelve 
hours,  until  two,  three,  or  more  doses  were  given.  Later,  the  dose  was 
considerably  increased.  For  some  months  in  succession,  on  one  or  two 
occasions,  each  patient  admitted  to  the  hospital  received  from  6000 
to  9000  units,  and  this  dose  was  repeated  two  or  three  times  in  many 
instances.  We  have  more  than  once  administered  to  a  child  20,000 
units  at  a  single  injection.  Very  many  of  our  patients  have  received 
as  much  as  20,000  units,  and  even  more,  in  divided  doses.  The  largest 
total  quantity  which  we  have  administered  was  47,000  units  to  an 
adult  female.  This  was  given,  of  course,  in  divided  doses.  We  are 
able  to  bear  testimony  with  others  to  the  fact  that  large  doses  of  anti- 
toxin do  not  appear  to  be  harmful.  Our  experience  is,  furthermore, 
in  accordance  with  Park's,  in  that  we  have  found  that  the  patients 
who  received  the  medium-sized  doses  did  as  well  as  those  receiving  the 
extraordinarily  large  doses. 

It  appears  preferable  that  the  first  dose  should  be  a  fairly  large 
one — at  least  from  2000  to  4000  units.  In  very  severe  cases  doses  of 
3000  units  each  should  be  repeated  at  intervals  of  twelve  hours  until 
6000  to  12,000  units  have  been  given.  It  is  doubtful  whether  larger 
doses  will  afford  any  additional  benefit. 

All  observers  agree  that  antitoxin  is  most  efficacious  when  administered 
promptly  at  the  beginning  of  an  attack  of  diphtheria.  Some  believe 
that  it  is  useless  after  the  third  day  of  the  disease.  But  if  it  should 
happen  in  any  case  that  the  disease  is  not  recognized  until  a  later  stage, 
it  is  advisable  to  administer  the  remedy,  and  thus  give  the  patient  the 
benefit  of  the  doubt. 

It  is  our  practice  to  administer  antitoxin  to  all  patients  who  are  sent 
to  the  hospital  with  the  diagnosis  of  diphtheria.  Tliis  is  a  rule  which 
is  carried  out  irrespective  of  the  stage  of  the  disease  or  the  result  of 
the  bacteriological  examination.  Immediately  after  admission  a  bath 
is  given,  and  this  is  followed  by  a  large  dose  of  antitoxin,  which  is 
repeated  in  twelve  to  eighteen  hours  in  the  severer  cases.  The  number 
of  repetitions  may  depend  upon  the  disposition  of  the  membrane  to 
separate  and  peel  off. 

The  Effect  of  Antitoxin  upon  the  Local  Process. — According  to  Roux 
and  most  other  writers  the  effect  of  antitoxin  upon  the  pseudomembrane 
of  diphtheria  is  very  prompt  and  positive.    INIany  observers  have  found 


736  DIPHTHERIA 

that  the  membrane  ceased  to  spread  in  twenty-four  hours  after  the 
dose  was  given,  commenced  to  separate  twenty-four  hours  later,  and 
entirely  disappeared  in  the  course  of  four  or  five  days,  leaving  the 
mucous  membrane  of  the  fauces  quite  normal.  It  has  been  frequently 
noted  that  the  false  membrane  early  undergoes  a  whitening  process, 
with  fissuring  of  its  surface,  causing  it  to  resemble,  in  the  imagination 
of  some  writers,  "chicken  fat."  It  is  believed  that  the  underlying 
tissue  is  less  liable  to  be  destroyed  by  ulcerative  action,  and  that  the 
membrane  may  often  be  detached  and  removed  with  but  little  or  no 
hemorrhage.  Recurrence  of  the  membrane  is  believed  to  be  less  frequent 
than  under  the  old  treatment. 

Antitoxin,  according  to  some  observers,  also  exerts  a  favorable 
influence  upon  the  constitutional  symptoms.  It  is  often  mentioned  in 
clinical  reports  that  the  temperature  begins  to  fall  and  general  improve- 
ment takes  place  as  soon  as  the  serum  is  injected.  We  have  called 
attention  to  the  fact  that  the  temperature  in  diphtheria  is  not  high, 
except  at  the  onset  of  the  disease.  It  usually  falls  to  normal,  or  nearly 
so,  on  the  third  or  fourth  day  of  the  illness.  A  persistently  high  temper- 
ature would  indicate  the  presence  of  some  complication. 

Mode  of  Administering  Antitoxin. — Any  syringe  capable  of  being 
sterilized,  and  large  enough  to  hold  5  to  10  c.c,  may  be  used  to  inject 
the  serum.  It  matters  but  little  where  it  is  injected.  Some  prefer  one 
place,  and  others  another.  We  usually  select  the  lower  abdominal 
region,  for  the  reason  that  any  local  tenderness  following  the  injection 
is  not  aggravated  by  the  pressure  of  clothing,  or  by  the  patient's  recum- 
bent position.  The  syringe  having  been  sterilized  by  means  of  boiling 
water,  the  skin  at  the  site  selected  should  be  thoroughly  scrubbed  with 
soap  and  water  and  then  washed  with  alcohol.  After  filling  the  syringe 
with  the  antitoxin  it  should  be  held  with  the  point  upward  and  the 
piston  pushed  in  slightly  so  as  to  exclude  the  bubbles  of  air.  The  skin 
is  then  pinched  up  by  the  thumb  and  forefinger  of  one  hand,  the  needle 
introduced,  and  the  serum  injected  slowly.  After  withdrawing  the 
needle  a  pad  of  cotton-wool  may  be  placed  over  the  site  of  puncture, 
and  this  with  the  exuding  drop  of  serum  seals  the  wound  similar  to 
collodion.  The  material  is  readily  absorbed.  For  about  twenty-four 
hours  after  the  injection  has  been  given,  there  is  usually  a  localized 
redness,  with  slight  oedema,  and  moderate  pain  on  pressure.  Abscesses 
sometimes  occur;  but  they  are  rare  when  the  technique  is  faultless. 

Limitations  of  Antitoxin. — It  is  not  claimed  for  diphtheria  antitoxin 
that  it  exerts  any  neutralizing  influence  over  the  poison  elaborated 
by  the  bacteria  commonly  associated  with  the  Klebs-Loeffler  bacilli. 
In  considering  the  symptomatology  of  diphtheria  we  called  attention 
to  the  fact  that  this  affection  is  not  infrequently  a  complex  disease, 
and  that  dangerous  symptoms  are  sometimes  produced  by  the  toxins 
of  the  associated  organisms.  It  is  evident  that  the  influence  of  anti- 
toxin in  such  cases  must  be  limited. 

Park  says :  "Another  limitation  is  suggested  by  the  results  of  experi- 
ments upon  animals.    It  is  known  that  after  the  infection  has  proceeded 


TlfK  SERT7M  TREATMENT  OF  hi I'llTII EUI A  737 

to  a  moderate  dej^ree  it  cannot  l)e  arrested  by  antitoxin.  Experience 
shows  that  in  human  beings  also  the  cells  no  long<'r  react  to  antitoxin 
after  a  certain  degree  of  poisoning  has  taken  place,  and  this  point  in 
some  eases  seems  to  occur  vcuy  early.  I  flouht  if  we  are  justified  in 
saying  that  in  these  the  actual  lesions  have  j)rogressed  so  far  that  without 
any  further  poisoning  life  has  l)(;com(;  im|)ossil)le.  I  believe  it  may 
be  possible  that  even  after  the  administration  of  antitoxin  the  poison 
goes  on  producing  further  lesions,  the  cells  already  affected  by  the 
toxin  not  responding  to  the  antitoxin.  There  are  exceptional  cases 
in  which  even  when  the  \intitoxin  is  given  early  it  apjiarently  fails  to 
fortify  the  cells  against  the  diphtheria  [)oison." 

The  Prophylactic  Power  of  Antitoxin.^ — It  has  been  shown  by  many 
observers  that  antitoxin  injected  subcutaneously  will  protect  an  indi- 
vidual against  an  attack  of  diphtheria.  Immunity  thus  conferred, 
however,  does  not  last  very  long — only  about  two  or  three  weeks. 
But  protection  may  be  continued  by  a  repetition  of  the  injection.  For 
immunizing  purposes  small  doses  have  been  found  to  be  sufficient 
(300  to  500  units,  according  to  the  age  and  size  of  the  person). 

Jacobi  cites  Slawyk's  report^  as  showing  the  prophylactic  power  of 
diphtheria  antitoxin.  It  appears  that  in  Heubner's  division  of  the 
Charity  Hospital  of  Berlin  relapses  of  endemic  outbreaks  were  quite 
common  in  spite  of  careful  preventive  measures  until  immunization 
by  antitoxin  was  resorted  to.  The  dose  administered  was  200  units, 
repeated  every  three  weeks.  In  this  way  the  place  remained  free  from 
the  disease.  As  a  matter  of  experiment  immunization  was  discontinued 
for  one  month,  when  three  cases  of  diphtheria  occurred,  one  of  which 
terminated  fatally.  The  preventive  injections  were  then  renewed,  and 
during  the  following  two  and  a  half  months,  up  to  the  time  the  report 
was  published,  no  new  case  had  occurred. 

Similar  results  have  been  observed  in  New  York  and  elsewhere. 
Park  has  shown  that  the  work  done  along  this  line  by  the  New  York 
Health  Department  has  been  very  successful.  Many  children  of  families 
in  which  diphtheria  occurred  were  protected  against  the  disease  by 
immunizing  doses  of  antitoxin.  Most  of  these  instances  were  among 
the  tenement-house  population.  The  cases  detailed  number  altogether 
1043.  He  says:  "In  a  large  percentage  of  the  whole  number  diph- 
theria bacilli  were  present  in  the  throat  when  the  serum  was  admin- 
istered, and  all  had  been  exposed  to  diphtheria  under  conditions  more 
or  less  favorable  for  the  transmission  of  the  disease.  Among  those 
immunized  3  cases  of  diphtheria  occurred  between  one  and  thirty  days 
after  the  treatment — i.  e.,  1  on  the  twelfth,  1  on  the  seventeenth,  and 
1  on  the  nineteenth  day,  respectively."  He  also  says  that  by  the  use 
of  this  agent  it  has  been  possible  to  stamp  out  diphtheria  in  four  large 
institutions  for  the  care  of  children  in  which  it  was  prevailing  in  more 
or  less  epidemic  form. 

Park^  has  summarized  the  1043  cases  as  follows: 

1  Deutsche  medicinische  Wochenschrift,  1898,  Xo.  6. 

2  Loomis-Thompson,  American  System  of  Practical  Medicine. 

47 


738 


DIPHTHERIA 


No.  of 

No.  of 

cases  of 
diphtheria 
developing 

No.  of 
cases 

No.  of 
cases  of 

No.  of  cases  of 

No.  of 

of  units 

devel- 

diphtheria 

diphtheria  that 

cases 

of  anti- 

among 
those  im- 
munized 
between 
one  and 
thirty  days. 

oping 

devel'ping 

occurred    In   the 

immu- 

toxin 

within 

after 

institution  previous 

nized. 

adminis- 

twenty- 

thirty 

to  immunization. 

tered. 

four 
hours. 

days. 

New  York  Infant  Asylum 

224 

100  to  200 

1  mild  on 

0 

6 

107  cases  in  108  days. 

(first  immunization). 

19th  day. 

New  York  Infant  Asylum 

245 

125  to  225 

1  mild  on 

0 

4 

6  cases  in  12  days. 

(second  immunization). 

12th  day. 

Nursery  and  Child's  Hos- 

136 

50  to  200 

0 

0 

0 

46  cases  in  90  days; 

pital. 

15  cases  in  15  days. 

New  York  Juvenile 

81 

150  to  250 

0 

0 

0 

12  cases ;  3  cases  in 

Asylum. 

2  days. 

New  York  Catholic  Pro- 

114 

150  to  600 

0 

1 

0 

5  cases  in  3  days. 

tectory. 

Bellevue  Hospital. 

11 

175  to  225 

0 

0 

0 

2  cases  in  10  days. 

Health  Department, 

232 

150  to  250 

1  mild  on 

(1:30 

1  or  more  cases  in 

Inspectors. 

19th  day. 

3 

3^  1  :  31 
(.1:55 

more  than  90 
families. 

Total, 

1043 

3 

4 

13 

Zuppinger/  in  reviewing  the  experience  of  others  in  various  countries 
on  the  preventive  serum  treatment  against  diphtheria,  presents  his 
own.  He  says  that  out  of  1000  children  exposed  to  this  malady  and 
treated  by  preventive  injections  of  antitoxin,  only  18  developed  the 
disease  later.  Of  this  number,  he  believes  that  11  had  already  con- 
tracted diphtheria,  as  the  symptoms  developed  at  once.  This  leaves 
only  7  cases  in  which  the  antitoxin  failed  to  protect. 

The  Commissioner  of  Health  of  Chicago  says  that  out  of  7051 
exposed  persons  who  received  each  an  immunizing  dose  of  antitoxin 
(500  units),  only  46  subsequently  developed  diphtheria,  but  all  recovered. 

In  the  Municipal  Hospital,  Philadelphia,  we  have  frequent  oppor- 
tunities of  noting  the  immunizing  power  of  antitoxin.  Each  year 
many  patients  are  sent  to  the  hospital  as  subjects  of  diphtheria  when 
the  disease  turns  out  to  be  something  else.  They  occupy  the  diphtheria 
wards,  and  consequently  are  freely  exposed  to  the  infection  of  that 
disease.  As  these  patients  are  supposed  to  be  suffering  from  diphtheria 
the  resident  physician  injects  the  antitoxin  as  soon  as  possible  after 
admission.  The  dose  administered  may  be  from  3000  to  6000  units. 
We  have  no  record  of  any  such  patient  falling  ill  with  diphtheria  while 
in  the  hospital.  For  the  last  three  years  we  are  able  to  report  193 
observations  of  this  kind. 

Evidence  of  the  Curative  Power  of  Antitoxin. — While  it  is  believed 
that  all  forms  of  diphtheria  are  liable  to  be  benefited  by  antitoxin, 
the  greatest  benefit  is  to  be  expected  and  doubtless  does  result  among 


1  Preventive  Antitoxin  Treatment,  Wiener  klinische  Wochenschrift,  Vienna. 


77//';  HI<:UUM  Tlil':ATMI<:NT  OF  DII'irrilhlHIA  7.'i(j 

the  uncomplicated  cases,  or  those  not  suffering  froin  a  rnixerl  infection. 
The  mortality  rates,  therefore,  will  Ik-.  foiiiKJ  to  vary,  acconlin^'ly  as 
the  complex  cases  are  in(;lu(ie(l  or  exelucjed  in  the;  eornpihition  r<f 
statistics. 

Since  the  advent  of  antitoxin,  diphtheria  statistics,  both  of  hospitals 
and  of  private  practice,  have  greatly  increased  and  are  constantly 
growing.  After  carefully  reviewing  this  large  amount  of  pul>lished 
data,  Biggs  and  Guerard  arrived  at  the  following  conclusions:'  "It 
matters  not  from  what  point  of  view  the  subject  is  regarded  if  the 
evidence  now  at  hand  is  properly  weighed,  but  one  conclusion  is  or 
can  be  reached — -whether  we  consider  the  percentages  of  mortality 
from  diphtheria  and  croup  in  cities  as  a  whole,  or  in  hospitals,  or  in 
private  practice;  or  whether  we  take  the  absolute  mortality  for  all  the 
cities  of  Germany  whose  population  is  over  15,000,  and  all  the  cities 
of  France  whose  population  is  over  20,000;  or  the  absolute  mortality 
for  New  York  City,  or  for  the  great  hospitals  in  France,  Germany, 
and  Austria;  or  whether  we  consider  only  the  most  fatal  cases  of  diph- 
theria, the  laryngeal  and  operative  cases;  or  whether  we  study  the 
question  with  relation  to  the  day  of  the  disease  on  which  treatment 
is  commenced,  or  the  age  of  the  patient  treated;  it  matters  not  how^ 
the  subject  is  regarded  or  how  it  is  turned  for  the  purpose  of  comparison 
with  previous  results,  the  conclusion  reached  is  always  the  same,  namely, 
there  has  been  an  average  reduction  of  mortality  from  the  use  of  anti- 
toxin in  the  treatment  of  diphtheria  of  not  less  than  50  per  cent.,  and 
under  most  favorable  conditions  a  reduction  to  one-quarter,  or  even 
less,  of  the  previous  death  rate.  This  has  occurred  not  in  one  city  at 
one  particular  time,  but  in  many  cities,  in  different  countries,  at  different 
seasons  of  the  year,  and  always  in  conjunction  with  the  introduction 
of  antitoxin  serum  and  proportionate  to  the  extent  of  its  use." 

Among  the  earlier  effects  of  antitoxin  is  the  whitening  process  which 
the  false  membrane  undergoes.  Following  tliis,  the  membrane  begins 
to  separate,  and,  according  to  Roux  and  many  other  observers,  entirely 
disappears  in  four  or  five  days  after  the  injection  of  the  serum. 

The  subjoined  table  shows  the  day  of  the  disease  w^hen  antitoxin 
was  administered  to  350  patients  in  the  Municipal  Hospital,  Phil- 
adelphia, and  the  day  on  which  the  throat  was  declared  free  of  mem- 
brane.   These  were  not  selected  cases,  but  taken  at  random. 

1  Quoted  by  Park,  Twentieth  Century  Practice  of  Medicine. 


740 


DIPHTHERIA 


The  Day  of  the  Disease  on  which  the  Throat  was  Declared 
Free  of  Membrane. 


Day  of  disease 
on  which  anti- 
toxin was 
administered. 

No. 

of 

cases. 

i 

•6 

(N 

CO  iTJi 

si 

.£3 

00 

OS 

0 

g 

.0 

CO 

S 

J3 

^' 

01 

o3 

First .    . 
Second  . 
Third    . 
Fourth  . 
Fifth 

25 
118 
91 
53 
26 
12 

8 
12 

4 

1 

1 

2 

3 

8 

6 
17 
6 

■5 

19 
16 
1 

3 

18 

16 

7 

2 

2 
12 
15 

8 
8 

2 
10 
10 

7 
3 
2 

1 

10 
9 

10 
6 
3 

4 

1 
12 

7 
5 
2 
1 

4 
2 

1 

4 
2 
3 

1 

1 
2 

1 

2 
2 
3 
1 
1 

1 

1 
1 

2 

1 
1 

1 

1 

3 
3 

1 

1 

4 

1 

1 
1 

1 

2 

1 

2 

1 

1 

On  the  28d,  one. 

Sixth 

On  the  30th,  one. 

Seventh 
Eighth  . 
Ninth    . 

On  the  27th,  one. 

1 

2 

Tenth    . 

! 

I 

Total 

350 

1 

2 

11 

29' 41  46 

1 

45 

35 

42 

35 

15 

10 

8 

7 

6 

1 

5 

3 

3 

1 

It  may  be  seen  in  the  above  table  that  the  earher  in  the  disease  the 
antitoxin  was  administered,  the  sooner  the  membrane  disappeared. 

Lennox  Browne,  however,  beheves  that  antitoxin  is  not  a  very  im- 
portant factor  in  hastening  the  separation  or  disappearance  of  the  mem- 
brane. He  shows  comparisons  between  92  cases  treated  with  serum 
and  67  without,  as  follows: 

Day  op  Treatment  on  which  the  Throat  was  Declared  Free  of 

Membrane. 


Day. 

Series  A,  without  serum. 

Series  B,  with  serum. 

Second    ....      4  cases  or    6  per  cent. 

1  case  or  1.08  per  cent 

Third 

13         "      20 

4  cases  or  4.3         " 

Fourth 

14         "      21 

9         "       9.8         " 

Fifth 

14         "      21 

18          "      19.5 

Sixth 

8         "      12 

18          "      19.5 

Seventh 

6          "        9        " 

10          "      10.8 

Eighth 

5          "        7.4     " 

2          "       2.1 

Ninth 

1  case  or    1.5    " 

1  case  or  1.08       " 

Tenth 

1         "        1.5     " 

1         "       1.08 

Eleventh 

1         "        1.5     " 

0         "       

Twelfth  . 

2  cases  or  2.1         " 

Thirteenth 

2          "       2.1          " 

Fourteenth 

2          "        2.1 

Seventeenth 

1  case  or  1.08       " 

Twenty-fourth 

1         "       1.08 

Twenty-eighth 
Thirty-ninth 

1         "       1.08        " 

1         "       1.08 

74   +   18   = 


The  author  of  this  table  says:     "In  Series  A  this  fact  (the  day  on 
which  the  membrane  disappeared  from  the  throat)  was  noted  in  only 


77//';  HNIiUM  7'n/<:ATMl'!NT  OF  1)1 1'llTII EHIA  74] 

67  of  the  cases,  and  in  02  in  Scries  li.  Only  I  occnrntfJ  (in  Scries  Aj 
in  which  membrane  reappc^arccJ,  and  that  on  the  foijrtccnt}i  day  after 
a(hnission;  whereas,  in  Series  B  there  were  5  cases  of  reappearance, 
18  cases  in  which  d(>ath  occurred  Ix^forc;  it  hiid  cleared  entirely,  anri  in  1 
case  it  was  observed  as  lat<!  as  the;  thirty-ninth  day  after  admission, 
and  the  forty-first  day  of  the  disease." 

Antitoxin  in  Laryngeal  Diphtheria. — iMany  observers  believe  that 
antitoxin  is  more  nseful  in  laryngeal  diphth(;ria  than  in  any  other 
variety.  But,  as  faucial  or  nasal  di|)htheria  is  more  fref|ucntly  followed 
by  toxaemia,  it  would  seem  that  the  serum  treatment  shouhl  be  most 
efficacious  in  these  forms  of  the  disease.  There  is,  however,  no  lack 
of  evidence  to  prove  that  the  mortality  rate  of  membranous  croup  has 
been  greatly  lessened  since  the  advent  of  antitoxin. 

In  1S93  von  Ranke  reported  1445  intubation  cases  of  laryngeal 
diphtheria  with  a  death  rate  of  02.5  per  cent.  Later,  with  antitoxin, 
he  treated  342  similar  cases  with  a  reduced  death  rate  of  28.9  per  cent. 

In  Baginsky's  service,  in  1895,  during  a  period  of  two  months  when 
the  serum  could  not  be  obtained,  there  were  116  cases  of  laryngo- 
stenosis,  with  a  death  rate  of  62.2  per  cent.;  while  with  the  serum 
treatment,  just  before  and  immediately  after  this  involuntary  pause, 
the  mortality  was  37.8  per  cent. 

Kronlein  (Zurich),  in  his  report  to  the  Twenty-seventh  Congress  of 
German  Surgeons  (1898),  showed  that  previous  to  the  use  of  antitoxin 
about  one-half  of  all  the  croup  cases  observed  in  the  clinical  hospitals 
of  the  university  had  to  be  operated  upon,  but  from  the  use  of  this 
agent  the  proportion  has  fallen  to  23.1  per  cent.  While  the  average 
mortality  among  the  operated  (tracheotomy  or  intubation)  cases  was, 
formerly,  66.1  per  cent.,  it  has  been  reduced  to  35.6  per  cent. 

The  Committee  of  the  American  Pediatric  Society  on  the  "  Collective 
Investigation  of  the  Antitoxin  Treatment  of  Laryngeal  Diphtheria  in 
Private  Practice,  1896-97,"  arrived  at  the  following  conclusions:  "First, 
that  before  the  use  of  antitoxin  it  was  estimated  that  90  per  cent,  of 
laryngeal  diphtheria  cases  required  operation;  whereas  now,  with  the 
use  of  antitoxin,  39.21  per  cent,  require  it.  Second,  that  the  percentage 
figures  have  been  reversed;  formerly  27  per  cent,  approximately  repre- 
senting the  recoveries,  while  now,  under  antitoxin,  27  per  cent,  repre- 
sents the  mortality." 

Dr.  J.  S.  Billings,  Jr.,^  presents  the  following  tabulation  of  cases 
of  laryngeal  diphtheria,  operative  and  non-operative,  treated  in  New 
York  City  with  antitoxin  by  various  physicians,  from  October  1,  1895, 
to  January  1,;1903: 

1  New  York  Medical  Journal  and  Philadelphia  Medical  Journal,  December  12, 1903. 


742 


DIPHTHERIA 


Laryngeal  cases. 

Non-operative  cases. 

Operative  cases. 

Cases. 

Deaths. 

Mortality 
per  ecnt. 

Cases. 

Deaths. 

Mortality 
per  cent. 

cases.  Deaths.  Mortality 

Moribund  cases  \ 
deducted.    .    ./ 

2504 
319 

629 
319 

25.1 

1843 
211 

389 
211 

21.1 

661 
108 

240 
108 

36 

Remain     .    . 

2185 

310 

14.2 

•1632 

178 

10.9 

553 

132 

23 

Goodall,  of  London,  published  in  the  British  Medical  Journal,  1899, 
voh  i.  p.  197,  the  following  interesting  statistics: 

Cases  of  Laryngeal  Diphtheria  Tracheotomized  and  Treated 
WITHOUT  Antitoxin, 

Authority. 
Sanne  hopital  des  enfants  malades 
Sanne  (hopital  Sanne  Eugiene)  . 

E.  Hirsch 

Antitoxin  Com.  of  Clinical  Society 
Asylum  Boards  Hospital,  1889-1893 

"  "  "  1894    . 

Cluhbe  (Sydney  Children's  Hospital) 
Guersant        ..... 
Eastern  Hospital,  1892-1893 


Cases. 

Recoveries. 

Recoverj 

2351 

6901 

29.3 

2312 

5992 

25.4 

1654 

517 

31.2 

1531 

434 

28.3 

323 

104 

32.1 

261 

77 

29.5 

199 

64 

32.0 

156 

28 

18.0 

140 

30 

21.4 

8927 


2543 


28.4 


Cases  of  Laryngeal  Diphtheria  Tracheotomized  and  Treated 
with  Antitoxin. 

Authority.                                         Cases.  Recoveries.      Recovery  per  ct. 

Asylum  Boards  Hospital 680  384  56.4 

American  Pediatric  Society         .        .        .        .    668  486  72.7 

Collected  by  Welch  (W.  H.)  from  39  reports      .    518  ,                313  60.4 

Belin,  Strassburg 132  88  66.6 

Clubbe,  Sydney 129  80  62.0 

Roux .        .    121  65  53.7 

University  College  Hospital         ....      72  53  73.6 

Cerne  (Frankfort) 54  37  68.4 

2374  1506  63.4 


In  the  Willard  Parker  Hospital,  New  York,  the  mortality  among 
the  intubation  cases  of  membranous  croup  continues  high  in  spite  of 
the  antitoxin  treatment.  Through  the  courtesy  of  Dr.  Louis  Fischer, 
one  of  the  attending  physicians  to  the  hospital,  we  are  able  to  present 
the  results  for  the  years  1901-2-3,  as  follows: 

Year.  Intubation  cases.  Deaths.  Mortality  per  ct. 

.1901  ■.!       .        ■.     ■  .        .••.-.        .        .        .222  152  68.47 

1902 258  142  55.04 

1903 352  229  65.06 

Total 832  523  62.87 


1  Including  76  cases  discharged  uncured. 
-  Including  90  cases  discharged  uncured. 


77//';  HI<:iiUM  TliF.ATMENT  Oh'  1)1 1'll'I'll FJU A 


743 


In  the  Municipal  Hospital  of  Philadclpliia  the  inortality  rate  among 
intubation  cases  of  larynfjjciil  (lif)litlicria  also  confiTincs  liigli,  as  may  be 
seen  in  the  followiiiiji;  table: 


Year. 
1894. 
1895. 
1896. 
1897. 
1898. 
1899. 
1900. 
1901. 
1902. 
1903. 


Iiiluhdlioii  caHes. 


Without  antitoxin 100 

About  no  per  ct.  ol'  the  cuses  received  aiitiioxin  V12^ 

With  antitoxin l.W-' 

182 

149 

16.5 

202 

13!) 

110 

"  110 


iJeathB. 

7.5 

f.7 

94 
127 
104 

97 
111 

GR 

hA 

55 

850 


Mortality  perct. 
75.0 
54.91 
60.25 
69.78 
69.99 
58.78 
54.95 
47.47 
49.09 
50.0 

59.23 


The  average  rate  of  mortality  among  the  above  cases  since  anti- 
toxin has  been  employed  is  58.05  per  cent.  There  has  been  no  deduction 
in  either  series  in  the  case  of  patients  admitted  moribund  or  when 
believed  to  be  beyond  hope,  as  is  the  practice  in  some  other  hospitals. 

Dr.  J.  H.  McCoUom,  of  the  South  Department  Hospital,  Boston, 
furnishes  the  following  table  showing  the  number  of  cases  of  laryngeal 
diphtheria  treated  by  intubation  in  the  Boston  City  Hospital,  proper, 
and  in  the  South  Department,  from  1888  to  1903,  inclusive: 


Preantitoxin  Period. 

Antitoxin  Period. 

No.  of 

Per  cent. 

No.  of 

Per  cent. 

Year. 

intubation 

Deaths. 

of 

Year. 

intubation 

Deaths. 

of 

cases. 

inortality. 

cases. 

mortality. 

1888    . 

.    100 

78 

78.00 

1895    . 

.    118 

64 

54.23 

1889    . 

.    128 

104 

81.25 

1896    . 

.    224 

145 

64.73 

1890    . 

.      93 

79 

84.94 

1897    . 

.    146 

67 

45.88 

1891    . 

.      50 

42 

84.00 

1898    . 

.      71 

42 

59.15 

1892   , 

.      65 

56 

86.15 

1899     . 

.    192 

63 

32  81 

1893    . 

.    109 

90 

82.56 

1900     . 

.     259 

87 

33.59 

1894    . 

.      89 

74 

88.14 

1901     . 

.     184 

58 

31.52 

1902     . 

.    145 

49 

33.79 

1903     . 

.     139 

37 

26.61 

Total 


634 


82.49 


This  table  shows  that  the  former  death  rate  of  82.49  per  cent,  of 
laryngeal  diphtheria  treated  by  intubation  in  the  above-named  hospital 
has  been  reduced  to  41.40  per  cent,  since  the  emplo\inent  of  antitoxin. 

Results  in  Diphtheria  (including  Membranous  Croup).— "We  have 
just  referred  to  the  results  of  antitoxin  in  larjugeal  diphtheria,  and  will 
now  speak  of  its  results  in  diphtheria  in  general. 

In  1897  Rauchfiiss^  communicated  to  the  Twelfth  International 
Medical  Congress,  at  Moscow,  the  most  extensive  statistics  that 
have  yet  been  collected  on  the  subject  of  serum  therapy  in  diph- 
theria.    They  give  the  results  of  the  enquiry  throughout  the  Empire 

1  Of  those  which  received  antitoxin  the  death  rate  was  52.94  per  cent. 

2  Twenty-four  of  this  number  did  not  receive  antitoxin. 

3  Quoted  by  Bayeux,  La  diphtheric,  Paris,  1899. 


744 


DIPHTHERIA 


of  Russia  undertaken  by  the  Pediatric  Society,  and  the  Society  of 
Russian  Physicians  at  St.  Petersburg.  The  figures  include  44,631 
cases,  all  of  which  refer  to  positive  cases  of  diphtheria.  They  were 
secured  from  fifty-one  of  the  eighty-nine  governments  and  districts 
of  Russia,  and  are  as  follows: 


Diphtheria  treated  without 
antitoxin. 


Diphtheria  treated  with 
antitoxin. 


Years. 

Cases. 

Deaths. 

Per  cent. 

Cases. 

Deaths. 

Per  cent 

1895    . 

.    4521 

1424 

31.4 

19,619 

3163 

16.1 

1896     . 

.    ■  991 

460 

46.4 

19,630 

2684 

13.6 

1896-1897    . 

.      995 

335 

33.6 

5,382 

675 

12.5 

Total 


44,631 


14.6 


We  notice  here  a  reduction  from  34.1  per  cent,  to  14.6  per  cent,  by 
the  serum  treatment. 

The  following  table  shows  the  comparative  mortality  from  diphtheria 
in  the  Russian  hospitals  before  and  since  the  advent  of  serum  therapy. 
The  figures  are  based  upon  the  official  report  of  Dr.  S.  Ippolitow  on 
Serotherapy  in  Russia:^ 

Diphtheria  Treated  in  Russian  Hospitals. 


Years 

No.  of  cases. 

Deaths. 

Mortality  per  ct 

1887 

(without  antitoxin) 

.      6,115 

1,832 

30.0 

1888 

.      6,546 

1,964 

30.0 

1889 

.      6,214 

1,732 

27.9 

1890 

.      6,940 

1,971 

28.4 

1891 

.      7,252 

1,878 

26.6 

1892 

.      7,023 

2,175 

31.0 

1893 

.      8,493 

2,692 

31.7 

1894 

.     12,068 

3,560 

29.5 

Total    . 

.     60,651 

17,804 

29.38 

1895 

(with  antitoxin)    . 

.     18,116 

3,550 

19.6 

1896 

"            "            . 

.     16,638 

2,438 

14.5 

Total    . 

.     34,754 

5,988 

17.22 

The  above  table  shows  that  the  average  mortality  before  the  serum 
treatment  was  29.38  per  cent.;  since  the  serum  treatment,  17.22  per  cent. 

We  think  it  proper  to  state  what  Prof.  Kassowitz,  of  Vienna,  has 
said  of  the  mortality  from  diphtheria  in  St.  Petersburg.  In  a  second 
paper  on  the  diphtheria  serum  question,  he  reiterates  his  former  views, 
and  by  means  of  charts  and  statistics  endeavors  to  maintain  his  position 
that  antitoxin  is  of  little  if  any  therapeutic  value.  He  presents  statistics 
which  we  tabulate,  as  follows: 


1  Medical  Department  of  the  Russian  Ministry  of  the  Interior. 
-  Therapeutische  Monatshefte,  1902,  vol,  xvi.  p  499. 


77//';  HFJtUM   TUKATMKNT  Oh'  1)1 1'lllll i:i! I  \ 


74; 


Diphtheria  Moktamiy  in  Sr.  I'f/i  khhiutkg. 


Preantltoxln  Period. 

Antitoxin  I'erUxl. 

Deaths  In  each 

OeathH  In  each 

Years. 

DCRtllK. 

10,000  of 
poimliitioii. 

YeJirw. 

DcathK. 

10,000  of 
[K)|)Ulatlon. 

1801 

.      34!) 

3.0 

189.') 

.      807 

8..') 

l.Sl)2 

.      333 

3.5 

iHw; 

.     1188 

11.6 

18<)3 

.      378 

3.9 

1897 

.     1949 

20.5 

1894 

.     1027 

10.8 

1898 

.     1350 

12.0 

1899 

.     1090 

9.7 

1900 

.     1134 

10.0 

1901 

.     14:J4 

12.7 

Average 


522 


5,4 


Average 


1272 


Kassowitz  says:  "The  diplithcria  mortality  that  has  maiiitaincfl 
itself  at  so  fearful  a  height,  as  in  fact  it  has  in  St.  Petersburg  during 
the  past  seven  years  under  the  beneficent  influence  of  the  serum  treat- 
ment, was  exceptional  even  before  the  days  of  the  s(>rurn  application." 

Kassowitz  reproduces  graphic  charts  from  an  article  published  by 
de  Maurans/  in  which  it  is  shown  that  the  mortality  from  diphtheria 
in  Birmingham,  Liverpool,  Dublin,  and  Stockholm  has  strikingly  risen 
during  the  serum  period.  The  rise  began  in  some  instances  a  year  or 
so  before  the  use  of  serum  and  in  others  after  its  use. 

This  writer  still  further  shows  that  the  curves  of  diphtheria  mortality 
were  not  influenced  by  the  introduction  of  serum  treatment  in  Budapest, 
Glasgow,  Zurich,  Lille,  Cologne,  Berne,  Christiana,  Beriin,  Lyons, 
Brussels,  Leipzig,  Edinburgh,  Paris,  Geneva,  Copenhagen,  Havre, 
Nantes,  Toulouse,  Turin,  Antwerp,  Stuttgart,  Munich,  Hamburg, 
Buenos  Ayres,  and  London. 

As  tending  to  show  the  inutility  of  antitoxin,  Kassowitz  says  that  in 
1897,  according  to  the  German  Imperial  Board  of  Health  Reports,  42.9 
per  cent,  of  those  who  died  of  diphtheria  were  given  serum  within  three 
days  of  the  onset  of  the  disease,  and  22  per  cent,  within  two  days. 

The  value  of  the  antitoxin  treatment  is  forcibly  demonstrated  in  the 
reports  of  the  Metropolitan  Asylums'  Board.  In  1894,  3042  patients 
of  all  ages  were  treated  without  serum,  in  the  hospitals  controlled  by 
the  Board,  with  902  deaths — a  death  rate  of  29.6  per  cent.  In  1895, 
the  first  year  of  the  serum  treatment,  3529  patients  were  thus  treated, 
with  a  death  rate  of  22.5  per  cent.  This  shows  a  fall  in  the  mortality 
of  7.1  per  cent.  In  the  annual  report  of  the  Metropolitan  Asylums' 
Board  for  1901,  it  appears  that,  in  that  year,  (i499  cases  of  diphtheria 
were  treated  with  antitoxin  in  the  Board's  hospitals,  with  817  deaths — 
a  death  rate  of  12.5  per  cent.  There  has,  therefore,  been  a  reduction 
in  the  mortahty  from  29.6  per  cent,  in  1894,  without  antitoxin,  to 
12.5  per  cent,  in  1901,  with  antitoxin.  The  treatment  in  other  respects 
is  said  to  have  been  the  same. 

According  to  this  report,  the  laryngeal  cases  treated  in  the  Board's 
hospitals  in  1901  with  antitoxin  numbered  753,  of  which  number  159 
died,  yielding  a  death  rate  of  only  21.1  per  cent. 


1  Semaine  modicale,  1901,  p.  401. 


746 


DIPHTHERIA 


Goodall/  of  London,  presents  the  following  compilation  of  statistics 
from  reports  of  the  statistical  committee  of  the  Metropolitan  Asylums' 
Board,  showing  the  case  mortality  of  the  city  of  London,  before  and 
since  the  advent  of  antitoxin: 


Mortality  per  cent,  of  all  notified  cases 

Mortality  per  cent,  of  notified  cases  admitted  to ) 
Asylums'  Board  hospitals J 

Mortality  per  cent,  of  notified  cases  not  admitted 

Per  cent,  of  notified  cases  admitted  to  hospitals 


Before  antitoxin. 


1892         1893         1894 


23.8 

24.8 

21.5 
30.1 


24.8 

27.1 

23.7 
24.5 


24.7 

25.0 

24.5 
38.8 


Since  antitoxin. 


1895         1896         1897 


21.2 

18.3 

23.3 
41.5 


19.9 

17.7 

21.3 
39.9 


17.4 

14.9 

20.1 
51.4 


Goodall  also  shows  the  case  mortality  of  diphtheria  treated  in  the 
hospitals  of  the  Metropolitan  Asylums'  Board,  as  follows: 


Table  I. 

1892.        1893.        1894.         1895.        1896. 

29.5        30.4        29.2  22.8        21.2 

"  Later  years  contain  larger  number  of  adults." 


1897. 
17.6 


Table  II. — Mortality  in  children  under  five  years  of  age. 

1892.        1893.        1894.         1895.        1896.        1897. 

51.5        53.3        43.9  39.5        30.3        24.9 

"  Including  fatalities  from  other  diseases  combined  with  or  following  diphtheria." 

The  annual  reports  on  the  work  of  the  Metropolitan  Asylums'  Board 
for  the  year  1903  show  that  the  Board  received  during  the  year  notifica- 
tions of  7582  cases  of  diphtheria;  of  these  5072  were  treated  in  the 
hospitals,  with  a  death  rate  of  only  9.6  per  cent.  The  average  death 
rates  in  the  Board's  hospitals  in  quinquennial  periods  since  the  year 
1887  are  as  follows: 


1887  to  1891. 
33.6  per  cent. 


1S92  to  1896. 
25.5  per  cent. 


1897  to  1901. 
13.7  per  cent. 


1902  and  1903. 
10.4  per  cent. 


According  to  a  pamphlet  issued  by  the  authorities  of  the  Institute 
for  Infectious  Diseases,  of  Japan,  the  serum  treatment  of  diphtheria 
has  affected  the  statistics  of  this  disease  in  that  country  as  follows: 
Previous  to  the  sale  of  serum  the  average  death  rate  of  diphtheria 
patients  was  50  per  cent.;  but  since  the  sale  began  it  has  gradually 
decreased  to  38  per  cent,  in  1896,  36  per  cent,  in  1897,  and  finally  as 
low  as  28  per  cent,  in  1902.^ 

Most  of  the  statistics  collected  in  this  country  are  equally  positive 
as  showing  the  value  of  antitoxin  in  the  treatment  of  diphtheria.    The 

1  British  Medical  Journal,  1899,  vol.  i.  p.  197. 

2  It  is  surprising  to  note  in  this  pamphlet  that,  while  the  death  rate  from  diphtheria  in  Japan  has 
been  greatly  reduced  since  the  advent  of  antitoxin,  there  has  been  a  large  increase  of  both  cases 
and  deaths  annually, 


Till':  ^i<:uiiM  Tui:ATMi<JN'r  OF  i>ii'irriih:niA  747 

comparative  mortality  from  this  disease  in  (^liiea^o,  l)cJV>n'  and  aft<'r 
the  introchietion  of  tlie  serum  treatment,  as  shfjwn  in  tlic  linllcliit  of 
February  13,  1004,  of  the  Health  I)<'[)artment  of  that  eity,  is  as  follows: 
During  the  preantitoxin  period  the  deaths  amujally  J)er  10,000  of 
population  were  12.4r)  j)er  cent.,  while  since  the  serum  has  been  uscfj 
the  ratio  of  deaths  has  been  reduced  to  4.55  per  cent.  'J'hc  increase  of 
population  amounts  to  52  per  cent.;  the  decrease  of  diphth(;ria  deaths, 
63.4  per  cent.  Between  ()ctol)er  5,  1895  (date  of  first  case  treated) 
and  December  31,  1003,  th(>  Tlealtli  Department  treated  7435  ca.ses  of 
bacterially  verified  (Jiphtheria,  of  which  number  470  died,  yielding  a 
death  rate  of  6.44  per  cent.  It  is  stated  that  the  average  mortality 
without  antitoxin  still  remains  about  35  per  cent. 

We  are  indebted  to  Dr.  J.  H.  McC-ollom,  of  Boston,  for  the  following 
table,  showing  the  ratio  of  m()rl)idity  and  of  the  mortality  of  diy)htheria 
in  Boston,  per  10,000  of  population, for  ten  years — 1S04  to  1003  inclusive: 

^,       ,  ^.  „  Ratio  of  T^     ^u  Ratio  of 

Years.  Population.  Cases.  ,.,.,  Deaths.       _     .  ,» , 

morbidity.  mortality. 

1894  ....  4«6,830  3019  61.01  878  18.03 

189.5  ....  501,083  4059  81.00  654  11.73 

1896  ....  516,305  4489  86.94  572  9.80 

1897  ....  528,912  3398  64.24  -456  7.77 

1898  ....  £41,827  1661  30.65  185  3.15 

1899  ....  555,057  2836  51.08  304  4.99 

1900  ....  560,892  4977  88.73  537  9.57 

1901  ....  573,579  3319  57.86  353  6.15 

1902  ....  588,741  1940  34.72  225  3.82 

1903  ....  600,929  2091  34.79  211  3.51 

McCollom  says  the  South  Department  Hospital  of  Boston  was  opened 
for  patients  September,  1895,  and  antitoxin  has  been  given  to  every 
case  of  diphtheria  admitted.  In  1896  he  published  the  following  table, 
which  shows  the  number  of  patients,  by  ages,  admitted  to  the  hospital 
from  September  1, 1895,  to  May,  1896,  together  with  the  mortaUty  rate  in 
each  age  period: 

Age.  Cases.  Deaths.  Mortality  per  ct. 

Under    1  year 17                       3                     17.64 

1  to     2  years 74                     20                     27.02 

2  "      3      " 136                      37                       27.2 

3  "      5      " 329                      55                       16.71 

5    "     10      " 410                      39                        9.51 

10     "    20      " 189  9  4.76 

20  years  aud  upward 206  7  3.38 

1359  170  12.5 

In  presenting  these  statistics  McCollom  says  that  from  February, 
1891,  until  February,  1894,  there  were  1062  cases  of  diplitheria,  with 
493  deaths — a  death  rate  of  46.42  per  cent. 

The  cases  treated  in  the  South  Department  Hospital,  Boston,  since 
the  introduction  of  antitoxin  have  vielded  the  following  annual  mortalitv : 


748  DIPHTHERIA 

Year.  Cases.  Deaths.        Mortality  per  ct. 

1895 844                      96  11.37 

1896 1,779                    276  15.54 

1897 1,291                     181  14.02 

1898  : 892                    103  11.54 

1899 .     1,672                    180  10.78 

1900        ?        .        .        «       .        .  '       .        .     2,600                    294  11.3 

1901 '  .        .     1,448                    172  11.87 

1902 1,018                     103  10.11 

Total 11,544  1405  12.17 

In  an  interesting^  paper  detailing  the  results,  of  antitoxin  in  New  York 
City  in  1902,  by  Dr.  J.  S.  Billings,  Jr./  the  following  diagram  appears: 


TABLE  SHOWING   DEATH  RATE  PER    (0,000 

FROM   DIPTHERIA  IN  THE  BOROUGHS 

OF  MANHATTNaN  and  the  BRONX 

FROM   1888  TO  1902 

YEAR 

64 

1888  89    90    91    92    93    94    95    9fi    97    98    99  1900  01    20 

18 

GO 

17 

S 

50 

\, 

16 

52 

>-    48 
^44 
< 

H    40 
a: 
1    36 

UJ    32 
en 

<    28 

^^   24 

20 

IG 

12 

\ 

15 
o 

14  § 

o 

13  -- 

tc 
12  u. 

11    UJ 

1- 
10  < 

9  I 

1- 

82 
7^^ 
6 

\ 

A 

z 

\ 

/ 

/  \ 

\s 

4 

\< 

\ 

/ 

\ 

K' 

N 

LU 

\^ 

V 

^ 

ID 

K 

> 

\ 

o 

\, 

3 

\ 

\ 

O 

K 

\ 

z 

V- 

-^ 

Y^ 

^ 

-^ 

^ 

6^ 

Lv 

\ 

8 

4. 

DOTTED. --CASE  MORTALITY 
SOLID DEATH  RATE 


l^his  diagram  shows  in  a  very  striking  manner  how  greatly  the  mor- 
tality from  diphtheria  in  New  York  City  has  diminished  since  the 
introduction  of  the  serum  treatment. 

After  presenting  considerable  statistical  evidence,  Billings  concludes 
his  paper  by  saying:  "There  is  no  longer  any  doubt  as  to  the  curative 
action  of  antitoxin  in  diphtheria.  Of  15,792  cases  injected  with  anti- 
toxin furnished  free  of  charge  by  the  Department  of  Health  or  by  its 
inspectors,  1860  died,  a  case  fatality  of  11.8  per  cent.  If  the  cases 
moribund  when  injected  (722  in  number)  are  deducted  the  case  mortality 
is  further  reduced  to  7.5  per  cent." 


1  New  York  Medical  Journal  and  Philadelphia  Medical  Journal,  December  12, 1903. 


Tiii<:  si'Ua/M  Tui<:ATMi<JN'r  Of''  hiriiriiijn  \ 


74tJ 


The  statistics  of  \\\v  Willard  Parker  Hospital,  however,  show  j)raeti- 
eally  no  i-cMhietion  now  over  the  prearititoxiii  [>erio(J.  We  are  infi<l)terj 
to  Dr.  Louis  I^'iseher,  one  of  the  attending  pliysieians  to  the  [losj^ital, 
for  t^e  (lata  in  the  following  table: 


loHI'/'l  Al- 


Casus  of  Dii'HTniouiA  Thkaiki)  in  tmk  Wiij.ahi)  Parkiok  il< 
New  York  City,  vwm  1880  to  VM)'.',. 

Antitoxin  J'erio'l. 


Year. 

1889 
1890 
1891 
1892 
1893 
1894 


rreaiititoxin  Period 
Cases.    Deaths 


391 
311 
303 
311 

357 
732 


70 

r,7 

85 

79 

108 

205 


Total 


2405         623 


Mortality 
per  cent. 

20,20 

21.54 

28.05 

25.40 

30.25 

28.01 


25.9 


Year, 

1895 
1896 
1897 
1898 
1899 
1900 
1901 
1902 
1903 


Total 


Cases.  Deaths. 

190 
205 
214 
109 
192 
238 
275 
271 
356 


825 
860 
881 
612 
781 
823 
919 
1112 
1281 


8094  2050 


Mortality 
per  cent. 
23.05 
23.84 
24.29 
17.81 
24.58 
28.92 
29.92 
24.37 
27.79 

25.32 


The  following  table  relates  to  the  cases  of  diphtheria  treated  in  the 
Municipal  Hospital  of  Philadelphia  from  1890  to  1903,  inclusive: 


Preantitoxin  Period. 


Year. 

1890  . 

1891  , 

1892  . 

1893  . 

1894  . 


Cases 

.    Deaths. 

Mortality 
per  cent. 

Y'ear. 

12 

3 

25.00 

1895 

29 

1 

3.44 

1896 

183 

48 

26.22 

1897 

217 

62 

28.57 

1898 

465 

154 

33.12 

1899 
1900 
1901 
1902 
1903 

Total  . 


906 


268 


29.58 


Total 


Antitoxin  Period. 

Cases. 

Deaths. 

Mortality 
per  cent. 

.      706^ 

190 

26.91 

.      869 

193 

22.2 

.     1295 

300 

23.16 

.     1229 

297 

24.16 

.     1373 

275 

20.02 

.     1299 

264 

20.31 

.      889 

174 

19.57 

.      601 

137 

22.79 

.      746 

170 

22.78 

.     9007 

2000 

22.2 

This  table  shows  a  mortality  reduction  in  favor  of  the  antitoxin 
period  of  7.38  per  cent. 

There  is  no  dearth  of  evidence  to  prove  that  the  early  administration 
of  antitoxin  is  important  if  its  real  advantages  are  to  be  gained.  Dr. 
MacCombie's^  results  at  the  Brook  Hospital,  London,  show  this  in  a 
very  convincing  manner.  During  the  past  seven  years  (1897  to  1903 
inclusive)  the  total  number  of  cases  of  diphtheria  treated  in  that  hospital 
with  antitoxin  has  been  4812  witliout  a  single  death  occurring  among 
those  injected  on  the  first  day  of  the  disease.  The  following  table  shows 
these  cases  arranged  according  to  the  dav  of  disease  on  which  the 
serum  was  injected,  showing  the  mortality  per  cent,  each  year: 


1  Only  about  one-half  of  these  cases  received  antitoxin. 
-  Metropolitan  Asylums  Board's  Annual  Report  for  1903. 


750 


DIPHTHERIA 


Cases  (187),  first  day,  mortality  was  . 
Cases  (1186),  second  day,  mortality  was 
Cases  (1233),  third  day,  mortality  was  . 
Cases  (963),  fourth  day,  mortality  was 
Cases  (1260),  fifth  day  and  after,  mortality  was 


1897.  1898. 

0.0  0.0 

5.4  5.0 

11.5  14.3 


0.0 
3.8 
12.2 


1900.  1901.  1902.  1903. 
0.0   0.0   0.0   0.0 


3.6 
6.7 


4.1   4.6 
11.9   10.5 


19.0   18.1   20.0   14.9   12.4   19.8 
21.0   22.5   20.4   21.2   16.6   19.4 


4.2 
17.6 
16.07 
17.3 


The  Bulletin  issued  by  the  Health  Department  of  Chicago,  February 
13,  1904,  contains  a  record  of  7435  cases  of  diphtheria  arranged  accord- 
ing to  day  of  disease  on  which  antitoxin  was  administered,  showing  the 
mortahty  per  cent.    This  data  appears  in  the  following  table: 


Day  of  disease  on  which  antitoxin  was  injected 
First  day 
Second  day  . 
Third  day     .        ... 
Fourth  day  .       ... 
Later  than  fourth  day 

Total 


Cases. 

586 
1913 
2624 
1374 

936 

7433 


Deaths. 

2 

28 

85 

148 

216 

479 


Mortality  per  ct. 
0.34 
1.46 
3.24 
10.8 
23.1 

6.44 


Among  these  7435  cases  there  were  included  608  intubated  laryngeal 
cases,  of  which  100  died — a  death  rate  of  only  16.44  per  cent. 

It  is  also  stated  in  the  report  of  the  Commissioner  of  Health  of  Chicago 
that  there  were  7051  exposed  persons  who  were  immunized  with  500 
units  each;  of  these  46  were  subsequently  attacked,  but  all  recovered.^ 

Park^  presents  the  following  table  showing  the  mortality  of  diphtheria 
treated  with  antitoxin,  including  10,425  cases,  arranged  according  to 
day  of  disease  on  which  treatment  was  commenced: 

Day  of  disease  on  which  antitoxin  was  injected.  Cases.  Deaths.  Mortality  per  ct. 

First  and  second  day 4,232  267                       6.3 

Third  and  fourth  day         ....  3,870  656                     17.2 

After  fourth  day 1,984  605                     34.6 

Day  unknown 339  44                     13.0 

Total        .        .        .        .        .     10,425  1672  16.0 

(Cases  moribund  or  dying  within  twenty-four  hours  included.) 

Billings'  presents  the  following  tabulation  of  cases  of  diphtheria  in 
which  antitoxin  was  administered  (1)  by  Inspectors  of  the  Department 
of  Health,  from  March  1, 1902,  to  January  1, 1903,  and  (2)  by  physicians 
(not  inspectors),  from  October  1,  1895,  to  January  1,  1903: 


1  American  Medicine,  February  27, 1904. 

2  Loomis-Thompson,  American  System  of  Practical  Medicine. 

3  New  York  Medical  Journal  and  Philadelphia  Medical  Journal,  December  12,  1903. 


Tiii<:  si<:h'i/M  TiacATMENT  or  i)ii'ii'rin:i;i  \ 


751 


(1)  Day  of  diHoaso  on  which  luiti toxin  wan  injt 

ctcd 

OaKCH 

First  (lay  : 

Total  ciiHCK       .... 

.      125 

No  rnoribniid  cascH. 

Second  day : 

Total  cases       .... 

.      3-10 

Five  inorihiind  cawea  deducted 

335 

Third  day  : 

Total  cases       .... 

320 

Six  moribund  cases  deducted 

:<H 

Fourth  day  : 

Total  cases       .... 

1,36 

Nine  moribund  cases  deducted 

127 

Fifth  day  : 

Total  cases       .... 

65 

Four  moribund  cases  deducted 

61 

Later  than  fifth  day  : 

Total  cases       .... 

71 

Five  moribund  cases  deducted 

66 

Unknown : 

Total  cases       .... 

10 

No  moribund  cases. 

Total  cases       .... 

1062 

Twenty-nine  moribund  cases  deducted  1033 

(2)  Day  of  disease  on  which  antitoxin  was  injected.  Cases. 

First  day : 

Total  cases 995 

Thirty-five  moribund  cases  deducted  .      960 

Second  day : 

Total  cases 2526 

Seventy-four  moribund  cases  deducted  2452 

Third  day  : 

Total  cases 1335 

Fifty  moribund  cases  deducted    .       .  1285 

Fourth  day : 

Total  cases 485 

Forty  moribund  cases  deducted  .       .      445 

Fifth  day  and  over : 

Total  cases ,      .      425  ■ 

Sixty-two  moribund  cases  deducted    .  363 

Unknown : 

Total  cases 440 

Twenty-one  moribund  cases  deducted     419 


licaths. 

Mortullly  r«<;r  cl 

2 

1.66 

15 

4.41 

10 

2.98 

22 

6.87 

16 

5.09 

19 

13.97 

10 

7.87 

10 

15.38 

6 

9.83 

11 

15.49 

6 

9.09 

10.0 


Total  cases       .... 
232  moribund  cases  deducted 


6206 
5924 


80 

7.53 

51 

4.92 

Deaths. 

Mortality  per  ct. 

62 

6.2 

27 

2.9 

179 

7.0 

105 

2.6 

150 

11.2 

100 

7.8 

107 

22.0 

67 

15.0 

121 

26.0 

59 

16.0 

54 

12.2 

33 

7.8 

673 

10.84 

391 

6.6 

At  the  Willard  Parker  Hospital  (New  York),  during  the  first  nine 
months  of  1895,  the  resuUs  were  as  follows:^ 

Day  upon  which  the  serum  treatment  was  begun.        Cases.  Mortality  per  cent. 

First  day 108  10.09 

Second  day        ...  130  25.19 

Third  day 116  34.19 

From  1895  to  1903  inchisive,  7469  cases  of  diphtheria  were  injected 
with  antitoxin  in  the  Municipal  Hospital,  Philadelpliia.  The  following 
table  shows  these  cases  arranged  according  to  day  of  disease  on  which 
the  antitoxin  was  administered,  shoAving  deaths  and  mortality  per  cent.: 


1  Winters,  Medical  Record,  June  20, 1896. 


Deaths. 

Mortality  per  cent. 

99 

10.32 

368 

15.82 

415 

23.56 

350 

31.56 

439 

33.38 

)eaths. 

Mortality  per  cent. 

20 

10.75 

66 

16.05 

81 

21.71 

145 

34.94 

137 

30.78 

752  DIPHTHERIA 

Day  of  disease  on  which  antitoxin  was  injected.    Cases. 

First  day 959 

Second  day 2325 

Third  day 1761 

Fourth  day 1109 

Later  than  fourth  day    ....    1315 

Total 7469  1671  22.37 

From  1894  to  1900  inclusive,  there  were  1830  cases  of  diphtheria 
admitted  to  the  Municipal  Hospital,  Philadelphia,  which  did  not 
receive  antitoxin.  In  the  following  table  these  cases  are  arranged 
according  to  day  of  disease  on  which  admission  to  the  hospital  occurred : 

Day  of  diseases  on  which  cases  were 
admitted  to  hospital. 

First  day 186 

Second  day .411 

Third  day 373 

Fourth  day 415 

Later  than  fourth  day   ....  445 

Total       .        .        .        .        .     1830  449  24.53 

In  taking  a  comparative  view  of  the  last  two  tables  the  showing  in 
favor  of  the  antitoxin  treatment  is  not  very  marked.  It  should  be 
understood  that  in  neither  of  these  series  of  cases  was  any  effort  made 
to  eliminate  those  admitted  moribund,  or  believed  to  be  hopeless,  or 
even  those  in  which  the  diphtheria  followed  in  the  wake  of  some  other 
affection,  like  measles  or  scarlet  fever.  The  history  in  each  case  as  to 
the  day  of  the  disease  on  admission  was  obtained  either  from  the  parents 
of  the  patient  or  from  the  patient  himself  when  old  enough.  It  is  not 
improbable  that  this  information  was  often  inaccurate.  But  histories 
as  to  duration  of  illness  are,  of  necessity,  almost  always  obtained  in 
this  way. 

We  must  confess  to  a  feeling  of  disappointment  in  the  results  obtained 
from  the  use  of  antitoxin  in  the  Municipal  Hospital.  We  had  fervently 
hoped  that  this  agent  would  effect  a  striking  reduction  in  the  mortality 
among  our  patients,  but  the  statistics  of  the  hospital  do  not  indicate 
any  great  saving  of  life.  The  reduction  in  the  death  rate  from  diph- 
theria in  the  hospital  has  at  the  most  been  about  7  per  cent.  It  may 
be  that  many  of  our  patients  are  received  at  too  late  a  period  of  the 
disease  to  respond  to  the  serum  treatment.  It  may  also  be  possible 
that  in  our  early  experience  with  antitoxin  the  serum  may  not  have 
been  employed  in  sufficiently  large  doses,  although  the  amount  given 
was  that  generally  advocated  at  the  time.  Park's  remarks  on  dosage 
in  animals  (extract  from  Pediatric  Section,  New  York  Academy  of 
Medicine,  November  10,  1904;  published  in  Archives  of  Pediatrics, 
December,  1904)  may  likewise  apply  to  the  human  subject.  Park 
states  that  a  given  amount  of  diphtheria  antitoxin  injected  into  an 
animal  immediately  after  a  fatal  amount  of  the  toxin  will  save  the  life 
of  the  animal.  If  a  delay  of  four  hours  occurs  before  the  injection  of 
the  antitoxin,  then  ten  times  the  amount  of  the  latter  is   necessary  in 


77//';  Hi'iiiiiM  ti{i<:a'I'MI':si'  of  i)ii'ii'riir:in  \  7o;i 

order  to  protect  tlu^  animal.  If  six  or  ci^lit  hours'  delay  occurs,  one 
hundred  times  the  amount  of  antitoxin  heroines  necessary.  Park  adds 
that  the  longer  one  waits  before  giving  (lie  ;intitoxin  the  greater  is  the 
chance  for  tlie  toxin  to  conihinc  nnd  enter  into  some  definite  rehition 
with  the  c(;lls. 

The  Paralysis  Incidence. — It  is  not  claimed  that  tlur  paralysis  inci- 
dence in  di[)htheria  has  been  lessened  by  antitoxin.  On  llie  erjntniry, 
it  is  believed  by  many  that  this  se<piela  is  more  fi'e(|iiently  seen  now 
than  formei-ly.  Baginsky  says  that  "paj'alysis  is  more  frecjuent  under 
antitoxin  than  before*;  perhaps  bec'ause  more  children  remain  alive." 

In  1000  cases  of  diphtheria  carefully  ol)served  hy  I>ennox  Hrowne 
he  found  that  paralysis  was  more  common  than  in  ])revious  years  when 
antitoxin  was  not  employed. 

Goodall,^  of  Ivondon,  lias  shown  that  paralysis  became  more  frcfjuent 
in  the  Metropolitan  Asylums'  Board  hospitals  after  the  introduction  of 
antitoxin.  He  presents  the  following  table  showing  the  percentage  inci- 
dence of  paralysis  in  the  Board's  hospitals  from  1S9.3  to  1897,  inclusive: 


Non-antitoxin. 
1893.         1894. 

189.i. 

Antitoxin. 

1896 

1897. 

Eastern  Hospital   . 

.    12.1 

10.8 

16.0 

21.4 

15.1 

Northwestern  Hospital 

.    14.0 

11.1 

18.9 

14.1 

12.8 

Western  Hospital  . 

.    18.1 

8.2 

17.7 

21.5 

11.0 

Southwestern  Hospital 

.    14.3 

18.3 

22.0 

20.6 

20.5 

Southeastern  Hospital . 

.     16.2 

20  2 

34.7 

42.3 

45.9 

Total. 

.    14.3 

13.2 

20.1 

21.3 

20.3 

Alleged  III  Effects  of  Antitoxin. — In  the  vast  majority  of  cases  no 
immediate  ill  effects  are  noticeable.  An  abscess  at  the  site  of  the 
injection  may  occur,  but  this  is  preventable. 

Many  observers  believe  that  antitoxin  has  increased  the  incidence 
of  nephritis.  It  does  seem  that  albuminuria  is  more  frequently  seen 
now  then  formerly.  Referring  to  the  results  in  his  1000  cases  of  diph- 
theria, Lennox  Browne  says  his  figures  show  a  very  considerable  and 
undoubted  increase  in  the  proportion  of  cases  of  nephritis  under  serum 
treatment  as  compared  with  the  old.  Speaking  of  Baginsky 's  experience 
to  the  contrary,  he  remarks:  "It  is  only  fair  to  quote  the  experience  of 
Professor  Baginsky.  .  .  .  On  a  comparison  of  993  cases  without 
serum  and  525  with  serum,  he  has  come  to  the  conclusion  that  the 
injection  of  serum  does  not  increase  the  frequency  of  nephritis.  gi\ing 
tables  in  support  of  his  contention.  This  observer  is  careful  to  give 
separate  and  widely  different  figures  for  clinical  nephritis,  as  distin- 
guished from  that  observed  post-mortem." 

Hansemann,  Washbourn,  Goodall,  and  T>ennox  Browne  have  noted 
the  liability  to  anuria  under  serum  treatment.  The  last-named  writer 
says  he  was  particularly  unfortunate  in  his  own  early  experience  in 
this  respect,  as  6  out  of  a  series  of  S  patients  died  Avith  anuria  as  the 
most  prominent  symptom. 

R.  W.  Marsden,"  of  London,  believes  that  the  early  use  of  antitoxin 

1  British  Medical  Journal,  1S99,  p.  197.  s  Ibid.,  1900,  vol.  ii.  p.  65S. 

4S 


754  DIPHTHERIA 

lessens  the  liability  to  albuminuria,  and  that  when  it  appears  late  in 
diphtheria  it  may  be  due  to  antitoxin.  He  says  that  "though  it  may 
have  an  irritant  effect  upon  the  kidneys,  yet  this  is  by  no  means  the  rule, 
and  in  any  case  its  action  is  only  temporary." 

Winters/  of  New  York,  one  of  the  attending  physicians  to  the  Willard 
Parker  Hospital,  believes  that  pneumonia  in  diphtheria  has  become 
mo]*e  frequent  since  the  employment  of  the  serum  treatment.  He  says 
that  "the  pneumonia  of  the  antitoxin  cases  of  diphtheria  differed  from 
the  pneumonia  we  were  in  the  habit  of  seeing  in  diphtheria;  that  it  was 
a  totally  different  disease  from  that' seen  before  in  the  course  of  diph- 
theria; that  it  occurred  as  a  sequela  and  not  as  a  complication."  He 
regards  it  as  septic  in  character. 

In  an  earlier  part  of  this  article  we  called  attention  to  the  frequency 
of  bronchopneumonia  in  the  laryngeal  form  of  diphtheria,  and  expressed 
the  belief  that  it  resulted  from  diphtheritic  involvement  of  the  respiratory 
tract.  It  is  true  that  bronchopneumonia  often  occurs  late  in  the  disease, 
and. even  at  times  during  convalescence  from  the  faucial  form  of  diph- 
theria, but  we  have  never  felt  that  it  was  due  to  the  serum  treatment. 

Before  concluding  it  may  be  well  to  mention  the  fact  that  more  than 
one  death  has  been  reported  as  immediately  following  the  injection  of 
the  serum.  This  accident  has  been  almost  entirely  confined  to  the  use 
of  the  serum  for  immunizing  purposes.  While  no  very  satisfactory 
explanation  has  been  given  for  the  occurrence  of  these  sudden  deaths, 
it  is  not  believed  that  they  were  caused  by  the  serum  fer  se. 

The  only  ill  effect  which  we  are  able  to  attribute  to  antitoxin  with 
any  degree  of  certainty  is  a  peculiar  exanthem,  often  attended  with  rise 
of  temperature  and  more  or  less  joint  pains. 

Antitoxin  Eruptions.  Frequency. — The  use  of  antitoxic  serum  in 
diphtheria  is  followed,  in  a  certain  proportion  of  cases,  by  a  train  of 
phenomena,  the  most  conspicuous  of  which  is  the  development  of  a 
cutaneous  eruption.  The  proportion  of  cases  in  which  antitoxin  rashes 
develop  is  most  variable.  Hartung  has  collected  from  the  literature  a 
series  of  2661  injections,  of  which  294,  or  11.4  per  cent.,  developed 
rashes.    253  of  these  eruptions  are  accounted  for  in  the  following  table: 

Eruptions.      Injections.  Per  cent. 

Heubner  (Berlin  cases) 54  298  ]8.1 

Heubner    ........     22  77  28,5 

Baginsky 49  525  9.3 

Soltmann 5  89  5.6 

V.  Ranke 5  118  4  2. 

Seitz |20  140  14.3 

I  4  180  2.22 

Forster 7  73  4  9.6 

Schucolty 4  38  10.5 

Gunther 3  33  9.0 

Bokai ;il  120  9.1 

<  30  147  20.4 

Moizard,  Paris 33  231  14  2 

Risel,  Halle 6  114  5.2 

253  22S-3  11.08 

1  Medical  Record,  June  20, 1896. 


Rflsh. 

Percent. 

18 

17 

■23 

2.'} 

19 

33 

22 

33 

77//';  SI'Jh'f/M   rUI'JATMMNT  Of  DI I'llTII IIRI A  755 

The  Imperial  Board  of  Health  of  Germany  reports  4358  cases  of 
diphtheria  injeeted  with  seru?n  from  January  to  July,  1805,  with  the 
production  ol"  354  rashes,  or  8.1  per  cent. 

Among  7S  cas(\s  of  diphtheria  treated  in  the  Scarlet  P'ever  and  I)ij)h- 
theria  Hospital  of  New  York,  in  lOOl,  rashes  occurred  in  25.4  per  cent. 

The  Investigating  Committee  of  the  Clinical  Society  of  London 
collected  records  of  663  cases;  220  of  these,  or  33.1  per  cent.,  develf>ped 
antitoxin  rashes. 

liCnnox  Brown(^^  noted  38  eruptions  in  UK)  cases.  Herg^ gives  the  follmv- 
ing  figures  for  the  Willard  Parker  llos})ital  of  New  Yoi-k  for  four  months : 

Canes. 

May 107 

June 103 

July 02 

August  .       , fi5 

Total 337  «2  24 

The  great  variability  in  the  frequency  with  which  antitoxin  eruptions 
develop  may  be  best  appreciated  when  it  is  stated  that  Monti,  of  \^ienna, 
observed  rashes  in  52  per  cent,  of  one  of  his  series  of  cases,  whereas 
Hager  did  not  observe  a  rash  in  a  single  instance  among  61  cases. 

In  our  own  experience  an  eruption  has  developed  in  about  20  per  cent, 
of  the  cases  injected. 

Date  of  Appearance  of  Eruption. — The  rash  may  appear  in  from 
one  day  to  one  month  after  the  injection  of  the  serum.  The  subjoined 
table  will  show  the  day  of  occurrence  of  120  antitoxin  eruptions  observed 
by  us  in  the  Municipal  Hospital  of  Philadelphia.  It  will  be  seen  that 
the  greatest  number  of  rashes  occurred  upon  the  sixth,  seventh,  and 
eighth  days  after  the  administration  of  the  serum.  Indeed,  by  actual 
computation  over  49  per  cent,  of  the  total  number  appeared  on  these 
days. 

The  date  of  appearance  of  the  rash  depends  much  upon  the  particular 
serum  employed.  A  few  years  ago  we  used  a  serum  the  rashes  from 
which  quite  uniformly  appeared  about  the  end  of  fourteen  days. 

Days  upon  which  Antitoxin  Eruptions  Developed  in  120  of  Our  Cases. 

Eash  appeared  in  1  case    on  the  second  day  after  the  serum  injection. 


6  cases 

fourth 

6      " 

fifth 

18      " 

sixth 

17      " 

seventh 

24      " 

eighth 

5      " 

ninth 

7      " 

tenth 

5      " 

eleventh 

7      *• 

twelfth 

5      " 

thirteenth 

5       " 

"        fourteenth 

1  case 

■'        fifteenth 

8  cases 

sixteenth 

3     " 

seventeenth 

1  case 

eighteenth 

1     ■' 

twentieth 

1  Diphtheria  and  its  Associates,  London,  1S95.        -  New  York  Medical  Record,  1S9S,  pp.  S65-S73. 


756  DIPHTHERIA 

In  the  report  of  the  Clinical  Society  of  London,  the  largest  number 
of  rashes  appeared  from  the  seventh  to  the  twelfth  day;  the  figures 
are  as  follows: 

Day  of  Appearance  of  Antitoxin  Eruptions. 

First  to  sixth  day 33  cases. 

Seventh  to  twelfth  day 147      " 

Thirteenth  to  eighteenth  day 34      " 

Nineteenth  to  thirty-first  day 6      " 

The  rashes  noted  by  I^ennox  Browne  appeared  for  the  greater  part 
from  the  seventh  to  the  twelfth  day.  The  statement  is  made  by  some 
writers  that  the  scarlatinoid  rashes  are  prone  to  occur  early,  in  the 
neighborhood  of  the  third  day.  We  have  seen  some  rashes  of  this 
character  occur  quite  early. 

Character  of  the  Eruption. — In  our  experience  the  vast  majority 
of  the  rashes  have  been  of  an  urticarial  character,  either  made  up  of 
frank  wheals  or  consisting  of  an  urticarial  erythema.  Next  in  frequency 
have  been  the  rashes  belonging  to  the  class  of  polymorphous  erythema. 

These  may  consist  of  irregular  marginated  and  non-elevated  patches 
of  redness,  or  may  show  a  distinct  tendency  to  annular  or  gyrate  con- 
figuration. It  is  not  uncommon  to  see  an  erythema  made  up  of  small, 
round,  red  patches  with  perfectly  pale  centres. 

In  other  cases  the  erythema  may  be  of  the  scarlatinoid  type  and  bear 
a  close  resemblance  to  the  exanthem  of  scarlet  fever.  These  appear 
to  have  occurred  much  more  frequently  in  New  York  City  than  in 
Philadelphia.  In  other  cases  the  rash  may  be  a  morbilliform  erythema, 
looking  not  unlike  the  eruption  of  measles. 

Vesicular  and  bullous  eruptions  are  quite  uncommon;  but  we  have 
observed  one  well-pronounced  case,  which  is  shown  in  the  accompanying 
photographs.  We  have  also  observed  a  case  in  which  there  was 
extravasation  of  blood  into  the  vesicles.  Purpuric  antitoxin  eruptions 
are  not  very  frequent,  for  of  many  hundreds  of  rashes  that  have 
occurred  in  the  Municipal  Hospital  we  have  seen  not  more  than  eight 
or  ten  characterized  by  hemorrhage  into  the  skin. 

Antitoxin  eruptions  are  frequently  polymorphous,  exhibiting  wheals, 
patches  of  non-elevated  erythema,  and  occasionally  papules  and  vesicles. 
Mixed  urticarial  and  erythematous  lesions  are  frequently  obserA'ed. 

Indeed,  all  of  the  lesions  which  may  occur  in  erythema  multiforme 
may  be  present  in  the  rashes  following  serum  injections.  Most  of  the 
rashes  are  accompanied  by  severe  itching;  this  is  particularly  complained 
of  by  adults,  who  are,  perhaps,  better  able  to  give  expression  to  their 
discomfort. 

(Edema  of  the  skin  is  commonly  noted  in  association  with  antitoxin 
rashes.  The  face  is  puffed,  particularly  about  the  eyelids,  and  not 
infrequently  the  penis,  scrotum,  and  feet  are  oedematous. 

Among  the  220  rashes  recorded  by  the  Clinical  Society  of  London, 
161  were  erythematous,  37  were  urticarial,  17  were  mixed,  and  5  were 
petechial;  2  of  the  5  petechial  cases  died.    Of  33  rashes  noted  by  Moizard, 


PI. ATI:    LX. 


An  Unusual  Antitoxin  Eruption  exhibiting  Erythematous  Patches 
on  the  Trunk  and  Vesicular  Lesions  on  the  Face. 


PLATR    I.XI, 


The  Saine  Patient  as  Plate  LX. ,  showing  the  Vesicular 
Character  of  the  Lesions  on  the  Face. 


THE  SI'JIiUM  TREATMENT  OF  hi I'llTII l-llll A  757 

14  were  urticarial,  0  .sciirlaliiiiforin  cin l,liciii;i,  !)  polymorplioiis  erythema, 
and  1  purpura. 

DiS'i'iuiuri'ioN.  'Ilic  (lisli-ihiilioii  of  tlic  <iiipfi<»ii  is  cxtrciiifly 
irregular.  It  may  occur  U|)ou  any  j)()rti(>ii  of  the  culaiieous  surfaee. 
It  is  noted  with  particular  frequency  about  the  arms,  lej^s,  and  huttock.s, 
although  the  trunk  is  scarcely  less  commonly  atta(;ked.  The  face  often 
escapes,  but  by  no  means  always. 

The  most  frecjuent  region  for  the  ajjpearance  of  the  rash  is  the  site 
of  the  injection.  It  is  quite  common  for  an  erythematous  or  nrtiearial 
eruption  to  appear  about  the  cutaneous  puncture  and  the  surrounding 
skin  within  twenty-four  hours  after  the  injection;  this  frequently  dis- 
appears only  to  return  some  days  later  as  the  herald  of  the  general 
eruption.  Among  the  220  antitoxin  rashes  recorded  by  the  C'linieal 
Society  of  London,  40  were  first  seen  at  the  site  of  the  injecticMi. 

The  eruption  may  consist  of  but  a  few  scattered  patches,  or  it  may 
be  so  profuse  as  to  involve  the  greater  part  of  the  cutaneous  surface. 

The  eruption  ordinarily  persists  for  about  forty-eight  hours,  although 
in  some  cases  it  may  last  three,  four,  or  five  days.  The  purpuric  rashes 
continue  much  longer.  Occasionally  the  rash  will  begin  to  fade  and 
almost  disappear,  and  then  in  twenty-four  or  forty-eight  hours  reappear. 

Recurrent  Rashes. — The  eruption  following  the  use  of  diplitlieria 
antitoxin  is  occasionally  subject  to  recurrence.  The  rash  may  disappear 
and  return  in  a  few  days  or  several  weeks  afterward.  Among  134 
rashes  observed  by  us  within  a  year  and  a  half,  there  were  14  recurrent 
rashes.  The  earliest  relapse  occurred  three  days  after  the  first  eruption 
and  the  latest  seventeen  days.  There  is  sometimes  more  than  one  re- 
currence. The  GHnical  Society  of  London  reports  11  recurrent  rashes 
among  220  eruptions  collected.  The  following  table  gives  the  day  of 
appearance  and  of  recurrence  of  the  cases  observed  by  us: 

Eecurrent  Antitoxin  Eruptions. 

Primary  rash  appeared  in  : 

1  case  7  days  after  serum  injection,  and  again   3  days  later. 

"  "  "  "        "        5  "        " 

"  "  "  ■'        "      ]"  " 

"  "  •'         "         4  " 

"      14  " 

4  .. 


'      7 

'       4 

'      7 

'      6 

'     10 

'■'      6 

"      8 

'      8 

'      8 

'      6 

'     10 

'       6 

'      6 

Total    14 

Constitutional  Symptoms. — Antitoxin  rashes  are  commonly  accom- 
panied by  constitutional  disturbance  of  a  more  or  less  pronounced 
character.     In  the  majority  of  cases  there  is  elevation  of  temperature 


758  DIPHTHERIA 

with  its  usual  concomitant  symptoms.  The  pyrexia  is  extremely  variable ; 
in  some  cases  there  may  be  hyperpyrexia. 

We  have  occasionally  observed  temperatures  in  children  of  104°  and 
105°  F.  More  commonly  the  fever  does  not  rise  above  101°  or  102°  F. 
In  the  220  rashes  reported  by  the  Chnical  Society  of  London,  fever 
accompanied  the  eruption  in  136  of  them. 

The  fever  lasts  ordinarily  from  twenty-four  to  seventy-two  hours, 
although  it  may  persist  longer.  It  declines,  as  a  rule,  with  the  subsidence 
of  the  rash.  Headache  is  commonly  associated  with  the  fever  and  a 
variable  amount  of  prostration  is  present.  In  some  cases  the  prostration 
is  quite  pronounced. 

Vomiting  occurs  occasionally  in  children,  and  now  and  then  there  is 
diarrhoea.  Where  the  temperature  is  high  delirium  is  said  to  occur 
(Sevestre  and  Martin).  We  have  not  observed  delirium  in  any  of 
our  cases. 

A  very  commou  symptom  accompanying  the  antitoxin  rash  is  pain 
in  the  joints;  adults  often  bitterly  complain  of  this  arthralgia.  Articular 
swelling  is  noted  in  a  certain  proportion  of  cases.  The  wrists,  elbows, 
shoulders,  knees,  and  ankles  are  the  joints  most  commonly  attacked. 
The  swelling  usually  subsides  in  a  few  days. 

The  Clinical  Society  of  London  reports  arthropathies  40  times  among 
663  cases  of  diphtheria;  in  35  of  these  cases  the  joint  symptoms  accom- 
panied the  antitoxin  eruption. 

Causation  of  the  Serum  Phenomena. — The  phenomena  which  develop 
in  a  certain  proportion  of  cases  after  the  administration  of  antidiph- 
theritic  serum  are  without  doubt  dependent  upon  something  which  is 
contained  in  the  injected  fluid.  Inhere  is  strong  reason  to  believe  that 
the  antitoxic  principle  itself  has  little  or  nothing  to  do  with  the  eruption 
and  other  manifestations  produced.  It  has  been  quite  conclusively 
proven  that  plain  horse  serum  when  injected  into  individuals  will 
produce  eruptions  of  the  character  described  in  about  the  same  pro- 
portion of  persons  as  the  diphtheria  antitoxic  serum. 

The  serum  of  non-immunized  horses  was  injected  by  Bertin  into  a 
number  of  children  suffering  from  diphtheria  with  the  development  of 
rashes  in  a  considerable  proportion  of  them.  Four  children  suffering 
from  an  ordinary  sore  throat  were  injected  by  Sevestre  with  serum  of 
non-immunized  horses,  with  the  production  of  an  erythema  in  each  one. 

Johannsen,^  of  Christiania,  administered  hypodermically  2  to  15  c.c.  of 
pure  blood  serum  from  a  healthy  non-immunized  horse  to  23  persons  free 
of  diphtheria.  The  serum  given  to  19  of  the  individuals  was  filtered; 
4  received  unfiltered  serum.  A  more  or  less  generalized  erythema 
developed  in  12  of  the  23  patients  in  from  one  to  eleven  days.  The 
filtered  serum  produced  less  disturbance  than  the  unfiltered. 

It  has  long  been  known  that  the  injection  into  an  animal  of  an  alien 
or  heterogeneous  blood  serum — i.  e.,  a  serum  derived  from  an  animal 
of  another  species — is  followed  by  toxic  symptoms. 

1  Johannsen,  Bertin,  and  Sevestre.    Cited  by  Berg,  loc.  eit. 


THE  SI'IRUM  TRKATMl<:Nr  Oh'  Dl I'llTII FJUA  759 

Rumno^  believes  that  the  toxic  vi^i^x-i  of  blood  serum  depends  upon 
tli(;  aetioii  of  sj)eciiil  toxalbninins.  Alexander  Selinii(P  is  of  the  opinion 
that  the  toxie  elVeet  is  (hie  to  the;  action  of  the  sohibh'  fibrin  ferment 
of  OIK!  l)lood  sennn  u])on  the  second  ;mini;i,l. 

If  Ehrlich's  side-chain  theory  stands  the  test  (A  time  it  will  pnjbably 
be  found  that  the  serum  injected  contains  a  substance  which  acts  as 
an  intermediary  body. 

Herg,  aft(M-  using  antitoxic  serum  filtered  tliroiigh  a  T'liamberland 
filter,  and  comparing  th(>  results  with  unfiltered  sennn,  ef)nchided  that 
filtered  antitoxin  is  less  likely  to  give  rise  to  rashes.  Park,  of  New  York, 
is  not  convinced  that  this  is  actually  so. 

The  wide  variability  in  the  production  of  serum  rashes  Is  doubtless 
due  to  two  factors:  1.  Individual  susceptibihty  or  predisposition,  and, 
2,  peculiarities  in  the  blood  serum  of  certain  horses.  There  can  be  no 
question  that  the  serum  of  some  horses  gives  rise  to  a  larger  percentage 
of  antitoxin  rashes  than  that  of  others. 

Where  the  serum  of  an  animal  produces  an  unusually  large  num- 
ber of  eruptions,  that  animal  had  better  be  given  up  as  a  source  of 
antitoxin. 

Diagnosis  of  Serum  Rashes. — It  is  often  a  matter  of  difficulty  to  dis- 
tinguish between  an  antitoxin  eruption  and  the  eruption  of  measles 
or  scarlet  fever,  more  particularly  the  latter.  Secondary  infection  with 
scarlet-fever  poison  during  the  course  of  diphtheria  is  not  an  uncommon 
occurrence.  When  a  scarlatiniform  rash  develops  in  a  patient  who  has 
been  given  antidiphtheritic  serum,  the  question  arises.  Is  the  rash  the 
result  of  the  serum,  or  is  it  an  expression  of  scarlet  fever? 

No  more  difficult  problem  in  differential  diagnosis  arises  than  in 
these  cases.  The  diagnosis  may  be  easy  when  the  scarlet-fever  SMiiptoms 
are  complete  and  well  marked.  When  there  is  vomiting,  rapid  rise  of 
temperature,  an  aggravation  of  the  existing  angina,  a  characteristic 
tongue,  and  an  intense,  diffuse,  punctated  rash,  the  nature  of  the  phe- 
nomena may  be  readily  divined.  But  when,  as  so  often  happens,  there 
is  moderate  pyrexia  (100°  or  101°  F.),  and  a  diffuse  rash  of  moderate 
intensity,  the  solution  of  the  diagnostic  problem  is  at  times  impossible. 
The  difficulties  are  increased 'by  reason  of  the  fact  that  diphtheria 
patients  suffer  from  an  angina  and  from  glandular  enlargement,  and 
the  antitoxic  serum  may  produce  fever,  a  scarlatinoid  rash,  vomiting, 
and  prostration. 

In  our  experience  at  the  Municipal  Hospital,  scarlatinoid  eruptions 
have  formed  but  a  very  small  percentage  of  the  serum  rashes.  We 
have  observed  from  time  to  time  a  large  number  of  scarlatinoid  rashes 
accompanied  by  more  or  less  fever  in  the  diphtheria  wards,  but  we 
have  regarded  such  cases  as  scarlet  fever  and  have  sent  them  to  the 
"mixed  ward"  w^here  cases  of  double  infection  with  diphtheria  and 
scarlet  fever  are  treated.  Although  these  wards  always  contain  some 
well-pronounced  cases  of  scarlet  fever,  the  patients  sent  from  the  diph- 

'  Quoted  by  Berg,  loc.  cit.       ,  -  Ibid. 


760  '  DIPHTHERIA 

theria  wards  with  the  scarlatinal  rashes  have  rarely  contracted  scarlet 
fever.  This  experience  has  seemed  to  us  to  afl'ord  confirmatory,  though 
we  admit  not  conclusive,  evidence  that  the  diagnosis  was  correct. 

In  the  city  of  New  York  scarlatiniform  rashes  after  the  injection  of 
antitoxic  serum  seem  to  have  been  more  common  than  in  Philadel- 
phia, and  within  recent  months,  during  which  time  there  has  been 
used,  at  the  Philadelphia  Municipal  Hospital,  the  New  York  Board  of 
Health  serum,  it  has  appeared  to  us  that  scarlatinoid  rashes  from  the 
serum  have  been  more  frequent. 

The  features  Vvhich  tend  to  indicate  that  the  rash  is  of  serum  origin 
and  not  the  exanthem  of  scarlet  fever  are:  its  development  at  about 
the  proper  time  after  the  injection,  the  moderate  grade  of  the  accom- 
panying fever,  the  presence  of  severe  itching,  the  absence  of  a  recurrent 
angina  and  the  scarlatinal  tongue,  the  occurrence  of  joint  pains  or 
swellings,  irregularity  in  the  development  or  distribution  of  the  rash, 
the  brevity  of  its  duration,  and  the  absence  of  consecutive  desquamation. 

It  must  be  remembered,  however,  that  all  of  these  phenomena  have 
but  a  relative  value  in  the  diagnosis  and  that  in  many  cases,  after  due 
weighing  of  all  the  symptoms,  the  diagnosis  remains  obscure.  Other 
observers  of  experience  have  recognized  similar  difficulties  in  diagnosis. 


CH  A  PTER    X  V. 

i)isiNFi<x;'ri()x. 

Disinfection  of  Rooms. — Tlie  best  method  of  njoin  (Ji.sii)i'ecti(jii  known 
to  us  at  the  present  time  is  the  use  of  formaldehyde  gas  or  sulphur 
dioxide.  It  must  bt^  remembered,  however,  that  these  j^aseous  sub- 
stances accomplish  largely  a  surface  disinfection  and  cannot  be  depended 
upon  to  penetrate  to  any  considerable  degree  such  articles  as  mattresses, 
upholstered  furniture,  etc. 

In  view  of  certain  disadvantages  of  sulphur  fumigation,  to  which 
reference  will  be  made  later,  formaldehyde  gas  is  recognized  at  the 
present  day  as  the  most  useful  and  suitable  gaseous  disinfectant. 

The  advantages  of  formaldehyde  are  due  to  its  active  germicidal 
properties,  to  its  non-toxic  effects  upon  the  higher  forms  of  animal 
life,  and  to  the  fact  that  it  does  not  injuriously  affect  fabrics,  metals, 
etc.  It  appears  to  exert  no  detrimental  influence  whatever  upon  silks, 
woollens,  cotton,  linen,  tapestries,  carpets,  or  oil  paintings.  It  is  the 
only  efficient  disinfectant  that  can  be  employed  in  a  furnished  apart- 
ment without  any  destructive  influence  upon  the  contained  objects. 

The  germicidal  value  of  formaldehyde  is  doubtless  due  to  its  property 
of  combining  with  the  nitrogenous  organic  matter  wnth  which  it  comes 
in  contact.  It  destroys  bacteria  by  uniting  with  the  albuminoids  which 
make  up  the  protoplasm  of  these  micro-organisms.  It  likewise  acts 
as  a  deodorant  by  combining  with  the  nitrogenous  products  of  decaying 
animal  matter  and  forming  new  chemical  compounds. 

Formaldehyde  in  concentrated  volume  rapidly  kills  the  ordinary 
bacteria;  if  the  amount  of  gas  be  sufficient  and  the  exposure  prolonged, 
most  all  of  the  disease-producing  spores  are  also  destroyed. 

Despite  its  strong  germicidal  action,  formaldehyde  is  not  poisonous 
to  the  higher  forms  of  life.  Roaches,  bed-bugs,  vermin,  and  such 
animals  as  rats,  guinea-pigs,  and  rabbits  are  not  killed  by  moderately 
long  exposures.  An  intense  irritation  of  the  mucous  membranes  is, 
however,  produced,  which  may  terminate  fatally. 

Mosquitoes  directly  exposed  to  a  concentrated  volume  of  the  gas 
will  succumb,  but  formaldehyde  is  inferior  to  sulphur  fumigation  for 
the  destruction  of  these  insects. 

Formaldehyde  is  sold  in  commerce  in  40  per  cent,  solution  under  the 
name  of  formalin.  In  cold  weather  a  deterioration  in  the  strength  may 
occur  as  a  result  of  the  precipitation  of  some  of  the  insoluble  allied 
products. 

Preparation  of  the  Room  for  Disinfection. — Inasmuch  as  the 
gas  is  readily  lost  by  leakage  it  is  necessary  to  seal  all  the  cracks  and 


762  DISINFECTION 

crevices  through  which  an  escape  might  take  place.  Windows  should 
be  tightly  closed,  and  all  crevices  about  them  and  around  the  doors 
sealed  with  cotton-batting,  or,  better,  with  strips  of  gummed  paper. 
Keyholes  should  be  plugged  and  registers  and  flues  tightly  closed. 
An  open  fireplace  must  be  carefully  sealed.  After  the  room  is  made 
as  air-tight  as  possible  the  various  infected  objects  are  to  be  spread 
out  so  that  their  surfaces  are  fully  exposed  to  the  gas.  Wash-lines 
may  be  strung  across  the  room,  upon  which  should  be  suspended  bed- 
linen,  clothing,  towels,  etc.  Closets,  bureau-drawers,  and  all  similarly 
enclosed  spaces  should  be  opened  so  as  to  be  freely  permeated  by  the 
disinfectant. 

The  amount  of  gas  to  be  employed  and  the  duration  of  the  exposure 
will  depend,  to  a  certain  extent,  upon  the  method  used. 

Rooms  are  ordinarily  disinfected  by  formaldehyde  by  one  of  several 
methods.  The  gas  may  be  generated  from  its  watery  solution  by 
distilling  it  in  a  retort.  Formalin  is  used  for  this  purpose;  it  is  advised 
that  1  per  cent,  of  glycerin  be  added  to  raise  the  boiling  point  and 
lessen  the  polymerization  of  the  formaldehyde. 

Ten  ounces  of  formalin  should  be  used  for  every  1000  cubic  feet  of 
air  space. 

The  room  should  be  kept  closed  for  at  least  six  hours  and  preferably 
longer. 

Another  method  which  is  much  employed  is  the  production  of  the 
gas  from  a  formaldehyde  generator  or  lamp  by  the  dehydrogenation  of 
methyl  or  wood  alcohol,  mixed  with  water,  over  incandescent  platinum 
in  a  finely  divided  state  on  asbestos  disks. 

The  chief  advantage  claimed  for  this  method  lies  in  the  fact  that 
nascent  formaldehyde  is  liberated  and  that  the  gas  is  more  active  in 
this  state.  There  is  less  conversion  of  the  gas  to  paraform  and  a  less 
persistent  clinging  of  the  odor  in  the  room. 

Spraying  is  a  very  convenient  method  of  disinfection,  but  nmst  be 
employed  with  thoroughness  in  order  to  be  efficient. 

The  plan  at  present  employed  by  the  Philadelphia  Board  of  Health 
is  to  spray  all  surfaces  of  the  room  to  be  disinfected  with  a  mixture 
of  equal  parts  of  water  and  a  saturated  solution  of  formaldehyde  gas  in 
water  (formalin).  Three  pints  of  this  mixture  are  used  for  each  1000 
cubic  feet  of  air  space  in  the  room.  From  special  laboratory  investi- 
gations carried  out  by  the  Board  of  Health,  better  results  were  obtained 
from  the  employment  of  strong  solutions  of  formaldehyde  in  the  form 
of  a  fine  spray  than  from  any  other  method.  By  this  means  100  per 
cent,  of  the  test  objects  placed  in  the  room  were  killed. 

It  was  also  found  that  formaldehyde,  applied  in  this  manner  to 
bedding,  had  much  more  penetrating  power  than  when  applied  as  a 
gas. 

"  Of  900  beds,  including  mattresses,  covers,  and  pillows  of  different 
qualities,  that  were  thoroughly  sprayed  on  all  surfaces  in  this  manner, 
all  were  completely  disinfected,  as  demonstrated  by  the  death  of  test 
objects  placed  in  different  parts  of  the  bedding.     This  result  has  led 


DISINFECTION  ie,?j 

to  the  abaiuloniiicnt  in  most,  c'lscs  of  tlu-  rornifr  praoticc  of  removing 
beddiiijn^  IVom  tlio  si(;k-rooin  lor  (lisinlcclion  Wy  steam."' 

The  formalin  (5!)  jxm*  cent.  (Jihitionj  is  riipidly  sprayod  over  the  walls, 
flo:)rs,  and  ceiling  undcT  pressnrc  of  compressed  air.  A  long  elbow  gas- 
pipe  is  used  to  reach  the  ceilings  and  upper  portions  of  tlu;  walls. 

The  method  employed  by  the  Chicago  Tioard  of  Health  is  as 
follows:  Sheets  are  strung  diagonally  across  the  room  upon  wash- 
lines.  Formalin  is  then  sprayed  upon  the  sheets  by  a  specially 
devised  sprinkler.  The  spraying  must  be  done  quickly  on  account  of 
the  irritating  properties  of  the  gas,  and  yet  care  must  be  used  to 
apply  the  formalin  in  small  drops  and  not  in  large  splashes,  so  as  to 
secure  the  maximum  surface  for  evaporation  and  the  freest  evolution 
of  the  gas. 

.For  each  1000  cubic  feet  of  air  space  no  less  than  ten  ounces  of  formalin 
should  be  used.  It  is  advisable  for  the  disinfector  to  wear  rubber  gloves 
to  protect  the  hands  from  the  spray. 

The  room  is  kept  tightly  sealed  for  twenty-four  hoiu's,  after  which  it 
is   thoroughly  aired  and  sunned. 

In  the  use  of  any  of  the  formaldehyde  fumigation  methods  it  is 
highly  advantageous  to  use  spraying  as  a  supplemmfary  measure.  The 
formalin  in  half-strength  may  be  sprayed  upon  the  floors,  in  the  closets 
and  corners,  and  upon  bedding,  furniture,  etc. 

Another  method  of  formaldehyde  disinfection  is  by  heating  paraform, 
which  is  one  of  the  polymeric  forms  of  formaldehyde.  This  is  a  white 
powder  which  may  be  compressed  into  tablets  or  pastils.  These  are 
heated  in  small  lamps  and  the  gas  driven  off.  Tj  is  method  is  useful 
in  the  disinfection  of  small,  tightly  sealed  places  of  less  than  1000  cubic 
feet,  such  as  closets. 

For  each  1000  cubic  feet  no  less  than  two  ounces  of  paraform  should 
be  used. 

Sulphur  Dioxide. — ^The  gas  evolved  by  burning  sulphur  is  an 
excellent  surface  disinfectant,  but  has  certain  serious  disadvantages. 
Its  injurious  influence  upon  cottons  and  linen  fabrics,  and  especially 
upon  the  coloring  matter  in  various  articles,  unfits  it  for  use  in  furnished 
apartments. 

Sulphur  dioxide  has  a  destructive  effect  not  only  upon  bacteria,  but 
also  upon  animal  life.  It  may,  therefore,  be  advantageously  employed 
whenever  it  is  desired  to  kill  rats,  roaches,  fleas,  mosquitoes,  vermin, 
etc.  It  may  also  be  used  in  unfurnished  apartments  when  formaldehyde 
is  not  available.  It  has  the  further  advantage  of  being  cheap  and 
readily  procurable. 

For  a  room  of  1000  cubic  feet  of  air  space,  five  pounds  of  sulphur 
should  be  burned.  A  considerable  amount  of  moisture  must  be  present 
to  convert  the  sulphur  dioxide  into  sulphurous  acid.  The  method 
usually  employed  is  as  follows: 

The  room  is  prepared  as  for  formaldehyde  fumigation.  The  sulphur, 
in  the  form  of  flowers  of  sulphur,  is  placed  in  an  iron  pot  or  pan  and 

1  From  the  Bulletin  of  the  Bureau  of  Health,  Philadelphia.  Decembers,  1904. 


764  DISINFECTION 

this  is  set  in  a  tub  of  water.  The  water  surrounding  the  pot  lessens 
the  danger  of  fire  and  at  the  same  time  furnishes  the  necessary  moisture. 
The  sulphur  may  be  ignited  by  means  of  hot  coals  or  by  lighting  alcohol 
which  has  been  poured  into  a  concavity  in  the  sulphur. 

In  large  apartments  a  number  of  sulphur  pots  had  better  be  used. 
To  destroy  animal  life  the  fumigation  should  continue  for  two  hours; 
but  the  destruction  of  micro-organisms  requires  an  exposure  of  from 
sixteen  to  twenty-four  hours. 

Disinfection  of  Various  Articles.  Bedding. — The  gaseous  dis- 
infectants cannot  be  relied  upon  to  disinfect  mattresses  that  are  deeply 
infected.  These  should  be  subjected  to  steam  under  pressure.  Most 
large  cities  have  established  steam  disinfecting  plants  for  this  purpose. 
Where  the  facilities  are  not  present  for  thorough  disinfection  of  mattresses 
and  the  like  these  articles  had  better  be  destroyed  by  fire. 

Bedsteads  and  other  wooden  and  metallic  furniture  may  be  washed 
with  a  5  per  cent,  solution  of  carbolic  acid  or  the  same  strength  of 
formalin. 

Carpets  and  Rugs. — Carpets  and  rugs  should  be  exposed  to  the 
gaseous  disinfectants  and  in  addition  thoroughly  sprayed  with  a  5  per 
cent,  solution  of  formalin.  Where  the  carpet  or  rug  has  been  deeply 
soiled  by  infectious  discharges  it  is  best  to  have  the  same  subjected  to 
steam  disinfection  after  the  fumigation  of  the  room  is  performed. 

Books. — Unbound  books  should  be  subjected  to  steam  disinfection. 
Bound  books  may  be  thoroughly  disinfected  in  a  specially  devised, 
small,  air-tight  formaldehyde  chamber  in  which  a  partial  vacuum  may 
be  produced.  In  households  where  no  special  apparatus  is  at  hand 
a  few  drops  of  formalin  should  be  discreetly  sprinkled  upon  every 
page  of  the  book.  The  volume  with  its  pages  open  should  then  be 
placed  in  an  air-tight  box,  chest,  or  drawer,  and  an  excess  of  formalin 
placed  therein.  The  exposure  should  continue  for  not  less  than  twenty- 
four  hours  and  the  room  should  be  kept  warm. 

Letters  and  Money. — Letters  may  be  readily  disinfected  by 
clipping  away  a  corner  of  the  envelope,  dropping  in  with  an  eye-pipette 
a  few  drops  of  formahn,  and  placing  the  same  with  an  excess  of  formalin 
in  a  tight  box  for  six  hours  in  a  warm  room.  Dry  heat  or  steam  are 
surer  disinfectants,  but  often  are  not  available.  Paper  money  may  be 
sprayed  with  formalin  and  then  subjected  to  the  same  treatment  as 
letters.  Metal  money  can  be  boiled,  or  cleansed  in  a  5  per  cent,  carbolic 
acid  solution. 

Cadavers. — ^The  bodies  of  patients  who  have  succumbed  to  infectious 
diseases  should  be  thoroughly  enveloped  in  a  sheet  immersed  in  a 
5  per  cent,  solution  of  carbolic  acid,  or  a  1 :  1000  solution  of  corrosive 
sublimate.  The  sheet  is  nicely  adjusted  to  the  body  and  held  together 
by  pins. 

The  best  disposition  of  such  cadavers  is  by  cremation.  Where  this 
cannot  be  carried  out,  the  body  should  be  surrounded  with  twice  its 
weight  of  freshly  burned  lime  in  a  tight  coffin  and  interred  at  least  six 
feet  beneath  the  soil. 


f)isfNFi'JC'rioN  7(>r, 

Embalming  with  strong  solutions  of  foniialin  or  arsenic  destroys  all 
but  the  surface  infection,  and  this  may  f)e  treated  with  solutions  of 
carbolic  acid,  (;orrosive  snblimate,  or  formalin. 

Vehicles.- -Airdjulances,  carringcs,  street  ears,  and  th(;  like,  an;  best 
disinfected  by  running  tiiem  into  a  tightly  closed  ec^mpartirutnt  which 
may  be  quickly  filled  with  large  quantities  of  strong  formaldehyde  gas. 
In  a  specially  built  structin-e  of  this  kind  satisfactory  disinfection  may 
be  effected  in  an  hour.  Vehicles  which  can  b(;  tightly  clf)sed  may  be 
thoroughly  sprayed  with  a  5  to  U)  per  cent,  solution  of  fonnalin  and  the 
vapor  allowed  to  act  for  about  six  hours.* 

*  In  preparing  the  above  article  tiie  writers  have  consulted  the  excellent  book  on  "  Disinfection 
and  Disinfectants,"  by  Dr.  M.  J.  Rosenau,  Director  of  the  Uygienic  Laboratory  and  Passed  Assisiant 
Surgeon  U.  S.  Public  Health  and  Marine  Hospital  Service. 


INDEX. 


Ar>l)()MINAL  coiiiplicaXions  in  siiuili- 
pox,  287 
Abortion  in  smallpox,  21G 
Abscesses  in  smallpox,  229 
Accidental  cowpox  in  man,   142 
Actinomyces  in  va(!cine  virus,  103 
Adult  chickenpox,  327 
scarlet  fever,  347 
Aerial  transmission  of  scarlet  fever  con- 
tagium,  357 
of  smallpox  infection,   161 
Age  incidence  in  smallpox,  112 

in  measles  prognosis,  530 
Air  transmission  of  smallpox  infection, 

161 
Albuminuria  in  smallpox,  226 
Alopecia  after  smallpox,  191 
Altitude,   influence  of,  on  scarlet  fever, 

352 
America,  introduction  of  smallpox  into, 
147 
of  A'accination  into,   25 
Angina  scarlatinosa,  390 
Anginose  scarlet  fever,  382 
Animal  transmitted  virus,  97 
vaccination,  93 

advantages  of,  94 
in  America,  93 
Anomalous  measles,  497 
Antipyrin  eruptions  and  measles,   diag- 
nosis of,  527 
Antistreptococcus  serum  in  scarlet  fever, 

474 
Antitoxin  of  diphtheria,  action  of,  731 
curative  power  of,  738 
effect  of,  on  local  process,  735 
limitations  of,  736 
prophylactic  power  of,  737 
eruptions  and  measles,  diagnosis  of, 

529 
preparation  of,  732 
prophylactic  influence  of,  in  Munici- 
pal Hospital,  738 
treatment  of  diphtheria,  730 
unit,  732 
An ti vaccination  arguments,  114,  115,  119 
Apepox,  143 

Atmospheric    conditions    and    smallpox, 
156 
transmission  of  smallpox  infection, 
161 
Attack  rate  of  smallpox,  120 


BACrElMOLOGICAI.      diagnosis     <>i 
(liplitheria,  077 
impurities  of  vaccinr-,  virus,  102 
Bacteriology  of  diphtheria,  612 
of  measles,  521 
of  scarlet  fever,  430 
of  smallpox,  256 
of  tvphus  fever,  572 
Baths  in  smallpox,  299 
lieaugency  lymph,  92 
Bed-sores  in  smallpox,  231 
Bills  of  mortality,  smallpox  deaths,   109 
Black  smallpox,  204 
Blattern,   145 

Blood  changes  in  chickenpox,  335 
in  diphtheria,  670 
in  scarlet  fever,  436 
in  smallpox,  253 
Boils  after  vaccination,  S3 

iu  smallpox,  229 
Bousquet's  lymph,  92 
Bovine  lymph,  31 

vaccination  in  America,   93 
Bullous   eruptions  after  vaccination,  SO 


CALF-TRANSMITTED  virus,  94,  97 
Calf  vaccination,   93 
Camel,  smallpox  in,   143 
Camp  measles,  499 
Carbuncles  in  smallpox,  230 
Casual  cowpox  in  man,  142 
Chauveau's  experiments  with  variolation, 

88 
Chemnitz  smallpox  statistics,  118 
Chester  smallpox  statistics,   113 
Chickenpox,  316 

in  adults,   327 

blood  in,  335 

complications  and  sequelte  of,  329 

diagnosis  of,  335 

disseminated  gangrene  in,  330 

eruptive  stage  of,  322 

er3'sipelas  complicating,   330 

etiology  of,  318 

history  of,  316 

incubation  period  of,  320 

nephritis  in,  332 

pathology  of,  334 

prodromal  erythema,  322 

prognosis  of,  339 

pyaemia  complicating,  330 


768 


INDEX 


Chickenpox,  scarring  after,  326 
second  attacks  of,  319 
and  smallpox  coincident,   333 
symptomatology  of,  321 
synovitis  and  arthritis  in,  330 
treatment  of,  339 
with  other  exanthematous  diseases, 
332 
Chloral  eruptions  and  measles,  diagnosis 

of,  528 
Clavelee,  135 
Climate,   influence   of,   on   scarlet   fever, 

349 
Cohasset  lymph,  93 

Coincident  chickenpox  and  smallpox,  333 
Comparative  mortality  rates  of  variola 

and  varioloid,  278 
Comparison  of  course  of  vaccinia  with 

different  virus,  96 
Complications  of  chickenpox,  329 
of  diphtheria,   640 
of  measles,  501 
of  rubella,  561 
of  scarlet  fever,  395 
of  smallpox,   229 
of  typhus  fever,   583 
of  vaccination,  58 
Compulsory  vaccination  law  in  Germany, 

123 
Confluent  measles,   494 
smallpox,  199 

superficial,  212 
Conjunctivitis  in  smallpox,  232 
Contagious   impetigo    complicating   vac- 
cination, 70 
period  of  measles,  484 
Contagiousness  of   desquamating  epithe- 
lium in  scarlet  fever,  357,  462 
Contraindication  for  vaccination,  32 
Copaiba     and     cubebs     eruptions      and 

measles,  diagnosis  of,  529 
Copeman  and  glycerinated  lymph,  98 
Corneal  ulcer  in  smallpox,  233 
Cowpox,  17 

in  cow,  142 
Crede's  ointment  in  scarlet  fever,  469 
Croup  and  diphtheria,  diagnosis  of,  674 

meinbranovis,   633 
Cutaneous  gangrene  in  smallpox,   194 
Cytoryctes  variola^,  264 

life  cycle  of,  265 
of  Guarnieri  in  vaccinia,  85 


DEATH  rate  of   smallpox  among  vac- 
cinated and  un vaccinated,   117 
Decline  of  smallpox  after  introduction  of 

vaccination,   107 
Decrustation  in  smallpox,  186 
Definition  of  chickenpox,  316 
of  diphtheria,  598 
of  measles,  476 
of  rubella,  547 
of  scarlet  fever,  341 
of  smallpox,   144 
of  typhus,  566 


Delayed  vaccination,  38 
Delirium  in  smallpox,  182 
ferox  in  smallpox,  182 
Derivation  of  word  smallpox,  144 

variola,  144 
Dermatitis  bullosa  after  vaccination,  80 
exfoliativa  in  smallpox,  196 
herpetiformis  after  vaccination,  80 
Desiccation  in  smallpox,  185 
Deterioration  of  humanized  virus,  95 
Dewsbury  smallpox  statistics,   118 
Desquamation,     contagiousness     of,     in 
smallpox,  482 
in  measles,  497 
in  rubella,  556 
in  scarlet  fever,  374 

duration  of,   376 
Diagnosis  of  chickenpox,  335 

and  impetigo  contagiosa,  338 
and  smallpox,  335 
of  diphtheria,  672 
of  measles,  523 
of  rubella,  562 
of  scarlet  fever,  447 
of  smallpox,  266 
and  acne,  272 
and  acute  gastritis,  268 
and  chickenpox,  269 
and  drug  eruptions,  272 
and  eczema,  274 
and  glanders,  274 
and  impetigo  contagiosa,  273 
and  la  grippe,  267 
and  measles,  268 
and  meningitis,  267 
and  roseola  vaccinosa,  272 
and  scarlet  fever,  269 
and  syphihs,  270 
and  typhoid  fever,  267 
and  typhus  fever,  267 
of  typhus  fever,  586 
Diet  and  stimulants  in  smallpox,  301 
Diphtheria,  598 

age  factor  in  prognosis  of,  679 

incidence,  611 
albuminuria,  362 

alleged  ill-effects  of  antitoxin,  753 
antitoxin  in,  action  of,  731 
alleged  ill-effects  of,  753 
curative  power  of,  738 
dosage,  733 
effect  of,  on  local  process,  735 

on  paralysis,  753 
eruptions,  754 

fever  with,  758 
morbilliform,  756 
recurrent,  757 
scarlatinoid,  756 
ill-effects  of,  753 
laryngeal  form,   741 
limitations  of,  736 
mode  of  administrating,   736 
preparation  of,  737 
prophylactic  power,  737 
rashes,  causation  of,  754 
date  of  appearance,  755 


I  NT)  MX 


7G0 


I  )i))liLli('ri!i,,  ;i,nl.il,()\in  niHlics,  (li,'i,fi;ii(i.si.s  of, 

fever  in,  758 
frequency  of,  754 
results  in,  743 

in  (Jhicjimo,  750 
iti  .lap.'ui,  74() 

in    l-lii'   Mutiiciiwil    Ho.spital 
in  I'liiludclplii.'i,  749,  752 
in  N(W  York  (.'il.y,  7  IS,  751 
in  Willanl  l';i.rk(',r  Il().si)itiii, 
New  York,  749,  751 
treatment  of,  730 
unit  732 
value  of,  743 
avirulent  diphtheria  bacilli,   616 
bacilli    of    biolofrical    characters    of, 
614 
in  blood  and  internal  orj^ans,  617 
distribution  of,  in  body,  617 
in  lungs,  663 
in  lymph  nodes,  668 
in  scarlet  fever  throats,  399 
in  throats  of  exposed   persons, 
619 
of  healthy  persons,  618 
persistence  in  the  throat,  618 
staining  properties  of,  613 
types  of,  613 
virulence  of,  616 
bacillus,  general  infection  with,  617 
growth  of,  on  bouillon,  615 
on  gelatin,  615 
on  glycerin  agar,  615 
on  Loeffler's   blood    serum, 

614 
in  milk,  615 
on  potatoes,  615 
Neisser's  stain  of,  614 
morphology  of,  613 
pathogenesis  of,  615 
bacteriological  diagnosis  of,  677 
bacteriology  of,  612 
blood  changes  in,  670 
in  Boston  City  Hospital,  mortality 
of    laryngeal    form, 
743 
results  of  antitoxin  in, 
747 
bronchopneumonia  in,  641 
at  autopsy,  661 
bacteriology  of,  662 
catarrhal  croup,  diagnosis  of,  674 
causation  of  serum  rashes,  758 
changes  in  adrenal  bodies,  670 
in  alimentary  cjuial,   664 
in  blood,  670 
in  heart  muscle,  660 
in  intestines,  665 
in  Iddneys,  667 
in  liver,  665 
in  lungs,  661 
in  lymph  nodes,  668 
in  nervous  s^'stem,  670 
in  panci'eas,  670 
in  pituitary  bod}^  670 


I  )iplil  liiii;i,    changes     in     pliiiml     ni'-ni- 
branes,  fi63 

in  salivary  gl;i,nd.s,  670 

in  skeletal  inuscles,  669 

in  Hpl(!en,  (i64 

in  testicles,  670 

in  thymus  gland,   669 

in  (liyroid  glund,  670 
in  (Miicago,  aniiloxiri  n-sults  in,  750 
(4iroiiic  stenosis  of  larynx  in,  726 
circulatory  symptoms,  631 
coni])licatirig  scarlet  fever,   397 
corn})lications  of  kidneys,  667 

of  lung,  641 

of  lymph  glands,  642 

ol'  scarlf^t  fever,  644 

Mild   sequela;  of,  540 
conjiuictival,  626 

constitutional  predisposition  to,  609 
course  of,  636 

cultures  of,  for  diagnosis,  677 
ciitaneous,  627 
definition  of,  598 
diagnosis  of,  672 

of  serum  rashes,  759 
dissemination  of  infection,  607 
duration  of,  636 

of  membrane  in  throat,  740 
ear  inA^olvement  in,  626 
endocarditis  in,  66 
epistaxis  in,  625 
eruptions  after  antitoxin,  754 
erythema  in,  627 
etiology  of,  602 

examination  of  cultures  of,  678 
exudate  in,  624 

location  of,  658 
of  e3^es,  626 
favorable  cases  of,  637 
fever  in,  630 

folUcular  tonsillitis,  diagnosis  of.  675 
gangrenous  pharj-ngitis,  diagnosis  of, 

676 
general  paralysis  in,  650 
geographical  distribution,   604 
heart  changes  in,   660 

failure  in,  641 
hemiplegia  in,   647 
hepatic  changes  in,  665 
herpetic    pharjTigitis,    diagnosis   of, 

675 
liistopathologv  of  membrane,  658 
histoiy  of,  598 

indications    for    operati^•e    interfer- 
ence, 715 
infection  in  milk,  608 
influence  of   domestic  environment, 
606 

of  race,  613 

of  rainfall,  605 

of  schools,  60S 

of  season,  605 

of  sex,  611 
isolation  of  well  persons  harboring 

baciUi  of,  619 
intubation  in,  711^ 


49 


770 


INDEX 


Diphtheria,  intubation  in,  prolonged,  725 
technique  of,  715 
in  Japan,  results  of  use  of  antitoxin, 

746 
kidney  changes,  667 

complications  of,  642 
laryngeal,  633 

antitoxin  in,  741 
operative  measures  in,  711 
leukocytosis  in,  671 
liver  changes,  665 
lobar  pneumonia,  642 
location  of  membrane,  658 
Loeffler's  solution  as  local  applica- 
tion, 693 
of  methylene  blue,  613 
lung  changes,  661 
making  of  cultures  of,  677 
malignant  type  of,  638 
measles  complicating,  645 
membrane  in  stomach,  664 
mercurial  applications  in,  692 
in    Metropolitan     Asylums'     Board 
Hospitals    of    London,    antitoxin 
results,  746 
middle-ear  involvement,  626 
mild  type  of,  636 

mortality  of  intubation  cases  in  Wil- 
lard  Parker  Hospital,  742 
in  Mvmicipal  Hospital,  743 
of  tracheotomized  cases,  742 
in   Municipal  Hospital  of   Philadel- 
phia,   antitoxin    results, 
749,  752 
mortality  of  intubation,  743 
myocardial  changes,  660 
myocarditis,  660 
nasal,  624 

irrigations  in,  697 
treatment  of,  697 
nephritis  in,  642,  667 
nervous  symptoms,  633 
in  New  York  City,  antitoxin  results 

in,  748,   751 
of  nose,  624 
nose-bleed,  625 
oedema  in,  628 

after  antitoxin,   756 
paralysis,  646 
general,  650 
incidence,  753 
of     cardiac    and    respiratory 

nerves,  649 
of  soft  palate,  649 
pathology  of,  658 
pericarditis  in,  660 
period  of  incubation  in,  620 
pleurisy  in  642 
prognosis,  678 

prognostic  significance  of  age,  679 
of  exudate,  682 
of  nasal  involvement,  683 
of  paralysis,  686 
of  pulse,  685 
of  race,  682 
of  renal  involvement,  686 


Diphtheria,    prognostic     significance    of 
sex,  681 
of  temperature,  684 
of  toxaemia,  684 
pulse  in,  631 
rash  in,  627 
rashes  of,  754 

after  antitoxin,   754 
recurrence  of,  640 
recurrent  attacks  of,  610 
in  Russian  Hospitals,  antitoxin  re- 
sults, 744 
septic  cases  of,  638 
variety  of,  629 
serum  rashes  in,  754 
severe  type,  636 
site  of  infection  in,  610 

of  skin,  627 
smear  preparation  for  diagnosis  of, 

677 
statistical  table  of  antitoxin  results 
in   Boston   City 
Hospital,  747 
in  Chicago,  750 
in  Metropolitan 
Asylums'  Board 
Hospitals,  746 
in  Municipal  Hos- 
pital    of     Phil- 
adelphia,    749, 
752 
in    Russian    Hos- 
pitals,  744 
in  St.  Petersburg, 

745 
in  Willard  Parker 
Hospital,       749 
752 
indicating  duration  of  mem- 
brane in  throat,  740 
of   date   of   appearance   of 

antitoxin  rashes,  755 
of  mortality  from  laryngeal 
form  in  Boston  City 
Hospital,  743 
from    laryngeal    form, 

742 
in  tracheotomy,  742 
of  intubation  in  Muni- 
cipal    Hospital, 
743 
in  Willard  Parker 
Hospital,  743 
of    recurrent    antitoxin 
rashes,  757 
of  stomach,  664 

St.  Petersburg  results  of  use  of  anti- 
toxin, 745 
stomatitis,  differential   diagnosis  of, 

676 
sj^mptomatology,  622 
syphilitic    sore    throat,    differential 

diagnosis  of,  676 
termination  of,  636 
throat  appearances   in,    622 
tincture  of  the  chloride  of  iron  in,  700 


IN/J/'JX 


771 


DipliUK^ri.'i,,  loxiciiiiji,  of,  628 
tmclH'()(,()my  ill,  727 

iiidiciitioriH  for,  71  I 
treatiiKMil,  of,  0X7 
nlcoliol  ill,  705 
iUi(.iH(\|)ti(t  .Mnijlic'itions  in,  (HM 

of  jLiinil,  ()iW 
biciiluridc  oT  incnMiry  in,  702 
(■;ilnmcl    in,    70;{ 

snMiin.'i.l  ion    in,    707 
(•;uisU(!  applic.'Uions   in,   000 
cliloratc,  of  potash  in,  (iOI 
oonstitiitioiijil,   700 
digitalis  in,  7or) 

ol'  clijilit.iicril  ic  con  jnncl  i\i- 
tis,  099 
emetics  in  ineinhnmoiis  croup, 

709 
extubation,  733 

technique  of,  723 
gargles  in,  value  ol',  091 
internal,  700 

indications  for,  700 
irrigation  in,  69(5 

with  saline  solution,  698 
intubation  in,  718 

dangers  and  difficulties  of, 

718 
feeding  after,  721 
prolonged,  725 
technique  of,  715 
lactic  acid  in,  695 
of  laryngeal  form,  708 
local,  690 

Lfiefller's  solutions  in,  693 
of  membranous  croup,  708 
mercury  in,   709 
steam  in,  709 
mercurial  applications  in,   692 
of  ocular,  699 

operative,  indications  for,  715 
measin-es  in  laryngeal  form, 
711 
of  paralysis,  707 
potassium  chlorate  in,  703 
preventive,  687 

removal  of  intubation  tube,  723 
serum,  730 
slaked  lime  in,  710 
sodium  benzoate  in,  705 
solvents  of  exudate,  694 
spraj's  in,  696 
strychnine  in,  705 
tincture  of  the  cliloride  of  iron 

in,  700 
turpentine  in,  704 
whiskey  in,  706 
ulcerations  from  pressure  of  intuba- 
tion tubes,  726 
urine  in,  632,  642 
in  ^^'illard  Parker  Hospital,  mortal- 
ity in  intubation,  742 
results     of     antitoxin, 
749,  751 
with  scarlet  fe\-er,  644 
with  measles,  645 


DiphthrTitic  [jaralyHis,   610 
Disinlcction,  761 

of  bcr|(lin(r,  761 

of  books,  761 

of  cadaverw,  764 

of  (:arj)ets,  764 

of  letters,  764 

of  money,  764 

prcp.'ir.'ition  of  room  for,  761 

in  sin.'illpox,  285 

by  spniying  with  loriiialin  w>liitinris, 
762 

with  paraforni  pastils,  763 

with  sulphur  dioxide,  763 

of  v(4iicl(;s,  765 
Dissenting  views  as  to  air  transmission  of 

smallpox  infection,   164 
Domestic  animals,  tran.«mission  of  small- 
pox inf(!ction   by,    165 

EAR  complications  in  smallpox,  235 
Eaux  aux  Jambes,  138 
Eczema  following  vaccination,  79 
Effect  of  glycerin  on  bacteria,  101 
Egyptian  plague,  145 
En  anthem  of  measles,  489 

of  scarlet  fever,  373 

of  smallpox,  180 
Equination,  140 
Equine  variola,  138 
Eruption  of  measles,  493 
Eruptive  stage  of  smallpox,  173 
Erysipelas  comphcating  smallpox,  230 

after  vaccination,  72 
Erythema  multiforme  complicating  vac- 
cinia, 70 

scarlatini forme  in  smallpox,  196 

scarlatinoides,  419 
Etiology  of  chickenpox,   318 

of  diphtheria,  602 

of  measles,  478 

of  rubella,  549 

of  scarlet  fever,  344 

of  smallpox,  150 

of  tA'phus  fever,  568 
Exceptionally  mild  smallpox,  206 
Exfoliative  dermatitis  in  smallpox,  196 
Extubation  in  diphtheria,  723 
Eye  complications  of  variola,  231 

FALSE  vaccination,  42,  49 
Favorable    s^•mptoms  in  smallpox. 
281  ■ 

FeA'er  in  measles,  489 
in  scarlet  fever,  366 
in  smallpox,  183 
First  vaccination  of  .Tenner,  91 
Foetus,  smallpox  in,  221 
Formalin,  761 
Formaldehyde  disinfection.  761 

effects  of.  on  vennin.  761 
French  and  German  Armv,  smallpox  sta- 
tistics. 121 
French  measles.     See  Rubella,  547 
Furunculosis  after  vaccination,  S3 


772 


INDEX 


GAIjBIATI  and  animal  vaccination,  93 
Gangrene,  in  scarlet  fever,  422 
in  vaccination,  67 
of  skin  in  smallpox,  194,  231 
Gangrenous  angina  in  scarlet  fever,  396 
Generalized  vaccinia,  60 
German    compulsory    vaccination    laws, 
123 
and   French   army   smallpox   statis- 
tics, 121 
German  measles.     See  Rubella,  547 

vaccination  commission,   123 
Germicidal  action  of  glycerin,   100 
value  of  glycerin  in  lymph,  98 
Glossitis  variolosa,   181 
Gloucester  smallpox  statistics,  118 
Glycerin,  effects  of,  on  bacteria,  101 

germicidal  action  of,  100 
Glycerinated  lymph,  97 

advantages  of,  101 
duration  of  activity  of,  105 
preparation  of,  103 
value  of,  98 
Goat  pox,  138 

Golden  rule  of  vaccination,  28,  31 
Grease,  138 
Guarnieri's  bodies,  263 

in  vaccine  lesions,  85 


HEART  complications  in  smallpox,  236 
Heifer  vaccination,  93 
Hemorrhagic  measles,  499 

scarlet  fever,  387 

smallpox,  202 

pathological  changes  in,  251 

typhus  fever,  585 

vaccinia,  63 

varioloid,  206 
History  of  chickenpox,  316 

of  dijjhtheria,  598 

of  measles,  476 

of  rubella,  547 

of  scarlet  fever,  341 

of  smallpox,  144 

of  typhus  fever,  566 
Histology  of  skin  in  smallpox,  242 

of  vaccine  lesions,  83 
Hornpox,  213 
Horsepox,  138 
Human  equination,  140 

ovination,   138 

smallpox  from  material  from  vario- 
lated cows,  89 
Humanized  virus,  30 

deterioration  of,  95 
Hygiene  of  vaccination,  30 


ILLNESS,  initial,  of  smallpox,  167 
Iodine  used  locally  in  smallpox,  311 
Impetigo    contagiosa   complicating   vac- 
cination, 70 
varicellosa,  325,  330 
variolosa,  192 


Immunity  of  vaccinated  physicians  and 

nurses  against  smallpox,  127 
Incubation  period  of  chickenpox,  320 
of  diphtheria,  620 
of  measles,  487 
of  rubella,  550 
of  scarlet  fever,  363 
of  smallpox,  166 
of  typhus,  575 
Infected  articles,  persistence  of  smallpox 

poison,  160 
Infection  of  smallpox,  157 

carried  in  garments,  160 
transmitted  in  the  air,  161 
Infectious  period  of  smallpox,  157 
Infectiousness  of  blood  in  smallpox,  255 
Infectivity,  period  of,  in  scarlet  fever,  355 
Initial  stage  of  smallpox,  167 
Inoculation,  148 

declared  illegal,  J 15 
with  ovine  lymph,   138 
practice  of,  in  England,  114 
of  smallpox  in  America,  25 
and  smallpox  prevalence,   114 
Inoculated  smallpox,  214 
Inoculability  of  measles,  478 
of  scarlatinal  virus,  354 
of  varicellous  fluid,  319 
Insanity  after  smallpox,  237 
after  typhus  fever,  584 
Insects,  transmission  of  smallpox  infec- 
tion by,  165 
Institution  epidemics  of  measles,  531 
Insusceptibility  to  smallpox,  150 

to  vaccination,  43 
Intrauterine  smallpox,  222 
Intubation  in  diphtheria,  711 

dangers  and  difficulties  of,  718 
instruments,  712 
prolonged,  725 

treatment  and  feeding  after,  721 
Invasive  stage  of  measles,  488 
Involution  of  eruption  in  smallpox,  185 
Iritis  in  smallpox,  235 
Irregularity  in  measles  eruption,  500 

in  scarlet  fever,  388 
Itching  in  smallpox,  189 
Isolation  in  scarlet  fever,  461 

of   smallpox   patients,    duration   of, 
287 


JAIL  fever.     See  Typhus,  566. 
Jefferson's  letter  to  Jenner,   133 
Jefferson,  Thomas,  and  vaccination,  28 
Jenner,  Edward,  17 

Jefferson's  letter  to,  133 
on  relation  of  cowpox  to  smallpox, 
90 
Jenner's  first  vaccination,  91 
Joint  disease  in  smallpox,  237 


KINEPOX,  17 
Kindpocken,  112 
Kilinarnock  smallpox  st^-tistics,   113 


INDEX 


773 


Klcihs-T/Ocmcr  h.-utilliis,  discovrTy  of,  502 
KopliU'.M  spol.s  in  incjislcs,  'lOl 

(liiif^iio.sMc  v.'iliK'  of,  r)2.'i 
Kiili|)i)ck('n,  17 


LA  I'ETITE  VEROI.E,   Ur, 
Lady   Montague    and    inoculalion, 
148 
Laryngeal  dipliihoria,  033 
Jioiwislcr   smallpox   statistirn,    IIK,    1 H), 

121 
Leprosy  after  vaccination,  70 
Leidvocytosis  in  scarlet  fever,    137 
Fjoeal  irealnient  of  sniall|)ox,  :i(J() 
Jjoelller's  solution  of  methylene  blue,  613 
Long  humanized  virus,  07 
Lord  Ma(^aulay  on  the  ravages  of  small- 
pox, 147 
Louis  XV.  attacks  of  smallpox,  152 
liupus  vulgaris  after  vaccination,  78 
Lymphatic  glands  in  scarlet  fever,  378 
Lymph,  glycerinated,  07 

advantages  of,  101 
natural  sources  of,  91 
preparation  of,  103 
Lyons    Commission    on    variolation    oi' 
cows,  88 


MACAULAY,  on  the  ravages  of  small- 
pox, 147 
Malignant  measles,  499 

scarlet  fever,  385 
Marseilles  smallpox  statistics,   118 
Martin's  lymph,  93 
Measles,  476 

in  adults,  482 
age  incidence,  481 
albuminuria  in,  512 
anomalous  cases  of,  497 
aphthous  stomatitis  in,  505 
bacteriology  of,  521 
blood  changes  in,  520 
bronchopneumonia  in,  503 
bullous  eruptions  in,  508 
camp,  499 

cancrum  oris  in,  512 
capillar}^  bronchitis,  503 
changes  in  blood  in,  520 

in  the  liver  in,  520 

in  lungs  in,  520 

in  lymphatic  glands  in,  520 

in  nmcous  membranes  in,  519 

in  skin  in,  518 

in  spleen  in,  520 
character  of  epidemic  and  prognosis 

of,  532 
chorea  after,  508 
climate  and  prognosis  of,  533 
complications  of,  501 

alunentary  tract,  505 

ear,  510 

eye,  509 

glandular,  512 

heart,  511 


Measles,  compliraf  ions  of,  kidney,  511 

laryngeal,  501 

lung,  502 

nervous,  506 

skin,  508 
confluent,  494 
contagious  period,  484 
deaf-mutism  and,  51 1 
desquamatif)n,  497 
drug  eniptions,  differential  diaiBfnoHiB 

of,  527 
diagnosis  of,  523 
diarrluea  in,  506 
disseminated  sclerosis  in,  507 
eczema  after,  509 
effect  of,  on  chronic  disea.sf^s,  519 

season  on,  483 
exanthem,  489 
endocarditis  in,  511 
epidemics  of,  482 

in  institutions,  531 
eruption  in,  493 

hemorrhagic,  499 

irregularity  of,  500 

presence  of  papules,  494 
of  vesicles,  494 
eruptive  period  of,  493 
erythema  nodosum  after,   509 
etiology  of,  478 
fever  in,  489 
gangrene  of  lungs  in,  505 

of  skin  in,  508 
gangrenous  stomatitis  in,  512 
hemorrhagic,  499 
herpes  facialis  in,  508 
history  of,  476 
incubation  period  of,  487 
influenza,    differential    diagnosis   of, 

525 
inoculabihty  of,  478 
insanity  after,  506 
isolation  of,   537 

utility  of,  538 
KopUk's  spots,  490 
lobar  pneumonia  in,  504 
malignant  form  of,  499 
membranous  laryngitis  in,  502 
meningitis  in,  508 
mental  disorders  in,  506 
mild  form  of,  497 

type  of,  498 
mode  of  contagion,  479 
morbilhform  erythemata,  differential 

diagnosis  of,  527 
noma  in,  512 
notification  of,  536 
paralysis  after.  507 
pathology  of,  518 
pericarditis  in,  511 
pigmentation  in,  496 
pleuris}-,  504 

post-rubeoUc  rashes  in,  501 
pre-eruptive  rashes.  492 
pregnant  women.  517 
pre\-ious  health  of  patient  and  prog- 
nosis of,  532 


774 


INDEX 


Measles,  prodromal  or  invasive  stage  of, 
488 
prognosis  of,  529 
prophylaxis  of,  535 
pulmonary  tuberculosis  after,  504 
purpura-  in,  512 
recession  of  rash,  501 
relapses  in,  486 

rubella,  differential  diagnosis  of,  524 
scarlet    fever,   differential   diagnosis 

of,  524 
season  and  prognosis  of,  533 
smallpox,  differential  diagnosis  of,  525 
susceptibility,  480 
symptomatology,  487 
favorable,  535 
unfavorable,  535 
syphilis,  differential  diagnosis  of,  527 
third  attacks,  486 
treatment  of  535 

of  bronchopneumonia  in,  544 
of  cancrum  oris  in,  543 
of  complications  in,  542 
of  conjunctivitis  in,  543 
of  itching  in,  542 
of  laryngitis  in,  543 
of  nose-bleed  in,  543 
of  otitis  in,  545 
temporary  immunity,  481 
tuberculosis  cutis  after,  509 
typhoid  form,   499 
typhus  fever,    differential    diagnosis 

of,  526 
ulcerative  stomatitis  in,   505 
urticaria  in,  508 
vulvitis  in,  512 
with  other  infections,  518 
without  catarrhal  symptoms,  497 
without  eruption,  498 
fever,  497 
Membranous  angina  in  scarlet  fever,  396 

croup,  633 
Mild  measles,  497 

type  of  smallpox,  206 
Miliary  vesicles  in  scarlet  fever,  370 
Milk,  scarlet  fever,  infection  in,  357 
Miscarriage  in  smallpox,  216 
Mitigated  smallpox,  209 
Modified  smallpox,  209 
Monkey,  smallpox  in,  143 
Montague,  Lady,  and  inoculation,  148 
Montreal  epidemic  of  smallpox,  159 
Morbid  anatomy  of  scarlet  fever,  439 
Morbilli   confluentes,  494.     See   measles, 
476 
hemorrhagic,  495 
Iseves,  494 
miliaris,  494 
papulosi,  494 
vesiculosi,  494 
Morphine  in  smallpox,  298 
Mortality  of  smallpox  in  the  prevaccina- 

tion  period,  275 
Mucous  membrane  eruption  in  smallpox, 

180 
Multiform  erythema  after  vaccination,  70 


NATURAL  cowpox  in  cow,  142 
Negri  and  animal  vaccination,  93 
Negroes,  smallpox  in,  154,  276 
Neisser's  stain  for  the  diphtheria  bacillus, 

614 
Nervous  complications  of  measles,  506 

in  smallpox,  237 
Noma  in  scarlet  fever,  422 


OCULAR  complications  of  variola,  231 
(Edema  of  glottis  in  smallpox,  181 
Orchitis  in  smallpox,  237 
Otitis  media  in  scarlet  fever,  400 

in  smallpox,  235 
Ovination,  137 
human,  138 


PALMAR  lesions  in  smallpox,  187 
Paraform  disinfection,  763 
Paralysis  in  smallpox,  238 
Paraplegia  in  smallpox,  239 
Passy  lymph,  92 
Pathology  of  chickenpox,  334 
of  diphtheria,  658 
of  measles,  518 
of  scarlet  fever,  436 
of  smallpox,  242 
of  typhus  fever,  573 
Pathological     changes     in     hemorrhagic 

smallpox,  251 
Pearson's  lymph,  91 
Pemphigus  after  vaccination,  80 
Period  of  incubation  of  chickenpox,  320 
of  diphtheria,  620 
of  measles,  487 
of  rubella,  550 
of  scarlet  fever,  363 
of  smallpox,  166 
of  typhus  fever,  575 
Petechial  fever.     See  Tj^phus,  566. 
Phimosis  in  smallpox,  237 
Phlebitis  after  smallpox,  237 
Pigmentation  after  measles,  495 

after  smallpox,  190 
Plantar  lesions  in  smallpox,  187 
Pleurisy  in  smallpox,  236 
Pneumonia  in  smallpox,  236 
Pock  diseases  of  lower  animals,  135 
Pocken,  145 

Postrubeolic  rashes,  501 
Postvaccinal  lupus  vulgaris,  78 
Postvariolous  rashes,  196 
Prague,  effect  of  introduction  of  vaccina- 
tion in,  107 
Precocious  vaccinia,  41 
Pre-eruptive  rashes  in  measles,  492 
Pregnancy,  influence  of,  in  scarlet  fever 

359 
Pregnant  women,  smallpox  in,  215 
Prevention  of  pitting  in  smallpox,  308 
Prodromal  erythema  in  chickenpox,  322 
rashes  in  smallpox,  171 
stage  of  smallpox,  167 


iNi)i<:x 


77r, 


l^r()f!;ru)His  ol'  cliiclu'ripox,  XV.) 

of  (li|)li(  licria,,  ()7X 

of  mcMslcs,  520 

(if  fiilicll.'i,,  r>(')\ 

of  sciiJ-lcl.  f(tvcr,  •If)? 

of  siii;i,lli)()X,  27r) 

of  I  yplms  f(!vcr,  589 
I'fopliyliixi.s  of  nitiiiIli)ox,  2<S2 
I'roi.o/.oii  in  .sc;irl<'t>  fc^vcr,    I'A'.i 

in  Viifiola  .'uid  vaccinia,  2(12 
l's(Mi(lo(li|)litJicr'ia,  ()r)2 

bacilli,  ()l!) 

coinnuinicabilily  <>f,   0.^;^ 

(liiiSnosis  of,  <)75 

Ij-calmcnl.  of,  (ir)7 
Psoudokcloidal   fj;rowths  after  sniaIli)ox, 

2:^0 
Psoriasis  after  vaccination,  82 
i'lKM'pcral  scarlet  fcvor,  359 
I'uerperium,  influence  of,  in  scarlet  fever, 

359 
Purpura  hemorrhagica  in  scarlet    fever. 
420 

variolosa,  203 
Pustular  hemorrhagic  variola,  205 
J'ya^mia  after  vaccination,  64 

in  smallpox,  241 


QUARANTINE  in  scarlet  fever,  461 
in  smallpox,  283 
Quinine  eruptions  and  measles,  diagnosis 
of,  528 

RACE,  influence  of,  on   scarlet   fever, 
353 
Raspberry  tongue   in   scarlet  fever,  374 
Recurrent  eruptions  in  scarlet  fever,  393 

smallpox,  151 
Red  light  treatment  of  smallpox,  304 
Relapse  in  rubella,  562 
Relation  of  horsepox  to  cowpox,  139 
Relationship  of  cowpox  to  smallpox,  87 

of  vaccinia  to  smallpox,  87 
Respiratory   complications  in   smallpox, 

236 
Retained  intubation  tubes,  726 
Retroequination,  142 
Retrogression   of   eruption   in   smallpox, 

185 
Retrovaccination,  51 
Revaccination,  45 

statistics  of,  120 
Rhazes'  description  of  smallpox,  145,  146 
Roseola  vaccinosa,  37,  68,   171 
Rotheln.     See  Rubella,  547 
Royalty,  smallpox  deaths  among,  149 
Rubella,  547 

age,  incidence  of,  550 

albuminuria  in,  561 

coincident  with  other  diseases,  562 

complications  and  sequela^  of,  561 

cough  in,  558 

definition  of,  547 

desquamation  in,  556 


HubcMa,  diagnosis  ol',  562 

diiratioii  of  isolation  in,  565 

of  rash,  555 
eruptions  of,  anomalous,  555 

character  of,  554 
(Miology  of,  549 
f(!ver  in,  557 
history  of,  557 
hoarseness  in,  558 
influenza,   dilfercntial    diagnosis    of, 

561 
it,cliiiig  in,  559 
lymphatic  glands,  559 
measles,  differential  diagnosis  of,  562 
nausea  and   vomiting  in,  559 
period  of  eruption  in,  552 
of  incubation  in,  550 
of  invasion  in,  551 
prognosis  of,  564 
pulse  and  respiration  in,  559 
relapses  in,  562 
second  attacks  of,  562 
scarlatinifonn  variety^  of  rash,  556 
scarlet  fever,  differential  diagnosis  of, 

564 
sneezing  in,  557 
sore  throat  in,  558 
symptomatology  of,  550 
synonyms  of,  547 
treatment  of,  565 
tongue  in,  558 
Rubeola.     See  Measles,  476 


SACCO'S  lymph,  92 
Sanitation  and  vaccination  in  Glas- 
gow, 116 
Scaling  in  scarlet  fever,  374 
Scarlatina.     See  Scarlet  fever,  321 
anginosa,  382 
faucium,  390 
hemorrhagica,  387 
maligna,  385 
miliaris,  370 
papulosa,  370 
pempliigoidea,  371 
simplex,  365 
sine  angina,  392 
eruptione,  390 
exanthemate,  390 
febre,  388 
with  desquamation,  392 
vesicularis,  370 
Scarlatinal  infection,  mode  of  reception, 
355 
rheumatism,  419 
virus,  inoculability  of,  354 
Scarlatinifonn  erythema,  449 

in  smallpox,  196 
Scarlet  fever,  341 

abscesses  in,  425 

of  brain  in.  403 
in  adults,  347 
afebrile  cases  of,  368 
age  influencing  prognosis,  45S 


776 


INDEX 


Scarlet  fever  amblyopia,  405 
anginose  form  of,  382 
antistreptococcus  serum  in,  474 
and  antitoxin  rashes,  451 
bacteriology  of,  430 
blebs  in,  424 
blood  in,  .436 
bronchial  catarrh  in,  381 
care  of  patients  in,  465 
changes  in  bone-marrow,  443 
in  gastrointestinal   tract, 

442 
in  heart,  443 
in  kidneys,  445 
in  liver,  442 
in  lungs,  445 

in  lymphatic  system,  440 
in  skin,  439 
in  spleen,  441 
in  tongue,  440 
chorea  after,  430 
choroiditis  in,  405 
circumoral  pallor  in,  372 
complicated  by  diphtheria,  397 
complications  of,   affecting  ali- 
mentary canal,  425 
bones,  429 
nervous  system,  428 
the  respiratory  organs, 
427 
ear,  399 
eye,  404 
heart,  406 
liver,  426 

respiratory  organs,  427 
and  sequelae,.  395 
skin,  423 
contagiousness  of  desquamating 
epithelium,  357 
of  scales,  462 
contagium,  aerial   transmission 

of,  357 
Credo's  ointment  in,  475 
deafness  after,  404 
definition  of,  341 
dermatitis  gangra;nosa  in,  424 
desquamation,  374,  448 
diagnosis,  447 

diagnostic  value  of  desquama- 
tion, 448 
of   strawberry  tongue, 
448 
diet,  465 

diphtheria,  differential  diagnosis 
of,  454 
bacilli  in  throat  in,  399 
disinfection,  465 
dissemination  of,  in  schools,  460 
drug    rashes,    differential   diag- 
nosis of,  453 
duration    of    desquamation    of, 
376 
of  quarantine  in,   461 
eczenia  after,  424 
empyema  in,  428 
exanthem  in,  373 


Scarlet  fever,  endocarditis  in,  406,  444 

enteritis  in,  426 

etiology  of,  341 

facial  palsy  in,  403 

family  predisposition  to,  349 

fever  in,  366 

furuncles  in,  425 

gangrene  in,  422 
of  neck  .in,  385 

gangrenous  angina  in,  396 

hemiplegia  in,  428 

hemorrhagic,  387 

hemorrhage     from     erosion     of 
bloodvessels,  409 

herpes  in,  424 

history  of,  341 

hot  pack  in,  472 

hydrotherapy  in,  467 

hygiene  of  sick  apartments  in, 
463 

hyperpyrexia  in,  368 

hypodermoclysis  in,  474 

immunity  and  susceptibility  to, 
345 

incubation  period  of,  363 

infection  in  milk,  357 

influence  of  pregnancy  and  puer- 
perium,  359 
of  race,  353 

influenza,  differential   diagnosis 
of,  454 

insanity  after,  429 

irregular,  388 

isolation  of,  460 

itching  in,  373 

involvement  of  antrum  of  High- 
more  in,  444 

jaundice  in,  426 

keratitis  i.n,  404 

kidney  changes  in,  445 

laryngitis  in,  380 

leukocytosis  in,  437 

lymphatic  glands  in,  378 

malignant,  385 

mastoid  disease  in,  403 

measles,  differential  diagnosis  of, 
453 

membranous  angina  in,  396 

meningitis  in,  403,  428 

mode   of   transmission   of   con- 
tagium, 344 

morbid  anatomy  of,  439 

multiple  neuritis  in,  429 

myocarditis  in,  406 

noma  in,  422 

oedema  of  lungs  in,  427 

optic  neuritis  in,  406 

orbital  cellulitis  in,  405 

otitis  media  in,  400 

paraplegia  in,  429 

partial  eruptions,  389 

pathology  of,  436 

pericarditis  in,  444 

period  of  infectivity  of,  355 

phlebitis  in,  425 

pleurisy  in,  428 


INDEX 


777 


SoaTlcl.  I'(!vcr,  prKMinifniiji  in,  .'Wl,  427 
\.nv.\i\\('.nw.  <»r,  iiifliic'dcc,  of  ulM- 
l,u(l<^  on,  '.Wl 
ol'  cliiii.'U.t!  on,  .'M!) 
ol'  Jocniil.y  on,  1352 
of  a(!ii.son  on,  '.ihO 
prognosis  oF,  457 
prognostic  infliuincc  of  age,  458 
ol'  (;oinj)lic!il.ion,s,  459 
ol'  viruldiicy,  45S 
prophylaxis  ol',  45!> 
protozoa  in,  'V,V,i 
puerperal,  359 

purpura  heinorrJiagica  in,  420 
rccurronces  of,  393 
relapses  of,  393 
respiratory  symptoms,  380 
return  cases  of,  356,  4()1 
rubella,  differential  diagnosis  of, 

454 
second  attacks  of,  392 
secondary  angina  in,  397 
septicitniia  and  otitis  media  in, 

401 
septic  erythema  in,  391 

form  of,  382 
sequelae  of,  430 
serotherapy  in,  374 
simplex,  365 
smallpox,  differential  diagnosis 

of,  454 
stage  of  eruption,  369 

of  invasion,  365 
strawberry  tongue  in,  448 
streptococcus,  434 
suppurative  arthritis,  420 
surgical,  361 

symptomatology  of,  363 
symptoms,  gastrointestinal,  381 

respiratory,  380 

throat,  369 
synonyms  of,  341 
tetany  in,  429 
thrombosis  of  lateral  sinus  in, 

403 
tongue,  374 
tonsillitis,  differential  diagnosis 

of,  454 
treatment  of,  374 

of  ears,  470 

of  enlarged  glands,  469 

of  fever,  467 

of  gastroiiitestinal  tract,  473 

of  heart,  473 

of  joints,  471 

of  Ludwig's  angina,  470 

medical,  467 

of  noma,  469 

of  purpura,  473 

of  purulent  rliinitis,  469 

of  throat,  468 

of  uraemia,  472 
typhoid,  387 
urticaria  in,  424 
use  of  blood  serum  of  convales- 
cents, 475 


I  Scarlet  fever  virulencf;   influenr-ing  fjrog- 
nosis,  458 
vomiting  in,  3(>(i 
vvitlioiit  angina,  392 
desquamation,  392 
eruption,  390 
fever,  388 
Scarring  after  ehiekenpox,  32(i 
Scars  after  smallpox,   190 

vaccination,  51 
Scratchy  heel,  139 
Season  and  smallpox  incidence,   154 

iiifhu^nce  of,  on  scarlet  fever,  350 
Second  attacks  of  ehiekenpox,  319 
of  measles,  485 
of  rubella,  562 
of  scarlatina,  392 
of  smallpox,  151 
Secondary  angina  in  scarlet  fever,  397 
fever  in  smallpox,  183 
toxic  or  septic  rashes  in  smallpox, 

196 
umbilication  in  smallpox,  180 
Septic  diphtheria,  629 
scarlet  fever,  382 
Septicaemia  after  vaccination,  64 

in  smallpox,  241 
Sequelae  of  cliickenpox,  329 
of  diphtheria,  640 
of  rubella,  561 
of  scarlet  fever,  395 
of  smallpox,  229 
of  typhoid  fever,  583 
Serum  treatment  of  diphtheria,  730 

of  smallpox,  306 
Sheeppox,  135 

Sheffield  smallpox  statistics,  118,  119,  121 
Ship  fever.     See  Tj-phus,  566 
Simple  scarlet  fever,  365 
Skin  complications  in  scarlet  fever,  423 
Sloughing  of  vaccine  site,  63 
Smallpox,  144 

abscesses  in,  229 

age  incidence  of,  112 

albuminuria  in,  226 

alopecia  after,  191 

in  America,  147 

atmospheric  conditions  and,  156 

bacteriologv  of,  256 

baths  in,  299 

continuous  warm,  300 
bed-sores  in,  231 
blood  in,  253 
boils  in,  229 
in  camel,  143 
carbuncles  m,  230 
changes  in  bone-marrow  in,  250 
in  heart  in.  250 
ixx  kidneys  in,  249 
in  liver  in,  249 
in  hTnphatic  glands  in,  250 
in  skin  in,  242 
in  spleen  in,  249 
in  testicles  in,  251 
complications  of  abdominal,  237 
ear,  235 


778 


INDEX 


Smallpox,  complications  of,  heart,  236 

nervous,  237 

ocular,  231 

respiratory,  236 

and  sequelae  of,  229 
confluent,  199 

superficial,  212 
conjunctivitis  in,  232 
corneal  ulcer  in,  233 
in    countries    where    vaccination    is 

neglected,  132 
critical  days  of,  279 
cytoryctes  variolse,  264 
deaths  among  royalty  from,  149 
decline  of,  after  introduction  of  vac- 
cination, 105 
delirium  in,  182 
diagnosis  of,  266 
diet  and  stimulants  in,  301 
disinfection,  285 

disseminated  spinal  sclerosis  in,  241 
dviration  of  isolation  of,  287 
effect  of  season  on,  154 
eruption   upon   mucous   membranes 

in,  180 
erysipelas  complicating,  230 
etiology  of,  150 
exfoliative  dermatitis  in,  196 
fever  in,  183 
in  foetus,  221 
gangrene  of  scrotum  in,  231 

of  skin  in,  194,  231 
hemorrhagic,  202 
incubation  period  of,   166 
infected  sick-room  objects,  160 
infection  of,  157 

carried  by  healthy  persons,  160 

transmitted  in  the  air,  161 
infectious  period,  157 
infectiousness  of  blood  in,  255 
initial  stage  of,  167 
inoculation  of,  in  America,  25 
insanity  after,  237 
insusceptibihty  to,  150 
involution  of  eruption  in,  185 
iritis  in,  235 

isolation  of  patients  in,  282 
itching  in,  189 
joint  disease  in,  237 
local  use  of  tincture  of  iodine,  311 
macules,  174 
mild  type  of,  206 
modified,  209 
in  monkey,  143 
mortality  in   prevaccination   period, 

275 
in  negroes,  154,  276 
number  of  lesions  present,   179 
oedema  of  glottis  in,  181 
orchitis  in,  237 
otitis  media  in,  235 
papules,  174 
paralysis  in,  238 
paraplegia  in,  239 
pathology  of,  242 

of  mucous  membranes,  248 


Smallpox,  peripheral  neuritis  in,  241 
phimosis  in,  237 
phlebitis  after,  237 
pigmentation  after,  190 
pleurisy  in,  236 
pneumonia  in,  236 
in  pregnant  women,  215 
prevalence   of,    before   discovery   of 

vaccination,  106 
prevention  of  pitting  in,  308 
prodromal  rashes  of,  171 
prognosis  of,  275 
prophylaxis,  282 

pseudokeloidal  growths  after,  230 
pustules,  177 
quarantine  of,  283 
rashes  in,  196 

scarlatiniform  erythema,  196 
scars  of,  190 
second  attacks  of,  151 
septicaeinia  and  pysemia  in,  241 
in  sheep,  135 
sore  throat  in,  181 
stage  of  decrustation,  186 
of  desiccation,  185 
of  eruption,  173 
of  suppuration,  176 
streptococcus  pyogenes  in,  261 
symptomatology  of,  166 
symptoms,  favorable,  281 

unfavorable,  281 
toxic  or  septic  rashes,  196 
treatment  of,  282 

of  eye  complications,  313 
local,  306 

of  nervous  svmptoms,  297 
red  light,  304 
serum,  306 
of  throat,  297 
urine  in,  171,  225 
use  of  morphine  in,  298 
vaccinated  and  unvaccinated,  116 
vaccination  during  the  incubation  of, 

290 
varieties  of,  199 
vesicles,  174 
Sore  throat  in  smallpox,  181 
Spontaneous  cowpox,  142 

at  Cohasset,  93 
Spotted  fever.     See  Typhus,  566 
Spurious  vaccination,  42,  49 
Stage  of  decrustation  in  smallpox,  186 

of  desiccation  in  smallpox,  185 
Statistical   evidence   of   efficacy   of   vac- 
cination, 105 
Statistics  of  the  German  Vaccination  Law, 
123 
of  revaccination,  120 
of   smallpox   mortality   before    and 
after  introduction  of  vaccination, 
108 
Strawberry    tongue     in     scarlet     fever, 

374 
Streptococcus      pyogenes    in    smallpox, 
261 
in  scarlet  fever,  434 


INDEX 


779 


Siilplmr  (linxidc  (liHiiii'cctJoii,   7(»;i 

inclliod   of,    IM 
(Siipixinilivc   lever  in   ,sin;ill|)o\,    \K', 

.sl.'ifie  ol'  sMi.'illpox,    I7(> 
Siir^ie.'il  se.'irlel.  lexer,  ;',(il 
Siiseepliliilily  to  VMceiiii.'M)!'  irifjirirs  horn 

of  \;ifi()l()iis  niolliers,  221 
Sweden,    iiil  i-()diiei'ioii    of    \;icein;il  ion    in, 
107 
v;icein;ition     made     eoinpnlsory     in, 

107 
smallpox    (leaXlis    before    and    after 
introduction  of  vaccination,  11 
Symptomatoloify  of  cliici<enj)ox,  821 
ol"  diplitiieria,  ()22 
of  measles,   187 
of  rubella,  550 
of  scarlet  fever,  303 
of  smallpox,  KiO 
of  lypluis  fever,  575 
Synonyms  of  measles,  476 

of  scarlet  fever,  341 
Syno\'itis  scarlatinosa,  419 
Syphilis  following  vaccination,  70 


TARDY  vaccinia,  38 
Tetanus   germs  in  vaccine  lymph, 
102 
after  vaccination,  73 
Third  attacks  of  measles,  486 
Toxic  rashes  in  smallpox,  196 
Tracheotomy  in  diphtheria,  727 
Transmission  of  scarlet  fever  contagiimi, 
344 
of  smallpox  infection  in  the  air,  161 
by  domestic  animals,  165 
by  insects,  105 
Trituration  of  vaccine  pulp,  104 
Treatment  of  chickenpox,  339 
of  diphtheria,  687 
of  measles,  535 
of  scarlet  fever,  459 
of  smallpox,  282 
of  typhus  fever,  592 
Tuberculosis  after  vaccination,  78 
Typhoid  scarlatina,  387 
Typhus  fever,  506 

age  factor  in  prognosis,  589 

incidence,  571 
alcohol  in,  596 
bacteriology  of,  572 
bed-sores  in,  583 
boils  in,  584 
bronchitis  in,  582 
changes  in  blood  in,  574 

in    carcUovascular    system, 

in,  574 
in  digestive  tract  in,  575 
in  kidneys  in,  575 
in    respiratorv    organs    in, 
574 
comphcations   and   sequela;   of, 

583 
contagiousness  of,  569 
contagious  period,  570 


Typlms  fever,  deafncsH  in,  582 
definition,  500 
delirium  in,  581 

tremens,   difTen-iitiai    <Jiaf^- 
nosJH  of,  5SS 
<liagnosis  of,  580 
diet  in,  594 
disinfection  in,  593 
durat  ion  of,  5H4 
eniption  in,  579 
erysipelas  in,  584 
etiology  of,  508 
exant  hem,  579 
l'e\cr  in,  577 
gangrene  in,  584 
geographical  distribution  of,  580 
hcmorrliagic  form  (jf,  585 
history  of,  506 

hygienic  environment  and  prog- 
nosis of,  590 
infection,  aerial  transmission  of, 

571 
insanity  after,  584 
intemperance  and  prognosis  of, 

590 
isolation  of,  593 
jaundice  in,  584 
kidneys  in,  583 
laryngitis  in,  583 
lymphatic  glands  in,  580 
malaria,  differential  diagnosis  of, 

587 
measles,  differential  diagnosis  of, 

588 
meningitis  and  diagnosis  of,  587 
mode  of  dissemination  of  con- 

tagium,  570 
mortality  rate  of,  592 
nursing  of,  594 
parotitis  in,  584 
pathology  of,  573 
period  of  incubation  of,  575 
pneumonia  in,  583 

diagnosis  of,  588 
predisposing  causes  of,  571 
prognosis  of,  589 
prophylaxis  of,  592 
pulse  in,  578 
purpura,    differential    diaenosis 

of,  588 
relapsing       fever,       differential 

diagnosis  of,  587 
sine  exanthemate,  580 
smallpox,  differential   diagnosis 

of,  588 
spleen  in,  580 
sraiptomatology.  575 
symptoms  favorable,  591 
gastrointestinal,  582 
nervous,  581 
respiratorA",  582 
unfavorable,  591 
sjTionyms,  566 
treatment  of.  592 

of  digestive  tract,  596 
of  fever,  595 


780 


INDEX 


Typhus   fever,    treatment   of    fever    in, 
medical,  595 
of  nervous  symptoms,  595 
typhoid  fever,  differential  diag- 
nosis of,  586 
ventilation  in,  594 


UMBILICATION  in  smallpox,  174, 244, 
247 
secondary,  186 
Ursemia  in  scarlet  fever,  417 
Urine  in  smallpox,  ]71,  225 
Urticaria  complicating  vaccination,  70 


VACCINAL  complications,  58  . 
eczema,  80 

eruptions,  60 

erysipelas,  72 

erythema,  68 

gangrene,  67 

injuries,  58 

insusceptibility,  43 

leprosj^,  79 

lichen,  68 

miliaria,  69 

psoriasis,  82 

roseola,  68 

scars,  size,  53 

syphilis,  76 

tetanus,  73 

tuberculosis,  78 

ulceration,  64 
Vaccination,  30 

advantages  of  animal,  94 

asepsis,  33 

of  calf,  103 

of  calves,  93 

cellulitis,  63 

contraindications  to,  32 

dermatitis  gangrsenosa  infantum  in, 
68 

disinfection  of  skin  before,  33 

during  incubation  of  smallpox,  290 

glandular  abscesses  in,  67 

hypodermic  puncture  in,  33,  34 

introduction  of,  in  Sweden,  107 

laws  in  Germany,  123 

number  of  insertions  in,  34 

opponents  of,  114 

opposition  to,  134 

proper  age  for,  32 

as  prophylactic  measure,  288 

roseola  vaccinosa,  37 

sanitation  in  Glasgow  and,  116 

shields,  34 

statistical  evidence  of  efficacy,  105 

"  sore  arm,"  62 

technique  of,  32,  33 
Vaccine,  30 

condition  of,  31,  32 

famine,  96 

lymph,  glycerinated,  97 
natural  sources  of,  91 

propagation,  103 


Vaccine  virus,  actinomyces  in,  103 

bacteriological     impurities     of, 

102 
tetanus  germs  in,  102 
Vaccinia,  17 

accessory  vesicles,  41 
Bryce's  test,  41 
in  cow,  142 
excrescence,  42 
gangrsenosa,  67 
general  isata,  60 
hemorrhagica,  63 
protozoa  in,  62 
symptoms  and  course,  35 
supernumerary  vesicles,  41 
Vaccinoid,  47,  48 
Varicella,  316 

in  adults,  327 
blood  in,  335 

complications  and  sequelae  of,  329 
diagnosis  of,  335 
eruptive  stage  of,  322 
erysipelas  complicating,  330 
etiology  of,  318 
gangrsenosa,  330 
history  of,  316 
incubation  period  of,  320 
nephritis  in,  332 
pathology  of,  334 
prodromal  erythema,  322 
prognosis  of,  339 
pyaemia  complicating,  330    . 
scarring  after,  326 
second  attacks  of,  319 
symptomatology  of,  321 
synovitis  and  arthritis  in,  331 
treatment  of,  339 
Variola,  145 

abscesses  in,  229 
age  incidence  of,  112 
albuminuria  in,  226 
alopecia  after,  191 
bacteriology  of,  256 
baths  in,  299 

continuous  warm,  299 
bed-sores  in,  231 
benigna,  209 
blood  in,  253 
boils  in,  229 
carbunculosa,  213 
carbuncles  in,  230 
changes  in  bone-marrow  in,  250 

in  heart  in,  250 

in  kidneys  in,  249 

in  liver  in,  249 

in  lymphatic  glands  in,  250 

in  skin  in,  242 

in  spleen  in,  249 

in  testicles  in,  251 
comphcations  of,  abdominal,  237 

ear,  235 

eye,  231 

heart,  236 

nervous,  237 

respiratory,  236 

and  sequelae  of,  229 


INDEX 


781 


Vitriol!!,,  oonfliiont,,  W.) 
coiiicii,  2i;i 
conjuri(;l,ivil,i.s  in,  232 
corn(!ii,  21.'i 
corncijiJ  nicer  in,  2l{;i 
coryiiihoH.'i,  2i;5 
criUc,;i.l  diiy.s  of,  279 
cry.s(,;iliin;i,,  '2\',i 
doliriuiii  in,  1S2 
<liiifi;n()si.s  ol',  2(K) 
diet  and  .slimidiuiis  in,  '.Wi 
disinl'eelion,  2,Sr) 

disseniinuted  spinal  sclerosis  in,  241 
dnration  of  isolation  of,  287 
e(|nin;e,  l.'iS 
eruption  upon  mucous  membranes, 

180 
erysipelas  complicating,  230 
etiology  of,  150 
exfoliative  denriatitis,  196 
foetus  in  the,  221 
fever  in,  183 
fimbriata,  213 

gangrene  of  skin  in,  194,  231 
globulosa,  213 
hemorrhagic,  202 
incubation  period  of,  166 
infectious  period,  157 
infectiousness  of  blood  of,  255 
initial  stage  of,  167 
insanity  after,  237 
insusceptibility  to,  150 
involution  of  the  eruption,  185 
iritis  in,  235 

isolation  of  patient,  282 
itching  in,  189 
joint  disease  in,  237 
local  use  of  tincture  of  iodine,  311 
lymphatica,  213 
miliaris,  213 
modificata,  209 
in  monkey,  143 
morbillosa,  213 
nigra,  204 

number  of  lesions  present,  179 
orchitis  in,  237 
otitis  media  in,  235 
Ovina,  135 
paralysis  in,  238 
paraplegia  in,  239 
pathology  of,  242 
of  mucous  membranes,  248 
pemphigosa,  213 
peripheral  neuritis  in,  241 
phimosis  in,  237 
phlebitis  after,  237 
pigmentation  after,  190 
pleurisy  in,  236 
pneumonia  in,  236 
pregnant  women  in,  215 
prevention  of  pitting,  30S 
prodromal  rashes,  171 
prognosis  of,  275 
prophylaxis,  282 


Variola,  protozoa  in,  2f»2 

pseudokfiloidjil  growths  after,  230 

purfnirica,  203 

pnstulariH,  2)3 

pustnlosa  hemorrhagica,  205 

quarantine,  283 

rosea,  213 

Hcarlatiniforrn  erythema,  196 

s(!ars  aft('r,  1 90 

septic  or  toxic  rashes,  196 

septiciemia  and  j)yEernia,  241 

silifiuosa,  213 

sine  exanthemate,  172,  212 

variolis,  212 
sore  throat  in,  181 
stage  of  decrustation,  186 
desiccation,  185 
eruption,  173 
of  suppuration,  176 
streptococcus  pyogenes  in,  261 
symptomatology  of,  166 
symptoms  favoral)le,  281 

unfavorable,  281 
treatment  of,  282 

of  eye  complications,  313 
of  nervous  s^'mptoms,  297 
red  Hght,  304 
serum,  306 
of  throat.  297 
local,  306 
urine  in,  171,  225 
use  of  morphine,  298 
vaccination  during  incubation  period 

of,  290 
varieties  of,  199 
varioloid    and    comparative    death 

rates  of,  278 
verrucosa,  213 
Variote  vaccinse,  17 
Varioloid,  209 

hemorrhagic,  206 

and  variola,  comparative  death  rates, 
278 
Variolation  of  bo^dne  animals,  87 
Variolous  diseases  of  lower  animals,  135 
impetigo,  192 
infection    transmitted    in    the    air, 

161 
macules,  174 
papules,  174 
pustules,  177 
roseola,  171 
in  scarlet  fe^-er,  370 
vesicles,  174 
Virus,  glycerinated,  97 

preparation  of  glycerinated,  103 
Vomiting  in  scarlet  fe^"e^,  366 


WALDHEIM  smallpox  statistics,  118 
Warrington   smallpox    statistics, 
113,  lis,  121 
Wartpox,  213 
Woodville's  lymph,  91 


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Demco,  Inc.  38-293                                                        ' 

